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A high fat diet rich in corn oil reduces spontaneous locomotor activity and induces insulin resistance in mice
... In contrast, the signaling pathway, Janus kinase/signal transducer and activator of transcription (JAK/STAT), was shown to be a master signaling pathway that is activated during cardiac fibrosis and remodeling. Indeed, the JAK/STAT pathway has been shown to be over-activated in fibrotic hearts of various models of CVD including those under pressure overload and induced-ischemia, myocardial infarction (MI), heart failure (HF), and diabetes mellitus (DM) (Boengler, Hilfikerkleiner, Drexler, Heusch, & Schulz, 2008;Liu et al., 2018;Mascareno et al., 2001;Modesti et al., 2005;Wang, Shaw, Amiri, Eaton, & Marrero, 2002;Wong, et al., 2015). The JAK/STAT family includes JAK1-3 and STAT1-4, STAT5a, STAT5b, and STAT6, all of which have been observed in the mammalian's heart or neonatal ventricular myocytes (Booz, Day, & Baker, 2003). ...
... Angiotensin, corn oil, fibrosis, heart, high-fat diet, JAK/STAT oxidative stress and inflammation (Abbey et al., 1993;Calder, 2004;Gurr, 2012;Louheranta, Porkkala-Sarataho, Nyyssönen, Salonen, & Salonen, 1996;Okuyama, Fujii, & Ikemoto, 2001;Wong et al., 2015). ...
... Hyperglycemia, hyperinsulinemia, ROS, and IL-6 are potent enhancer of ANGII/JAK/STAT pathway and cardiac fibrosis in the heart of animal models, in vivo, and stimulate CFs differentiation and collagen synthesis in vitro (Meléndez et al., 2010;Modesti et al., 2005;Nickenig, Röling, Strehlow, Schnabel, & Böhm, 1998;Samuelsson et al., 2006;Wong, et al., 2015). ...
This study compared the effect of low‐fat diet (LFD) and high‐fat diet rich in corn oil (HFD‐CO) on left ventricular (LV) fibrosis in rats and examined their effect of angiotensin II (ANG II), JAK/STAT, and TGF‐1β/smad3 pathways. As compared to LFD which didn't affect any of the measured parameters, HFD‐CO‐induced type 2 diabetes phenotype and increased LV collagen synthesis. Mechanistically, it increased LV levels of ROS, ANG II, ACE, IL‐6, s‐IL‐6Rα, TGF‐β1, Smad‐3, and activities of JAK1/2 and STAT1/3. AG490, a JAK2 inhibitor, partially ameliorated these effect while Losartan, an AT1 inhibitor completely abolished collagen synthesis. However, with both treatments, levels of ANG II, IL‐6, and s‐IL‐6Rα, and activity of JAK1/STAT3 remained high, all of which were normalized by co‐administration of NAC or IL‐6 neutralizing antibody. In conclusion: HFD‐CO enhances LV collage synthesis by activation of JAK1/STAT3/ANG II/TGF‐1β/smad3 pathway.
Practical applications
We report that chronic consumption of a high‐fat diet rich in corn oil (HFD‐CO) induces diabetes mellitus phenotype 2 associated with left ventricular (LV) cardiac fibrosis in rats. The findings of this study show that HFD‐CO, and through the increasing generation of ROS and IL‐6 levels and shedding, could activate LV JAK1/2‐STAT1/3 and renin‐angiotensin system (RAS) signaling pathways, thus creating a positive feedback between the two which ultimately leads to activation of TGF‐1β/Smad3 fibrotic pathway. Herein, we also report a beneficial effect of the antioxidant, NAC, or IL‐6 neutralizing antibody in preventing such adverse effects of such HFD‐CO. However, this presents a warning message to the current sudden increase in idiopathic cardiac disorders, especially with the big shift in our diets toward n‐6 PUFA.
... We reported recently that in Canada, increases in dietary fat between the 1970's and 2000's are attributable to increased consumption of monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA) but not saturated fatty acids (SFA) [4]. Indeed, to protect against cardiovascular diseases, SFA has been deliberately removed from our food supply in favour of MUFA and PUFA [5][6][7]. ...
... PLOS [26,27]. In basic research, we also demonstrated significant loss of spontaneous activity and elevated insulin resistance in mice fed PUFA diets irrespective of either total food intake or body weight [4]. Therefore, we focussed our analysis to the female sex, taking advantage of published data concerning European females from across Europe. ...
... Norway was removed as an outlier. promotes loss of spontaneous activity and insulin resistance in mice [4]. Most interestingly, it has been demonstrated that muscle phospholipid n-6 PUFA content increases with a sedentary profile even in healthy humans [49]. ...
In recent years, dietary polyunsaturated fatty acids (PUFA) have increased in parallel to sedentary behavior and diabetes across the world. To test any putative association between dietary PUFA and sedentary behavior or diabetes in females, we obtained country-specific, cross-sectional data on sedentary activity and diabetes prevalence from European Cardiovascular Statistics 2012. Age and gender-specific, nutritional data from each country were obtained from nutritional surveys as well. Socioeconomic (GDP), physical environment (urbanization index) and climatic confounders were accounted for each country. Upon analysis, we found a strong, positive association between sedentary lifestyle in 11-yr old girls (> = 2 hours of TV/ weekday) and dietary PUFA across 21 European countries. Further, a weak association of dietary PUFA and a strong relationship of per-capita GDP was established with elevated fasting blood glucose [(> = 7.0 mmol/L; or on medication] among 25+ year old adult females across 23 countries in Europe. In summary, we present novel ecological evidence that dietary PUFA is strongly associated with sedentary behavior among pre-teen girls and weakly associated with diabetes among adult women across Europe. In the latter group, per-capita GDP was a significant predictor for diabetes as well. Therefore, we recommend that prospective randomized controlled trials (RCTs) be implemented to evaluate if ubiquitous presence of dietary PUFA and low socioeconomic status are possible confounders when intervening to treat/prevent sedentary lifestyle or diabetes in female subjects in Western nations.
... The intake of a diet rich in fat has been associated with a higher prevalence of obesity (Bray et al., 1981;Flatt, 1988), which is accompanied by behavioral changes including an increase in ingestive behavior (Warwick et al., 2003;Chang et al., 2004) and a reduction in spontaneous, overall locomotor activity (Barzel et al., 2015;Wong et al., 2015). Studies in the hypothalamus, a brain region involved in controlling food intake, energy balance, and related behaviors, have identified in animals a variety of orexigenic neuropeptides which mediate these behaviors affected by a fat-rich diet. ...
... In adult animals, central injection of these neuropeptides or their analogs stimulates preferential intake of a high-fat diet (HFD) (Robert et al., 1989;Kyrkouli et al., 1990a,b;Gomori et al., 2003;Naleid et al., 2007), and HFD intake in turn increases the expression and levels of these orexigenic neuropeptides in the PVN and PFLH (Akabayashi et al., 1994;Elliott et al., 2004;Chang et al., 2007;Gaysinskaya et al., 2007), suggesting that they function within a positive feedback circuit to promote excess consumption. Administration of these neuropeptides also induces changes in locomotor behavior, with subcutaneous or intracerebral injection of an ENK analog found to depress locomotor activity (Bhargava, 1978;Szekely et al., 1980), similar to an effect produced by the consumption of a HFD (Novak et al., 2010;Wong et al., 2015). This positive relationship of these neuropeptides in the PVN and PFLH to dietary fat is very different from that seen in the hypothalamic arcuate nucleus (ARC), where another orexigenic peptide, neuropeptide Y (NPY), is reduced by intake of a HFD and positively associated with ingestion of a carbohydrate-rich diet (Stanley et al., 1985;Jhanwar-Uniyal et al., 1993;Brown et al., 1998). ...
... With the ingestion of a HFD known to reduce locomotor behavior (Barzel et al., 2015;Wong et al., 2015) and our results revealing molecular and behavioral effects of CXCL12 that are similar to those of a HFD, we investigated whether this chemokine also affects locomotor behavior in a manner similar to a HFD. The results of the present study support this idea, confirming that intake of a HFD for 5 days reduces locomotor activity in a novel open field, as previously shown (Barzel et al., 2015;Wong et al., 2015), and also demonstrates that central administration of CXCL12 similarly decreases noveltyinduced locomotor activity. ...
The intake of a high fat diet (HFD), in addition to stimulating orexigenic neuropeptides in the hypothalamus while promoting overeating and reducing locomotor behavior, is known to increase inflammatory mediators that modulate neuronal systems in the brain. To understand the involvement of chemokines in the effects of a HFD, we examined in rats whether HFD intake affects a specific chemokine, CXCL12, and its receptors, CXCR4 and CXCR7, in the hypothalamus together with the neuropeptides and whether CXCL12 itself acts similarly to a HFD in stimulating the neuropeptides and altering ingestion and locomotor behavior. Compared to low-fat chow, a HFD for 5 days significantly increased the expression of CXCL12 and its receptors, in both the paraventricular nucleus (PVN) where the neuropeptides enkephalin (ENK) and galanin were also stimulated and the perifornical lateral hypothalamus (PFLH) where orexin (OX) and melanin-concentrating hormone (MCH) were increased. In contrast, the HFD had no impact on expression of CXCL12 or its receptors in the arcuate nucleus (ARC) where the carbohydrate-related peptide, neuropeptide Y (NPY), was suppressed. Analysis of protein levels revealed a similar stimulatory effect of a HFD on CXCL12 levels in the PVN and PFLH, as well as in blood, and an increase in the number of CXCR4-positive cells in the PVN. In the ARC, in contrast, levels of CXCL12 and number of CXCR4-positive cells were too low to measure. When centrally administered, CXCL12 was found to have similar effects to a HFD. Injection of CXCL12 into the third cerebral ventricle immediately anterior to the hypothalamus significantly stimulated the ingestion of a HFD, reduced novelty-induced locomotor activity, and increased expression of ENK in the PVN where the CXCR4 receptors were dense. It had no impact, however, on NPY in the ARC or on OX and MCH in the PFLH where the CXCR4 receptors were not detected. These results, showing CXCL12 in the hypothalamus to be stimulated by a HFD and to mimic the effects of the HFD where its receptors are located, suggest that this chemokine system may have a role in mediating both the neuronal and behavioral effects induced by a fat-rich diet.
... In previous studies, we have shown that gut health influences the immune-metabolic system, and that the gut microbiome is adversely affected with corn oil diets rich in omega-6 polyunsaturated fatty acids [71][72][73][74]. In a recent study, we demonstrated that consumption of corn oil led to metabolic dysfunction and insulin resistance in mice compared to the beneficial olive oil [75]. In parallel, we have shown that this exact diet also promotes intestinal barrier dysfunction and systemic chronic inflammation associated with colitis [73]. ...
... Mice exposed to either high-fat or high-sugar diets have reduced SCFA [206]. Our group [75] and many other groups [207] have demonstrated the role of HFD on stimulating metabolic disorders such as NAFLD, CVD and diabetes. HFD disrupts the shape of intestinal bacteria, as a result of reducing SCFA production and increasing gut permeability [206,208]. ...
The role of the microbiome in health and disease has gained considerable attention and shed light on the etiology of complex diseases like inflammatory bowel disease (IBD) and metabolic syndrome (MetS). Since the microorganisms inhabiting the gut can confer either protective or harmful signals, understanding the functional network between the gut microbes and the host provides a comprehensive picture of health and disease status. In IBD, disruption of the gut barrier enhances microbe infiltration into the submucosae, which enhances the probability that gut-derived metabolites are translocated from the gut to the liver and pancreas. Considering inflammation and the gut microbiome can trigger intestinal barrier dysfunction, risk factors of metabolic diseases such as insulin resistance may have common roots with IBD. In this review, we focus on the overlap between IBD and MetS, and we explore the role of common metabolites in each disease in an attempt to connect a common origin, the gut microbiome and derived metabolites that affect the gut, liver and pancreas.
... Feeding influences energy homeostasis primarily due to its effect on energy intake. However, nutrients and the caloric content of the diet can also affect SPA and, consequently, energy expenditure 24,25 . As diet modification, both in terms of calorie density and also macronutrients, is a common tool to promote body weight loss, a more comprehensive view of how dietchanging can affect total daily energy expenditure is of great importance. ...
... The deleterious peripheral and central effects of high-fat diet are well established 26,27 . Interestingly, high-fat diet has also been shown to decrease spontaneous physical activity in rodents 18,24 . This effect could be seen as early as after a few hours on the diet, and it remained throughout the 21 days in which mice received the diet rich in fat 18 . ...
Spontaneous physical activity (SPA) consists of all daily living activities other than volitional exercise (e.g. sports and fitness-related activities). SPA is an important component of energy expenditure and may protect from overweight and obesity. Little is known about the biological regulation of SPA, but animal researchhas contributedsignificantly to expand our knowledge in this field. Studies in rodents have shown that SPA is influenced by nutrients and volitional exercise. High-fat diet seems to decrease SPA, which contributes to weigh gain. Volitional exercisemayalso reduce SPA, helping to explain the commonly reported low efficiency of exercise to cause weight loss, and highlighting the need to finda volume/intensity of exercise to maximize total daily energy expenditure. Animal studieshave also allowed for the identification of some brain areas and chemical mediatorsinvolved in SPA regulation. These discoveries could enable the development of new therapeutics aiming to enhance SPA.
... On one hand, data shows linoleic acid may improve insulin sensitivity by activating the Akt and AMP-activated protein kinase signalling pathways [52]. However, corn oil (rich in linoleic acid) can induce insulin resistance, in mice, via a lack of muscle peroxisome proliferatoractivated receptor activation, and linoleic acid can induce inflammation, via lipid-mediated mechanisms [53], potentially leading to insulin resistance [54]. Importantly, the ratio of n-6 to n-3 fatty acids may also be of significance [55]. ...
High carbohydrate, lower fat (HCLF) diets are recommended to reduce cardiometabolic disease (CMD) but low carbohydrate high fat (LCHF) diets can be just as effective. The effect of LCHF on novel insulin resistance biomarkers and the metabolome has not been fully explored. The aim of this study was to investigate the impact of an ad libitum 8-week LCHF diet compared with a HCLF diet on CMD markers, the metabolome, and insulin resistance markers. n = 16 adults were randomly assigned to either LCHF (n = 8, <50 g CHO p/day) or HCLF diet (n = 8) for 8 weeks. At weeks 0, 4 and 8, participants provided fasted blood samples, measures of body composition, blood pressure and dietary intake. Samples were analysed for markers of cardiometabolic disease and underwent non-targeted metabolomic profiling. Both a LCHF and HCLF diet significantly (p < 0.01) improved fasting insulin, HOMA IR, rQUICKI and leptin/adiponectin ratio (p < 0.05) levels. Metabolomic profiling detected 3489 metabolites with 78 metabolites being differentially regulated, for example, an upregulation in lipid metabolites following the LCHF diet may indicate an increase in lipid transport and oxidation, improving insulin sensitivity. In conclusion, both diets may reduce type 2 diabetes risk albeit, a LCHF diet may enhance insulin sensitivity by increasing lipid oxidation.
... In addition, the olfactory cues and the oily texture of corn oil are important orosensory factors provoking a strong appetite in mice [57]. However, other reports showed that the excess dietary intake of polyunsaturated fatty acids is associated with loss of spontaneous physical activity and development of insulin resistance [58]. In addition, polyunsaturated fatty acids are subject to oxidation. ...
The laboratory mouse is the most common used mammalian research model in biomedical research. Usually these animals are maintained in germ-free, gnotobiotic, or specific-pathogen-free facilities. In these facilities, skilled staff takes care of the animals and scientists usually don’t pay much attention about the formulation and quality of diets the animals receive during normal breeding and keeping. However, mice have specific nutritional requirements that must be met to guarantee their potential to grow, reproduce and to respond to pathogens or diverse environmental stress situations evoked by handling and experimental interventions. Nowadays, mouse diets for research purposes are commercially manufactured in an industrial process, in which the safety of food products is addressed through the analysis and control of all biological and chemical materials used for the different diet formulations. Similar to human food, mouse diets must be prepared under good sanitary conditions and truthfully labeled to provide information of all ingredients. This is mandatory to guarantee reproducibility of animal studies. In this review, we summarize some information on mice research diets and general aspects of mouse nutrition including nutrient requirements of mice, leading manufacturers of diets, origin of nutrient compounds, and processing of feedstuffs for mice including dietary coloring, autoclaving and irradiation. Furthermore, we provide some critical views on the potential pitfalls that might result from faulty comparisons of grain-based diets with purified diets in the research data production resulting from confounding nutritional factors.
... By the end of week 8, All rats were fasted on two separate days (12 h) and then exposed to either OGTT (oral glucose tolerance test; 2 g/kg) or IPITT (intraperitoneal insulin tolerant test; 0.75 units/kg) as described by others (Wong et al., 2015). In both cases, a blood sample (250 ml) were collected by cutting the tail, at 0.0, 15, 30, 60, and 120 min, in EDTA (10 ml of 10% of K3-EDTA/ml blood) Eppendorf tubes, centrifuged at 1000 Â g for 5 min to collect plasma. ...
This study examined if the Fisetin against streptozotocin-induced diabetic cardiomyopathy (DC) in rats involves regulating cardiac metabolism and suppressing protein kinase R (PKR). Male rats were divided (12/groups) as control (non-diabetic), control + Fisetin, T1DM, and T1DM + Fisetin. Fisetin was administered orally at a final dose of 2.5 mg/kg for 12 weeks. In T1DM1-induced rats, Fisetin prevented heart and final body weights loss, lowered circulatory levels troponin I and creatinine kinase-MB (CK-MB), increased fasting insulin levels, and improved ventricular systolic and diastolic functions. It also preserved the structure of the cardiomyocytes and reduced oxidative stress, fibrosis, protein levels of transforming growth factor-β1 (TGF-β1), collagenase 1A, caspase-3, and the activation of JNK, p53, and p38 MAPK. In the control and diabetic rats, Fisetin attenuated fasting hyperglycaemia, the increases in glucose levels after the oral and insulin tolerance tests, and HOMA-IR. It also increased cardiac glucose oxidation by increasing the activity of private dehydrogenase (PDH), phosphofructokinase (PFK), protein levels of PPAR-α and suppressed cardiac inflammation by inhibiting NF-κB. These effects were associated with a reduction in the activity of PKR and subsequent increase in the activity of eeukaryotic initiation factor 2 (eIF2) with a parallel increase in protein levels of p67, a cellular inhibitor of PKR. In cultured cardiomyocytes, Fisetin, prevented high glucose (HG)-induced activation of PKR and reduction in p67, in a dose-dependent manner. However, the effect of Fisetin on PKR was diminished in LG and HG-treated cardiomyocytes with p67-siRNA. In conclusion, Fisetin protects against DC in rats by improving cardiac glucose metabolism and suppressing PKR.Saudi Pharmaceutical Journal
... By the end of week 8, oral glucose tolerance test (OGTT) or intraperitoneal insulin tolerant test (IIPTT) were conducted as described by Wong et al. (2015) using single administration of oral glucose solution (2 g/kg) and i.p. administration of insulin (0.75 units/kg) conducting on two different days on 12-h fasted rats. In both tests, blood samples (350 ml) were collected form the tail at different time intervals (0.0, 15, 30, 60, and 120 min) in EDTA containing tubes to collect plasma (1000 Â g for 5 min). ...
This study examined the impact of different cooking methods on fatty acid (FAs) composition of shrimp meat and the ability of these foods to protect against high cholesterol (HC) diet-induced non-alcoholic fatty liver disease (NAFLD) in rats. Shrimp were cooked for 10 min boiled, grilled, or fried in sunflower oil. Rats (n = 6/group) were fed a normal diet (ND)or high-cholesterol diet (HC) each containing boiled, grilled or fried shrimp powder (15% w/w) (NDBS, NDFS, NDGS for ND or HCBS, HCFS, HCDGS for HC diet). Frying alone significantly reduced total levels of saturated FAs (SFA) and increased total mono- and polyunsaturated FAs (MSFA, and PUFAs, respectively) in shrimp meat. It also increased levels of n-6 PUFAs and linoleic acid (LA) and decreased levels of n-3 PUFAs including eicosapentaenoic FAs (EPA) and docosahexaenoic fatty acid (DHA). When fed to HC rats, only diets containing the grilled and boiled shrimp powders significantly prevented the weight loss, lowered fasting and glucose levels, improved glucose and insulin tolerance, and prevented the increase in serum liver markers, ALT and AST. They also reduced hepatic fat accumulation, reduced serum levels and hepatic levels of cholesterol and triglycerides (TGs), reduced hepatic levels of MDA, tumor necrosis factor-alpha (TNF-α), and IL-6, and increased those of glutathione (GSH) and superoxide dismutase (SOD). No alterations in all these parameters were observed in HC-fed rats which fed fried shrimp. In conclusion, boiling and grilling but not frying are the best method to cook shrimp to preserve their fatty acid content and its nutritional value in ameliorating NAFLD.
... At the level of the brain different alterations ranging from a dysregulation of the normal levels of NPY, 5-HT and DA among others have been shown to occur Karin Eva Koopman, Booij, Fliers, Serlie, & la Fleur, 2013;Pritchet & Hajnal, 2011). The effects of a hyper caloric diet on the rhythmicity and the expression of clock genes has been reported in peripheral organs such as the liver and adipose tissue with varying effects depending on the energy content of the diet, the age and species of the animals used in the studies as well as the duration of the diet (Branecky et al., 2015;Cunningham et al., 2016;Pendergast et al., 2013;Wong et al., 2015). Few studies have focused on the effects of a diet-induced obesity (DIO) on the rhythmic expression of neuropeptides and clock-genes in the brain. ...
This thesis studied the interaction between diet-induced obesity and the 24h variations in behavior and physiology paced by the circadian system. Mice and rats were fed with a free choice high-fat high-sugar diet (fcHFHS). In mice, fcHFHS diet changed day-night eating patterns and PER2 clock-protein expression in the Lateral Habenula (LHb), a food-reward related area. In rats, no feeding patterns or clock-gene changes in LHb were found, however, Per2 gene expression was disrupted in the Nucleus Accumbens, which is indirectly connected to LHb. When blocking pharmacologically the glutamatergic functioning of the LHb, food intake was altered in both chow and fcHFHS-fed rats in a time-dependent manner. Finally, we tested the influence of Npas2 clock-gene on the disruption of rhythmic behavior produced by the fcHFHS-diet using Npas2 mutant and WT mice. Both genotypes, however, displayed similar altered eating patterns caused by the fcHFHS diet. Our findings indicate a relationship between nutrient type and an abnormal clock-gene expression in food reward-related areas, and an important role for the LHb in feeding behavior.
... Also, CO-HFD enhanced the hippocampal levels of NADPH oxidase, thus suggesting that activation of this enzyme is a major ROS-generating pathway in rats' hippocampi after chronic consumption of CO-HFD. Supporting these data, several authors have also shown that CO-HFD is associated with such metabolic phenotype and IR [40,50,51]. Besides, short or long term exposure to HFD impaired both short and long term hippocampal-dependent learning and memory in adult, juvenile and aged rats or mice [5,6,52,53]. ...
This study investigated the effect of a high-fat diet rich in corn oil (CO-HFD) on the memory retention and hippocampal oxidative stress, inflammation, and apoptosis in rats, and examined if the underlying mechanisms involve modulating Resolvin D1 (RvD1) levels and activation of p66Shc. Also, we tested if co-administration of RvD1 could prevent these neural adverse effects induced by CO-HFD. Adult male Wistar rats were divided into 4 groups (n = 18/each) as control fed standard diet (STD) (3.82 kcal/g), STD + RvD1 (0.2 µg/Kg, i.p/twice/week), CO-HFD (5.4 kcal/g), and CO-HFD + RvD1. All treatments were conducted for 8 weeks. With normal fasting glucose levels, CO-HFD induced hyperlipidemia, hyperinsulinemia, increased HOMA-IRI and reduced the rats’ memory retention. In parallel, CO-HFD increased levels of reactive oxygen species (ROS), malondialdehyde (MDA), cytoplasmic cytochrome-c, and cleaved caspase-3 and significantly decreased levels of glutathione (GSH), Bcl-2, and manganese superoxide dismutase (MnSOD) in rats’ hippocampi. Besides, CO-HFD significantly reduced hippocampal levels of docosahexaenoic acid (DHA) and RvD1, as well as total protein levels of Nrf2 and significantly increased nuclear protein levels of p-NF-κB. Concomitantly, CO-HFD increased hippocampal protein levels of p-JNK, p53, p66Shc, p-p66Shc, and NADPH oxidase. However, without altering plasma and serum levels of glucose, insulin, and lipids, co-administration of RvD1 to CO-HFD completely reversed all these events. It also resulted in similar effects in the STD fed-rats. In conclusion, CO-HFD impairs memory function and induces hippocampal damage by reducing levels of RvD1 and activation of JNK/p53/p66Shc/NADPH oxidase, effects that are prevented by co-administration of RvD1.
... Indeed, T2DM patient does not develop hyperglycemia due to the compensatory effect of β-cells [40]. In support, [41] have recently shown that CO-HFD reduces spontaneous locomotor activity and induces insulin resistance in mice. Also, n-6 PUFAs increased the secretion of insulin and/or reduces peripheral insulin catabolism and action in rodents [42][43][44]. ...
... In addition, the olfactory cues and the oily texture of corn oil are important orosensory factors provoking a strong appetite in mice [57]. However, other reports showed that the excess dietary intake of polyunsaturated fatty acids is associated with loss of spontaneous physical activity and development of insulin resistance [58]. In addition, polyunsaturated fatty acids are subject to oxidation. ...
The laboratory mouse is the most common used mammalian research model in biomedical research. Usually these animals are maintained in germ-free, gnotobiotic, or specific-pathogen-free facilities. In these facilities, skilled staff takes care of the animals and scientists usually don’t pay much attention about the formulation and quality of diets the animals receive during normal breeding and keeping. However, mice have specific nutritional requirements that must be met to guarantee their potential to grow, reproduce and to respond to pathogens or diverse environmental stress situations evoked by handling and experimental interventions. Nowadays, mouse diets for research purposes are commercially manufactured in an industrial process, in which the safety of food products is addressed through the analysis and control of all biological and chemical materials used for the different diet formulations. Similar to human food, mouse diets must be prepared under good sanitary conditions and truthfully labeled to provide information of all ingredients. This is mandatory to guarantee reproducibility of animal studies. In this review, we summarize some information on mice research diets and general aspects of mouse nutrition including nutrient requirements of mice, leading manufacturers of diets, origin of nutrient compounds, and processing of feedstuffs for mice including dietary coloring, autoclaving and irradiation. Furthermore, we provide some critical views on the potential pitfalls that might result from faulty comparisons of grain-based diets with purified diets in the research data production resulting from confounding nutritional factors.
... Indeed, T2DM patient does not develop hyperglycemia due to the compensatory effect of β-cells [40]. In support, [41] have recently shown that CO-HFD reduces spontaneous locomotor activity and induces insulin resistance in mice. Also, n-6 PUFAs increased the secretion of insulin and/or reduces peripheral insulin catabolism and action in rodents [42][43][44]. ...
This study investigated if calcineurin/nuclear factor of activated T cells (NFAT) axis mediates the cardiac apoptosis in rats with type 1 diabetes mellitus (T1DM)-induced rats or administered chronically high-fat diet rich in corn oil (CO-HFD). Also, it investigated the impact of chronic administration of CO-HFD on Fas/Fas ligand (Fas/FasL)-induced apoptosis in the hearts of T1DM-induced rats. Adult male Wistar rats (140-160 g) were classified as control: (10% fat) CO-HFD: (40% fat), T1DM, and T1DM + CO-HFD (n=20/each). In vitro, cardiomyocytes were cultured in either low glucose (LG) or high glucose (HG) media in the presence or absence of linoleic acid (LA) and other inhibitors. Compared to the control, increased reactive oxygen species (ROS), protein levels of cytochrome C, cleaved caspase-8 and caspase-3, myocardial damage and impeded left ventricular (LV) function were observed in the hearts of all treated groups and maximally in T1DM + CO-HFD-treated rats. mRNA of all NFAT members (NFAT1-4) were not affected by any treatment. CO-HFD or LA significantly up-regulated Fas levels in both LVs and cultured cardiomyocytes in a ROS dependent mechanism and independent of modulating intracellular Ca2+ levels or calcineurin activity. T1DM or hyperglycemia significant up-regulated mRNA and protein levels of Fas and FasL by activating Ca2+/calcineurin/NFAT-4 axis. Furthermore, Fas/FasL cell death induced by recombinant FasL (rFasL) or HG media was enhanced by pre-incubating the cells with LA. In conclusion, activation of the Ca2+/calcineurin/NFAT4 axis is indispensable for hyperglycemia-induced Fas/FasL cell death in the cardiomyocytes and CO-HFD sensitizes this by up-regulation of Fas.
... This procedure was done on 12 rats/group. OGTT was performed one day post the last treatment and IPITT was performed two day later on 12-h fasted rats according to Wong et al. (2015). Plasma glucose was measured using a colorimetric kit (Cat. ...
This study investigated the effects corn oil (CO) and different ratios of corn oil plus fish oil (FO) on insulin signaling in rat's heart. Adult male rats were fed low (LFD) or isocaloric high-fat diets (HFDs) of CO alone or CO + FO (ratios of 9:1 or 4:1). Cultured cardiomyocytes were treated with linoleic acid (LA), DHA + EPA (1:1) or LA + (DHA + EPA) (1:1). CO induced peripheral and cardiac insulin resistance with mitochondria damage, lipotoxicity activation of PKCε. It also upregulated LV levels of PPARα and down regulated PPARβ/δ. FO antagonized corn oil effects at both ratio with more profound effects with the ratio of 4:1. The regulatory roles of CO and FO on PPARs was shown in cultured cardiomyocytes and independent of hyperinsulinemia or free fatty acids. In conclusion, reducing the ratio of n-6/n-3 PUFAs in our diet toward a value of one is cardioprotective.
... On the other hand, the continuous access to fat did not induce locomotor changes, which is in line with other studies that did not report changes in the Open Field test after 8 weeks of high fat diet treatment in adolescent mice [16]. Our results could be due to an adolescence-based effect, as other studies with adult mice have reported a decrease in motor activity [55,56]. Previous studies have shown that the animal's age plays an important role in locomotor activity. ...
Over the past few years, the effects of a high-fat diet (HFD) on cognitive functions have been broadly studied as a model of obesity, although no studies have evaluated whether these effects are maintained after the cessation of this diet. In addition, the behavioral effects of having a limited access to an HFD (binge-eating pattern) are mostly unknown, although they dramatically increase the vulnerability to drug use in contrast to having continuous access. Thus, the aim of the present study was to compare the effects of an intermittent versus a continuous exposure to an HFD during adolescence on cognition and anxiety-like behaviors, as well as to study the changes observed after the interruption of this diet. Adolescent male mice received for 40 days a standard diet, an HFD with continuous access or an HFD with sporadic limited access (2 h, three days a week). Two additional groups were fed with intermittent or continuous access to the HFD and withdrawn from this diet 15 days before the behavioral tests. Only the animals with a continuous access to the HFD showed higher circulating leptin levels, increased bodyweight, marked memory and spatial learning deficits, symptoms that disappeared after 15 days of HFD abstinence. Mice that binged on fat only showed hyperlocomotion, which normalized after 15 days of HFD cessation. However, discontinuation of fat, either in a binge or a continuous pattern, led to an increase in anxiety-like behavior. These results highlight that exposure to a high-fat diet during adolescence induces alterations in brain functions, although the way in which this diet is ingested determines the extent of these behavioral changes.
... Furthermore, decreased peristalsis (contractility of muscle), and increased oxidative stress response predicted in the corn oil group may be in response to increased microbial invaders. This supports the phenotype observed in previous studies using a similar diet which showed n-6 PUFA results in increased oxidative stress and tissue damage [11,52], increased inflammation and mortality during enteric infection [9,11], and metabolic insufficiencies [53]. Our data, in combination with previous literature, indicates that increased n-6 PUFA in the diet may be a risk factor for the development of a dysfunctional barrier in the gut. ...
The dynamics of the tripartite relationship between the host, gut bacteria and diet in the gut is relatively unknown. An imbalance between harmful and protective gut bacteria, termed dysbiosis, has been linked to many diseases and has most often been attributed to high-fat dietary intake. However, we recently clarified that the type of fat, not calories, were important in the development of murine colitis. To further understand the host-microbe dynamic in response to dietary lipids, we fed mice isocaloric high-fat diets containing either milk fat, corn oil or olive oil and performed 16S rRNA gene sequencing of the colon microbiome and mass spectrometry-based relative quantification of the colonic metaproteome. The corn oil diet, rich in omega-6 polyunsaturated fatty acids, increased the potential for pathobiont survival and invasion in an inflamed, oxidized and damaged gut while saturated fatty acids promoted compensatory inflammatory responses involved in tissue healing. We conclude that various lipids uniquely alter the host-microbe interaction in the gut. While high-fat consumption has a distinct impact on the gut microbiota, the type of fatty acids alters the relative microbial abundances and predicted functions. These results support that the type of fat are key to understanding the biological effects of high-fat diets on gut health.
... An alteration in the ratio of these phyla in response to diet or age is also known to occur in inflammatory bowel disease, aging, diabetes, and the metabolic syndrome (14). High levels of n-6 with low levels of-n-3 fatty acids in the diet has been linked to several other proinflammatory conditions such as insulin resistance, atherosclerosis, diabetes, and myocardial infarction (MI) (15)(16)(17)(18)(19). Disruption of immune-responsive bacterial populations due to aging and diet alteration on the immunologic scale is incomplete. ...
Calorie-dense obesogenic diet (OBD) is a prime risk factor for cardiovascular disease in aging. However, increasing age coupled with changes in the diet can affect the interaction of intestinal microbiota influencing the immune system, which can lead to chronic inflammation. How age and calorie-enriched OBD interact with microbial flora and impact leukocyte profiling is currently under investigated. Here, we tested the interorgan hypothesis to determine whether OBD in young and aging mice alters the gut microbe composition and the splenic leukocyte profile in acute heart failure (HF). Young (2-mo-old) and aging (18-mo-old) mice were supplemented with standard diet (STD, ∼4% safflower oil diet) and OBD (10% safflower oil) for 2 mo and then subjected to coronary artery ligation to induce myocardial infarction. Fecal samples were collected pre- and post-diet intervention, and the microbial flora were analyzed using 16S variable region 4 rRNA gene DNA sequencing and Quantitative Insights Into Microbial Ecology informatics. The STD and OBD in aging mice resulted in an expansion of the genus Allobaculum in the fecal microbiota. However, we found a pathologic change in the neutrophil:lymphocyte ratio in aging mice in comparison with their young counterparts. Thus, calorie-enriched OBD dysregulated splenic leukocytes by decreasing immune-responsive F4/80+ and CD169+ macrophages in aging mice. OBD programmed neutrophil swarming with an increase in isoprostanoid levels, with dysregulation of lipoxygenases, cytokines, and metabolite-sensing receptor expression. In summary, calorie-dense OBD in aging mice disrupted the composition of the gut microbiome, which correlates with the development of integrative and system-wide nonresolving inflammation in acute HF.-Kain, V., Van Der Pol, W., Mariappan, N., Ahmad, A., Eipers, P., Gibson, D. L., Gladine, C., Vigor, C., Durand, T., Morrow, C., Halade, G. V. Obesogenic diet in aging mice disrupts gut microbe composition and alters neutrophil:lymphocyte ratio, leading to inflamed milieu in acute heart failure.
... In this study, ingestion of HFD was associated with decrease in locomotor activity, rearing, grooming, and spatial working memory; while increase in anxiety-related behaviours, lipid peroxidation levels and acetylcholinesterase activity were also observed. These results corroborate those of previous studies [60][61][62][63][64]. The behavioural effects of HFD have been linked to its ability to alter the function of circadian clock genes and the circadian system [65], as well as alter the expression of nuclear factor kappa beta gene and the function of the hippocampal stress-related glucocorticoid and mineralocorticoid receptor genes [62]. ...
Effects of food-added monosodium glutamate (MSG) on neurobehaviour, serum biochemical parameters, malondialdehyde (MDA) levels, and changes in cerebral cortex, liver and kidney morphology were assessed in mice fed standard diet (SD) or high-fat diet (HFD). Animals were assigned to 8 groups [SD control, HFD control, and six groups fed MSG plus SD or HFD at 0.1, 0.2 and 0.4 g/kg of feed]. Animals were fed for 8 weeks, behavioural tests were conducted, and blood was taken for estimation of biochemical parameters and MDA level. Whole brain was homogenised for neurochemical assays, while the cerebrum, liver and kidneys were processed for histology.
In groups fed MSG/SD, there was a decrease in weight gain, increase in food-intake, an increase in locomotion, a decrease in rearing/grooming, and a decrease in anxiety-response. Also observed were derangements in biochemical parameters, increased MDA, and alteration of renal morphology. Compared to HFD, MSG/HFD groups had reduction in weight gain, food-intake, grooming and anxiety-response, an increase in locomotion, and improved memory. Protection against biochemical derangements and HFD-induced organ injuries were also observed. In conclusion, the findings suggest that possible interactions that may occur between dietary constituents and MSG are determinants of the effects of food-added MSG in mice.
... In this study, ingestion of HFD was associated with decrease in locomotor activity, rearing, grooming, and spatial working memory; while increase in anxiety-related behaviours, lipid peroxidation levels and acetylcholinesterase activity were also observed. These results corroborate those of previous studies [60][61][62][63][64]. The behavioural effects of HFD have been linked to its ability to alter the function of circadian clock genes and the circadian system [65], as well as alter the expression of nuclear factor kappa beta gene and the function of the hippocampal stress-related glucocorticoid and mineralocorticoid receptor genes [62]. ...
Effects of food-added monosodium glutamate (MSG) on neurobehaviour, serum biochemical parameters, malondialdehyde (MDA) levels, and changes in cerebral cortex, liver and kidney morphology were assessed in mice fed standard diet (SD) or high-fat diet (HFD). Animals were assigned to 8 groups [SD control, HFD control, and six groups fed MSG plus SD or HFD at 0.1, 0.2 and 0.4 g/kg of feed]. Animals were fed for 8 weeks, behavioural tests were conducted, and blood was taken for estimation of biochemical parameters and MDA level. Whole brain was homogenised for neurochemical assays, while the cerebrum, liver and kidneys were processed for histology.
In groups fed MSG/SD, there was a decrease in weight gain, increase in food-intake, an increase in locomotion, a decrease in rearing/grooming, and a decrease in anxiety-response. Also observed were derangements in biochemical parameters, increased MDA, and alteration of renal morphology. Compared to HFD, MSG/HFD groups had reduction in weight gain, food-intake, grooming and anxiety-response, an increase in locomotion, and improved memory. Protection against biochemical derangements and HFD-induced organ injuries were also observed. In conclusion, the findings suggest that possible interactions that may occur between dietary constituents and MSG are determinants of the effects of food-added MSG in mice.
... It should be noted that there was no difference in the time of exploration between CD and HFD on phase 1 (sample phase) and both CD and HFD preferred to explore the juvenile animal compared with the object. This suggests that the differences at the test phase could not be attributed to differences in locomotion activity, consistent with findings with longer periods of HFD (Wong et al. 2015;Chia-Ying et al. 2017). Together, suggesting that the effects of HFD on memory are not related to motor changes or attentional factors per se. ...
Juvenility represents a critical developmental phase during which exposure to a high fat diet (HFD) can severely modify cognitive and emotional functioning. The purpose of this study was to address how short and acute exposure to a HFDduring juvenility affects social memory recognition and prefrontal long-term potentiation (LTP). As LTP and social memory depend on the neuromodulator oxytocin (OXY) and due to its role in metabolism, we also examined the effects of OXY inmediating HFD-induced alterations in social memory and LTP. Our results show that short exposure to a HFD duringjuvenility impairs social preference memory and prefrontal LTP. Interestingly, whereas systemic injections of OXY reversedthe impairments in HFD-fed animals and impaired LTP and memory in control animals; prefrontal injections of the OXY agonist TGOT reversed the effects in HFD animals without affecting control animals. Exposure to HFD was associated with areduction in the levels of OXY in the prefrontal compared to control animals. Interestingly, the restoration of social memory by TGOT in HFD animals was also associated with normalization of OXY in the prefrontal. These results point to a role that prefrontal OXY has in mediating the effects of HFD on memory and plasticity
... Heparinized blood was centrifuged at 2,000g for 15 min at 4°C to separate plasma. Body composition analysis and metabolic cage experiments were performed as previously described (11). ...
p300 (EP300) and CBP (CREBBP) are transcriptional coactivators with histone acetyltransferase activity. Various beta cell transcription factors can recruit p300/CBP, and thus the coactivators could be important for beta cell function and health in vivo We hypothesized that p300/CBP contribute to the development and proper function of pancreatic islets. To test this, we bred and studied mice lacking p300/CBP in their islets. Mice lacking either p300 or CBP in islets developed glucose intolerance attributable to impaired insulin secretion, together with reduced alpha and beta cell area and islet insulin content. These phenotypes were exacerbated in mice with only a single copy of p300 or CBP expressed in islets. Removing p300 in pancreatic endocrine progenitors impaired proliferation of neonatal alpha and beta cells. Mice lacking all four copies of p300/CBP in pancreatic endocrine progenitors failed to establish alpha and beta cell mass postnatally. Transcriptomic analyses revealed significant overlaps between p300/CBP-downregulated genes and genes downregulated in Hnf1α-null islets and Nkx2.2-null islets, among others. Furthermore, p300/CBP are important for the acetylation of H3K27 at loci downregulated in Hnf1α-null islets. We conclude that p300 and CBP are limiting cofactors for islet development, and hence for postnatal glucose homeostasis, with some functional redundancy.
... Various high fat diets with diff erent sources of fat (saturated, and unsaturated) and diff erent proportions of fat of the total energy expenditure are widely used in animals studies to induce obesity [10][11][12][13], which is also widely used to examine obesity-induced chronic state of low-grade infl ammation, mediated through quantitative and phenotype switching in white adipose tissue macrophages (ATM) [14]. Th erefore, the objective of this study was to examine iron homeostasis and tissue iron quantifi cation in female rats aft er feeding diff erent High-Fat-Diets (HFDs) for six and ten weeks. ...
Background: Obesity has been associated with anemia of chronic disease and it may also promote iron defi ciency causing dysmetabolic iron overload. Objective: The aim of this study was to examine iron homeostasis on serum and tissue after feeding rats with various high-fat-diets for 6 and 10 weeks. Methods: Eight weeks Sprague - Dawley female rats were randomly divided into three main dietary groups: Group (1): rats were fed the High Saturated Fat Diet Group (HSFD; n = 12), group (2): rats were fed the High Monounsaturated Fat Diet Group (HMUSFD; n = 12) and group (3): rats were fed Normal Fat Diet Group (NFD) (n = 12) for 6 and 10 weeks. Blood samples were collected; liver and Retroperitoneal Adipose Tissues (RPAT) was removed. Serum iron parameters and the total iron quantifi cation in tissue were measured. Results: Findings after 6 weeks demonstrated that no signifi cant elevation in all tested iron parameters in serum and tissue in HFDs fed groups as compared to NFD controls. On the other hand, feeding rats with different HFDs for 10 weeks leading to increase serum ferritin signifi cantly as compared to NFD, and liver iron content was increased signifi cantly in rats that were fed HSFD and NFD (178.16 ± 7.78, 168.67 ± 5.42 ng/ mg, respectively) as compared to HMUFD (123.78 ± 6.57ng/ mg)(p ˂ 0.05). Conclusion: The effect of the high-fat-diets on iron homeostasis is time dependent. However, the type of dietary fat that introduce will affect tissue iron deposition. Keywords: High-fat-diets; Iron homeostasis; Tissue iron deposition
... Within the brain, NPY, 5-HT and DA are rhythmic-expressing molecules that are also affected in the obese state (Pritchet and Hajnal, 2011;Koopman et al., 2013;Gumbs et al., 2015). At the level of the clock gene expression, the hyper caloric diet largely alters clock gene expression in peripheral organs such as the liver and adipose tissue with varying effects depending on the energy content of the diet, the age and species of the animals used in the studies as well as the duration of the diet (Pendergast et al., 2013;Branecky et al., 2015;Wong et al., 2015;Cunningham et al., 2016). With regard to rhythmic expression of neuropeptides and clock-genes in the brain only few studies have focused on the effects of a diet-induced obesity (DIO). ...
Feeding behavior shows a rhythmic daily pattern, which in nocturnal rodents is observed mainly during the dark period. This rhythmicity is under the influence of the hypothalamic suprachiasmatic nucleus (SCN), the main biological clock. Nevertheless, various studies have shown that in rodent models of obesity, using high-energy diets, the general locomotor activity and feeding rhythms can be disrupted. Here, we review the data on the effects of diet-induced obesity (DIO) on locomotor activity and feeding patterns, as well as the effect on the brain sites within the neural circuitry involved in metabolic and rewarding feeding behavior. In general, DIO may alter locomotor activity by decreasing total activity. On the other hand, DIO largely alters eating patterns, producing increased overall ingestion and number of eating bouts that can extend to the resting period. Furthermore, within the hypothalamic areas, little effect has been reported on the molecular circadian mechanism in DIO animals with ad libitum hypercaloric diets and little or no data exist so far on its effects on the reward system areas. We further discuss the possibility of an uncoupling of metabolic and reward systems in DIO and highlight a gap of circadian and metabolic research that may help to better understand the implications of obesity.
... Even more surprising was that HFD so rapidly decreased spontaneous activity in both WT and foz/foz mice, well before the onset of obesity. The literature provides little and conflicting data pertaining to this: some reports suggest that the relative increase in saturated fat compared with unsaturated fat matters [23][24][25] whereas other suggest a contribution of HFD-induced insulin resistance [23] or secondary obesity. In the model we used, we propose that the addition of high saturated lipid intake and decreased muscle energy expenditure results in to rapid obesity and insulin resistance if not compensated for by brown adipose energy combustion. ...
Fatty liver diseases are complications of the metabolic syndrome associated with obesity, insulin resistance and low grade inflammation. Our aim was to uncover mechanisms contributing to hepatic complications in this setting. We used foz/foz mice prone to obesity, insulin resistance and progressive fibrosing NASH. Foz/foz mice are hyperphagic but WT-matched calorie intake failed to protect against obesity, adipose inflammation and glucose intolerance. Obese foz/foz mice had similar physical activity level but reduced energy expenditure. Thermogenic adaptation to high-fat diet or to a cold exposure was severely impaired in foz/foz mice compared to HFD-fed WT littermates due to lower sympathetic tone in their brown adipose tissue (BAT). Intermittent cold exposure restored BAT function and thereby improved glucose tolerance, decreased fat mass and liver steatosis. We conclude that failure of BAT adaptation drives the metabolic complications of obesity in foz/foz mice, including development of liver steatosis. Induction of endogenous BAT function had a significant therapeutic impact on obesity, glucose tolerance and liver complications and is a potential new avenue for therapy of non-alcoholic fatty liver disease.
... In a third study, Dr. Ghosh's research group examined the role of n-6 PUFA consumption in physical inactivity and insulin resistance in female mice (22). They found that compared to mice fed OO or chow diets, CO-fed mice experienced reduced spontaneous locomotor activity after 6 weeks on the diet. ...
... Blunt arrows show factors which can decrease arachidonic acid stimulated adipogenesis. muscle (therefore reducing its ability to oxidise FA) in comparison to high oleic acid (OA) (from olive oil) fed animals [78]. ...
... It has been shown that ghrelin has differential effects on dopaminergic activity in midbrain SN and VTA (35,45,46). In agreement with the literature (47,48), our data show that HFD reduces physical activity and promotes DIO. Higher expression of TH and DAT was detected in SN of HFD-fed Syn1-Cre;Ghsr f/f mice, which suggests that dopamine turnover and activity might be elevated in the SN; that is in agreement with the increased physical activity observed in HFD-fed Syn1-Cre;Ghsr f/f mice. ...
Ghrelin signaling has major effects on energy- and glucose-homeostasis, but it is unknown whether ghrelin's functions are centrally and/or peripherally mediated. The ghrelin receptor, Growth Hormone Secretagogue Receptor (GHS-R), is highly expressed in brain and detectable in some peripheral tissues. To understand the roles of neuronal GHS-R, we generated a mouse line where Ghsr gene is deleted in all neurons using Synapsin 1-Cre driver. Our data showed that neuronal Ghsr deletion abolishes ghrelin-induced spontaneous food intake, but has no effect on total energy intake. Remarkably, neuronal Ghsr deletion almost completely prevented diet-induced obesity (DIO) and significantly improved insulin sensitivity. The neuronal Ghsr deleted mice also showed improved metabolic flexibility, indicative of better adaption to different fuels. In addition, gene expression analysis suggested that hypothalamus and/or midbrain might be the sites that mediate the effects of GHS-R in thermogenesis and physical activity, respectively. Collectively, our results indicate that neuronal GHS-R is a crucial regulator of energy metabolism and a key mediator of DIO. Neuronal Ghsr deletion protects against DIO by regulating energy expenditure, not by energy intake. These novel findings suggest that suppressing central ghrelin signaling may serve as a unique anti-obesity strategy.
... Within this context, it is important to note that Nrg1 mice appeared protected against the locomotor-suppressive effects of HFD. This protective effect of the Nrg1 mutation on HFD-induced hypolocomotion requires further investigations as earlier work has reported diet-induced suppression of locomotion in female C57BL/6J mice, which was dependent on the type of HFD (Wong et al. 2015) and potentially due to a diet-induced shift in the circadian rhythm of mice (Kohsaka et al. 2007). ...
Schizophrenia patients are often obese or overweight and poor dietary choices appear to be a factor in this phenomenon. Poor diet has been found to have complex consequences for the mental state of patients. Thus, this study investigated whether an unhealthy diet (i.e. high fat diet: HFD) impacts on the behaviour of a genetic mouse model for the schizophrenia risk gene neuregulin 1 (i.e. transmembrane domain Nrg1 mutant mice: Nrg1 HET). Female Nrg1 HET and wild type-like littermates (WT) were fed with either HFD or a control chow diet. The mice were tested for baseline (e.g. anxiety) and schizophrenia-relevant behaviours after 7 weeks of diet exposure. HFD increased body weight and impaired glucose tolerance in all mice. Only Nrg1 females on HFD displayed a hyper-locomotive phenotype as locomotion-suppressive effects of HFD were only evident in WT mice. HFD also induced an anxiety-like response and increased freezing in the context and the cued version of the fear conditioning task. Importantly, CHOW-fed Nrg1 females displayed impaired social recognition memory, which was absent in HFD-fed mutants. Sensorimotor gating deficits of Nrg1 females were not affected by diet. In summary, HFD had complex effects on the behavioural phenotype of test mice and attenuated particular cognitive deficits of Nrg1 mutant females. This topic requires further investigations thereby also considering other dietary factors of relevance for schizophrenia as well as interactive effects of diet with medication and sex.
The Mediterranean diet (MD) is a health-promoting diet containing approximately 40% total fat. It is not known if the blend of fats found in the MD contribute to the beneficial protective effects. We compared the MD fat blend (high monounsaturated, 2:1 n-6:n-3 polyunsaturated and moderate saturated fat) to isocaloric diets composed with corn oil (CO, n-6 polyunsaturated-rich), olive oil (high monounsaturated-rich) or milk fat (MF, saturated-rich) on spontaneous colitis development in Muc2-/- mice. The MD resulted in lower clinical and histopathological scores, and induced tolerogenic CD103+CD11b+ dendritic, Th22 and IL-17+IL-22+ cells important for intestinal barrier repair. MD also reduced attendant insulin resistance and a shift to a higher health-promoting gut microbes including Lactobacillus animalis and Muribaculaceae, whereas CO showed higher prevalence of mucin-degraders (Akkermansia muciniphila) and colitis promoters (Enterobacteriaceae). Our findings suggest that the MD fat blend could be recommended as a maintenance diet for colitis.
This study investigated the effect of chronic consumption of a high‐fat diet rich in corn oil (CO‐HFD) on atrial cells ultrastructure, antioxidant levels and markers of intrinsic cell death of both control and type 1 diabetes mellitus (T1DM)‐induced rats. Adult male rats (10 rats/each) were divided into 4 groups: control fed standard diet (STD) (3.82 Kcal/g, 9.4% fat), CO‐HFD (5.4 Kcal/g, 40% fat), T1DM fed STD, and T1DM + CO‐HFD. CO‐HFD and T1DM alone or in combination impaired systolic and diastolic functions of rats and significantly reduced levels of GSH and the activity of SOD, enhanced lipid peroxidation, increased protein levels of P53, Bax, cleaved caspase‐3, and ANF and decreased levels of Bcl‐2 in their atria. Concomitantly, atrial cells exhibited fragmentation of the myofibrils, disorganized mitochondria, decreased number of atrionatriuretic factor (ANF) granules, and loss of gap junctions accompanied by changes in capillaries walls. Among all treatments, the severity of all these findings was more severe in T1DM and most profound in the atria of T1DM + CO‐HFD. In conclusion, chronic consumption of CO‐HFD by T1DM‐induced rats elicits significant biochemical and ultrastructural damage to rat atrial cells accompanied by elevated oxidative stress and mitochondria‐mediated cell death. This article is protected by copyright. All rights reserved.
Scope
To assess the associations of dietary linoleic acid (LA) and α‐linolenic acid (ALA) with type 2 diabetes (T2D) risk in a population‐based cohort and further explore the mechanism of action in a high‐fat‐diet induced obese (DIO) mouse model.
Methods and results
The occurrence of T2D among 15,100 healthy Chinese adults from China Health and Nutrition Survey (CHNS, 1997–2011) were followed up for a median of 14 years. The relations of ALA and LA intakes with T2D risk were modified by BMI, with significant associations restricted to obese/overweight subjects. Among them, relative risks (95% confidence intervals) comparing extreme quartiles of intakes were 0.55 (0.32‐0.93) in men and 0.53 (0.34‐0.85) in women for ALA, while 0.71 (0.41‐1.16) in men and 0.56 (0.36‐0.89) in women for LA. DIO mice were fed with LA or ALA enriched HFD (0.2% wt/wt) for 15 weeks. Significant sex‐dependent changes of gut microbiota were detected in LA or ALA fed DIO mice. Endotoxemia, systematic and adipose inflammation were relieved in ALA fed male mice and LA fed female mice.
Conclusions
Long‐term intake of LA (for women only) and ALA may have protective effect on T2D development for obese/overweight subjects through sex‐specific gut microbiota modulation and gut‐adipose axis.
This article is protected by copyright. All rights reserved
Overweight and obesity result from an imbalance between caloric intake and energy expenditure, including expenditure from spontaneous physical activity (SPA). Changes in SPA and resulting changes in non-exercise activity thermogenesis (NEAT) likely interact with diet to influence risk for obesity. However, previous research on the relationship between diet, physical activity, and energy expenditure has been mixed. The neuropeptide orexin is a driver of SPA, and orexin neuron activity can be manipulated using DREADDs (Designer Receptors Exclusively Activated by Designer Drugs). We hypothesized that HFD decreases SPA and NEAT, and that DREADD-mediated activation of orexin neuron signaling would abolish this decrease and produce an increase in NEAT instead. To test these ideas, we characterized behaviors to determine the extent to which access to a high-fat diet (HFD) influences the proportion and probability of engaging in food intake and activity. We then measured NEAT following access to HFD and following a DREADD intervention targeting orexin neurons. Two cohorts of orexin-cre male mice were injected with an excitatory DREADD virus into the caudal hypothalamus, where orexin neurons are concentrated. Mice were then housed in continuous metabolic phenotyping cages (Sable Promethion). Food intake, indirect calorimetry, and SPA were automatically measured every second. For cohort 1 (n=8), animals were given access to chow, then switched to HFD. For cohort 2 (n=4/group), half of the animals were given access to HFD, the other access to chow. Then, among animals on HFD, orexin neurons were activated following injections of clozapine n-oxide (CNO). Mice on HFD spent significantly less time eating (p<0.01) and more time inactive compared to mice on chow (p<0.01). Following a meal, mice on HFD were significantly more likely to engage in periods of inactivity compared to those on chow (p<0.05). NEAT was decreased in animals on HFD, and was increased to the NEAT level of control animals following activation of orexin neurons with DREADDs. Food intake (kilocalories) was not significantly different between mice on chow and HFD, yet mice on chow expended more energy per unit of SPA, relative to that in mice consuming HFD. These results suggest that HFD consumption reduces SPA and NEAT, and increases inactivity following a meal. Together, the data suggest a change in the efficiency of energy expenditure based upon diet, such that SPA during HFD burns fewer calories compared to SPA on a standard chow diet.
Anecdotal evidence suggests that the incorporation of n-6 polyunsaturated fatty acid (n-6 PUFA) containing oilseeds in dairy feeds deplete saturated fatty acids (SFA) in dairy fats like butter. However, due to the lack of chemical evidence, the current status of n-6 PUFA or SFA in butter is unknown. We hypothesized that n-6 PUFA levels in commercial butter were inversely proportional to its SFA content and directly proportional to the extent of n-6 PUFA-rich oilseed production of its country of origin. We analyzed grass-fed and commercial butters from Australia, Belarus, Canada, China, England, France, Germany, Iceland, India, Israel, Japan, Netherlands, New Zealand, Russia and the USA via gas chromatography. Extent of n-6 PUFA containing oilseed production for countries was obtained from the FAOStat 2015 database. Globally, SFA from commercial butters had a strong negative correlation (Spearman r = -0.53, p=0.025) with its n-6 PUFA content, with USA and Canadian butter demonstrating the highest n-6 PUFA as well as n-6/n-3 PUFA ratios. As predicted, we show that countries with more than 5% of its agricultural land dedicated to n-6 PUFA oilseed production, demonstrate a 'spillover' increase of n-6 PUFA in their commercial butters (Spearman r =0.85, p=0.0054). The overall significance of this study is that it presents novel evidence of the global impact of rising n-6 PUFA production on commercial butter fat composition. We hope this data will lead to inclusion of actual biochemical analyses of dairy fats in future clinical trials. We believe that this inclusion of analyses will better explain the differential health outcomes among different countries for such interventions.
Purpose:
Compare equal energy deficits induced by exercise and caloric reduction on cardiometabolic disease risk parameters including AT inflammation, IR and gut microbiota changes during HFD consumption.
Methods:
Obesity-prone rats fed HFD were exercise trained (Ex, n=10) or weight-matched to Ex via caloric reduction while kept sedentary (WM, n=10), and compared to ad libitum HFD-fed (Sed, n=10) rats for IR, systemic energetics and spontaneous physical activity (SPA), adiposity, and fasting metabolic parameters. Visceral, subcutaneous, periaortic, and brown AT, liver, aorta, and cecal digesta were examined.
Results:
Despite identical reductions in adiposity, Ex, but not WM, improved IR, increased SPA by ~26% (p<0.05 compared to WM and Sed), and reduced LDL cholesterol (p<0.05 compared to Sed). WM and Ex both reduced inflammatory markers in all AT depots and aorta, while only Ex increased indicators of mitochondrial function in brown AT. Ex significantly increased the relative abundance of cecal Streptococcaceae and decreased S24-7 and one undefined genus in Rikenellacea; WM induced similar changes that did not reach statistical significance.
Conclusions:
Both Ex and WM reduced AT inflammation across depots, while Ex caused more robust changes to gut microbial communities, improved IR, increased fat oxidation, increased SPA, and increased indices of brown AT mitochondrial function. Our findings add to the growing body of literature indicating that there are weight-loss independent metabolic benefits of exercise.
A high-fat diet and elevated levels of free fatty acids are known risk factors for metabolic syndrome, insulin resistance, and visceral obesity. Although these disease associations are well established, it is unclear how different dietary fats change the risk of insulin resistance and metabolic syndrome. Here, we review emerging evidence that insulin resistance and fat storage are linked to changes in the gut microbiota. The gut microbiota and intestinal barrier function, in turn, are highly influenced by the composition of fat in the diet. We review findings that certain fats (for example, long-chain saturated fatty acids) are associated with dysbiosis, impairment of intestinal barrier function, and metabolic endotoxemia. In contrast, other fatty acids, including short-chain and certain unsaturated fatty acids, protect against dysbiosis and impairment of barrier function caused by other dietary fats. These fats may promote insulin sensitivity by inhibiting metabolic endotoxemia and dysbiosis-driven inflammation. During dysbiosis, the modulation of metabolism by diet and microbiota may represent an adaptive process that compensates for the increased fuel demands of an activated immune system.
The extent to which women of reproductive age are able to convert the n-3 fatty acid alpha-linolenic acid (ALNA) to eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) was investigated in vivo by measuring the concentrations of labelled fatty acids in plasma for 21 d following the ingestion of [U-13C]ALNA (700 mg). [13C]ALNA excursion was greatest in cholesteryl ester (CE) (224 (sem 70) micromol/l over 21 d) compared with triacylglycerol (9-fold), non-esterified fatty acids (37-fold) and phosphatidylcholine (PC, 7-fold). EPA excursion was similar in both PC (42 (sem 8) micromol/l) and CE (42 (sem 9) micromol/l) over 21 d. In contrast both [13C]DPA and [13C]DHA were detected predominately in PC (18 (sem 4) and 27 (sem 7) micromol/l over 21 d, respectively). Estimated net fractional ALNA inter-conversion was EPA 21 %, DPA 6 % and DHA 9 %. Approximately 22 % of administered [13C]ALNA was recovered as 13CO2 on breath over the first 24 h of the study. These results suggest differential partitioning of ALNA, EPA and DHA between plasma lipid classes, which may facilitate targeting of individual n-3 fatty acids to specific tissues. Comparison with previous studies suggests that women may possess a greater capacity for ALNA conversion than men. Such metabolic capacity may be important for meeting the demands of the fetus and neonate for DHA during pregnancy and lactation. Differences in DHA status between women both in the non-pregnant state and in pregnancy may reflect variations in metabolic capacity for DHA synthesis.
Dopaminergic function is thought to be altered in major depression and, in animal studies, is reduced in omega-3 polyunsaturated fatty acid (PUFA) deficiency states. Therefore we studied PUFAs and resting prolactin, a marker for dopaminergic tone, and cerebrospinal fluid homovanillic acid (HVA), the chief dopamine metabolite. In medication-free adults (n = 23) with DSM-IV major depressive disorder (MDD), we measured plasma phospholipid levels of omega-3 PUFAs docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), the omega-6 PUFA arachidonic acid (AA), and plasma prolactin levels before and after administration of dl-fenfluramine (FEN). In a subset of patients (n = 14), cerebrospinal fluid levels of HVA and the serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA), were obtained through lumbar puncture. Baseline prolactin was negatively correlated with omega-3 PUFAs (logDHA, F 1,21 = 20.380, p < 0.001; logEPA, F 1,21 = 10.051, p = 0.005) and positively correlated with logAA:DHA (F 1,21 = 15.263, p = 0.001), a measure of omega-6/omega-3 balance. LogDHA was negatively correlated with CSF HVA (Spearman's ρ = -0.675, p = 0.008) but not 5-HIAA (Spearman's ρ = -0.143, p = 0.626) after controlling for sex and HVA - 5-HIAA correlation. PUFAs did not predict the magnitude of the FEN-stimulated change in prolactin, considered to be a serotonin effect. The robust relationship of omega-3 PUFAs with dopaminergic but not serotonergic indices suggests that omega-6:omega-3 balance may impact depression pathophysiology through effects on the dopaminergic system.
Aim:
To systematically review data from different countries on population intakes of total fat, saturated fatty acids (SFA) and polyunsaturated fatty acids (PUFA), and to compare these to recommendations from the Food and Agriculture Organization of the United Nations/the World Health Organization (FAO/WHO).
Methods:
Data from national dietary surveys or population studies published from 1995 were searched via MEDLINE, Web of Science and websites of national public health institutes.
Results:
Fatty acid intake data from 40 countries were included. Total fat intake ranged from 11.1 to 46.2 percent of energy intake (% E), SFA from 2.9 to 20.9% E and PUFA from 2.8 to 11.3% E. The mean intakes met the recommendation for total fat (20-35% E), SFA (<10% E) and PUFA (6-11% E) in 25, 11 and 20 countries, respectively. SFA intake correlated with total fat intake (r = 0.76, p < 0.01) but not with PUFA intake (r = 0.03, p = 0.84). Twenty-seven countries provided data on the distribution of fatty acids intake. In 18 of 27 countries, more than 50% of the population had SFA intakes >10% E and in 13 of 27 countries, the majority of the population had PUFA intakes <6% E.
Conclusions:
In many countries, the fatty acids intake of adults does not meet the levels that are recommended to prevent chronic diseases. The relation between SFA and PUFA intakes shows that lower intakes of SFA in the populations are not accompanied by higher intakes of PUFA, as is recommended for preventing coronary heart disease.
Dietary intake of linoleic acid (LNA, 18:2n-6) has increased dramatically during the 20th century and is associated with greater prevalence of obesity. The endocannabinoid system is involved in regulation of energy balance and a sustained hyperactivity of the endocannabinoid system may contribute to obesity. Arachidonic acid (ARA, 20:4n-6) is the precursor for 2-AG and anandamide (AEA), and we sought to determine if low fat diets (LFD) could be made obesogenic by increasing the endocannabinoid precursor pool of ARA, causing excessive endocannabinoid signaling leading to weight gain and a metabolic profile associated with obesity. Mice (C57BL/6j, 6 weeks of age) were fed 1 en% LNA and 8 en% LNA in low fat (12.5 en%) and medium fat diets (MFD, 35 en%) for 16 weeks. We found that increasing dietary LNA from 1 to 8 en% in LFD and MFD significantly increased ARA in phospholipids (ARA-PL), elevated 2-AG and AEA in liver, elevated plasma leptin, and resulted in larger adipocytes and more macrophage infiltration in adipose tissue. In LFD, dietary LNA of 8 en% increased feed efficiency and caused greater weight gain than in an isocaloric reduction to 1 en% LNA. Increasing dietary LNA from 1 to 8 en% elevates liver endocannabinoid levels and increases the risk of developing obesity. Thus a high dietary content of LNA (8 en%) increases the adipogenic properties of a low fat diet.
PGC-1α, a transcriptional coactivator, controls inflammation and mitochondrial gene expression in insulin-sensitive tissues following exercise intervention. However, attributing such effects to PGC-1α is counfounded by exercise-induced fluctuations in blood glucose, insulin or bodyweight in diabetic patients. The goal of this study was to investigate the role of PGC-1α on inflammation and mitochondrial protein expressions in aging db/db mice hearts, independent of changes in glycemic parameters. In 8-month-old db/db mice hearts with diabetes lasting over 22 weeks, short-term, moderate-intensity exercise upregulated PGC-1α without altering body weight or glycemic parameters. Nonetheless, such a regimen lowered both cardiac (macrophage infiltration, iNOS and TNFα) and systemic (circulating chemokines and cytokines) inflammation. Curiously, such an anti-inflammatory effect was also linked to attenuated expression of downstream transcription factors of PGC-1α such as NRF-1 and several respiratory genes. Such mismatch between PGC-1α and its downstream targets was associated with elevated mitochondrial membrane proteins like Tom70 but a concurrent reduction in oxidative phosphorylation protein expressions in exercised db/db hearts. As mitochondrial oxidative stress was predominant in these hearts, in support of our in vivo data, increasing concentrations of H2O2 dose-dependently increased PGC-1α expression while inhibiting expression of inflammatory genes and downstream transcription factors in H9c2 cardiomyocytes in vitro. We conclude that short-term exercise-induced oxidative stress may be key in attenuating cardiac inflammatory genes and impairing PGC-1α mediated gene transcription of downstream transcription factors in type 2 diabetic hearts at an advanced age.
Background:
A reduction in dietary saturated fat has generally been thought to improve cardiovascular health.
Objective:
The objective of this meta-analysis was to summarize the evidence related to the association of dietary saturated fat with risk of coronary heart disease (CHD), stroke, and cardiovascular disease (CVD; CHD inclusive of stroke) in prospective epidemiologic studies.
Design:
Twenty-one studies identified by searching MEDLINE and EMBASE databases and secondary referencing qualified for inclusion in this study. A random-effects model was used to derive composite relative risk estimates for CHD, stroke, and CVD.
Results:
During 5-23 y of follow-up of 347,747 subjects, 11,006 developed CHD or stroke. Intake of saturated fat was not associated with an increased risk of CHD, stroke, or CVD. The pooled relative risk estimates that compared extreme quantiles of saturated fat intake were 1.07 (95% CI: 0.96, 1.19; P = 0.22) for CHD, 0.81 (95% CI: 0.62, 1.05; P = 0.11) for stroke, and 1.00 (95% CI: 0.89, 1.11; P = 0.95) for CVD. Consideration of age, sex, and study quality did not change the results.
Conclusions:
A meta-analysis of prospective epidemiologic studies showed that there is no significant evidence for concluding that dietary saturated fat is associated with an increased risk of CHD or CVD. More data are needed to elucidate whether CVD risks are likely to be influenced by the specific nutrients used to replace saturated fat.
Peroxisome proliferator-activated receptor a (PPARa) plays a key role in the transcriptional control of genes encoding mitochondrial fatty acid b-oxidation (FAO) enzymes. In this study we sought to determine whether the recently identified PPAR gamma coactivator 1 (PGC-1) is capable of coactivating PPARa in the transcriptional control of genes encoding FAO enzymes. Mammalian cell cotransfection experiments demon- strated that PGC-1 enhanced PPARa-mediated transcriptional activation of reporter plasmids containing PPARa target elements. PGC-1 also enhanced the transactivation activity of a PPARa-Gal4 DNA binding domain fusion protein. Retroviral vector-mediated expression studies performed in 3T3-L1 cells demonstrated that PPARa and PGC-1 cooperatively induced the expression of PPARa target genes and increased cellular palmitate oxidation rates. Glutathione S-transferase "pulldown" studies revealed that in contrast to the previously reported ligand-independent interaction with PPARg, PGC-1 binds PPARa in a ligand-influenced manner. Protein-protein interaction studies and mammalian cell hybrid experiments demonstrated that the PGC-1-PPARa interaction involves an LXXLL domain in PGC-1 and the PPARa AF2 region, consistent with the observed ligand influence. Last, the PGC-1 transactivation domain was mapped to within the NH2-terminal 120 amino acids of the PGC-1 molecule, a region distinct from the PPARa interacting domains. These results identify PGC-1 as a coactivator of PPARa in the transcriptional control of mitochondrial FAO capacity, define separable PPARa interaction and transactivation domains within the PGC-1 molecule, and demonstrate that certain features of the PPARa-PGC-1 interaction are distinct from that of PPARg-PGC-1.
To evaluate the effectiveness of replacing dietary saturated fat with omega 6 linoleic acid, for the secondary prevention of coronary heart disease and death.
Evaluation of recovered data from the Sydney Diet Heart Study, a single blinded, parallel group, randomized controlled trial conducted in 1966-73; and an updated meta-analysis including these previously missing data.
Ambulatory, coronary care clinic in Sydney, Australia.
458 men aged 30-59 years with a recent coronary event.
Replacement of dietary saturated fats (from animal fats, common margarines, and shortenings) with omega 6 linoleic acid (from safflower oil and safflower oil polyunsaturated margarine). Controls received no specific dietary instruction or study foods. All non-dietary aspects were designed to be equivalent in both groups.
All cause mortality (primary outcome), cardiovascular mortality, and mortality from coronary heart disease (secondary outcomes). We used an intention to treat, survival analysis approach to compare mortality outcomes by group.
The intervention group (n=221) had higher rates of death than controls (n=237) (all cause 17.6% v 11.8%, hazard ratio 1.62 (95% confidence interval 1.00 to 2.64), P=0.05; cardiovascular disease 17.2% v 11.0%, 1.70 (1.03 to 2.80), P=0.04; coronary heart disease 16.3% v 10.1%, 1.74 (1.04 to 2.92), P=0.04). Inclusion of these recovered data in an updated meta-analysis of linoleic acid intervention trials showed non-significant trends toward increased risks of death from coronary heart disease (hazard ratio 1.33 (0.99 to 1.79); P=0.06) and cardiovascular disease (1.27 (0.98 to 1.65); P=0.07).
Advice to substitute polyunsaturated fats for saturated fats is a key component of worldwide dietary guidelines for coronary heart disease risk reduction. However, clinical benefits of the most abundant polyunsaturated fatty acid, omega 6 linoleic acid, have not been established. In this cohort, substituting dietary linoleic acid in place of saturated fats increased the rates of death from all causes, coronary heart disease, and cardiovascular disease. An updated meta-analysis of linoleic acid intervention trials showed no evidence of cardiovascular benefit. These findings could have important implications for worldwide dietary advice to substitute omega 6 linoleic acid, or polyunsaturated fats in general, for saturated fats.
Clinical trials NCT01621087.
Background
Metabolic flexibility described as “the capacity of the body to match fuel oxidation to fuel availability” has been implicated in insulin resistance. We examined fasting substrate oxidation in relation to dietary macronutrient intake, and markers of insulin resistance in otherwise healthy women, with and without a family history of diabetes mellitus (FH DM).
Methods
We measured body composition (dual x-ray absorptiometry), visceral and subcutaneous adipose tissue area (VAT, SAT, using Computerised Tomography), fasting [glucose], [insulin], [free fatty acids], [blood lipids], insulin resistance (HOMA-IR), resting energy expenditure (REE), respiratory exchange ratio(RER) and self-reported physical activity in a convenience sample of 180 women (18-45 yrs). A food frequency questionnaire was used to assess energy intake (EI) and calculate the RER: Food Quotient (FQ) ratio. Only those with EI:REE (1.05 -2.28) were included (N=140). Insulin resistance was defined HOMA-IR (>1.95).
Results
The Insulin Resistant (IR) group had higher energy, carbohydrate and protein intakes (p < 0.05) and lower PA levels than Insulin Sensitive (IS) group (P < 0.001), but there were no differences in RER or RER:FQ between groups. However, nearly 50% of the variance in HOMA-IR was explained by age, body fat %, VAT, RER:FQ and FH DM (adjusted R2 = 0.50, p < 0.0001). Insulin-resistant women, and those with FH DM had a higher RER:FQ than their counterparts (p < 0.01), independent of body fat % or distribution.
Conclusion
In these apparently healthy, weight-stable women, insulin resistance and FH DM were associated with lower fat oxidation in relation to dietary fat intake, suggesting lower metabolic flexibility.
Controversies have emerged regarding the beneficial v. detrimental effects of dietary n-6 PUFA. The alteration of the intestinal microbiota, a phenomenon termed dysbiosis, occurs during several chronic inflammatory diseases, but has not been well studied in an aged population. With present 'Western' diets predominantly composed of n-6 PUFA, we hypothesised that PUFA-rich diets cause intestinal dysbiosis in an aged population. C57BL/6 mice (aged 2 years) were fed a high-fat (40 % energy), isoenergetic and isonitrogenous diet composed of rapeseed oil, maize oil or maize oil supplemented with fish oil. We examined ileal microbiota using fluorescence in situ hybridisation and stained tissues by immunofluorescence for the presence of immune cells and oxidative stress. We observed that feeding high-fat diets rich in n-6 PUFA promoted bacterial overgrowth but depleted microbes from the Bacteroidetes and Firmicutes phyla. This corresponded with increased body mass and infiltration of macrophages and neutrophils. Fish oil supplementation (rich in long-chain n-3 PUFA like DHA and EPA) restored the microbiota and inflammatory cell infiltration and promoted regulatory T-cell recruitment. However, fish oil supplementation was associated with increased oxidative stress, evident by the increased presence of 4-hydroxynonenal, a product of lipid peroxidation. These results suggest that an n-6 PUFA-rich diet can cause dysbiosis and intestinal inflammation in aged mice. However, while fish oil supplementation on an n-6 PUFA diet reverses dysbiosis, the combination of n-6 and n-3 PUFA, like DHA/EPA, leads to increased oxidative stress, which could exacerbate gastrointestinal disorders in the elderly.
The prevalence of childhood obesity increased in the 1980s and 1990s but there were no significant changes in prevalence between 1999-2000 and 2007-2008 in the United States.
To present the most recent estimates of obesity prevalence in US children and adolescents for 2009-2010 and to investigate trends in obesity prevalence and body mass index (BMI) among children and adolescents between 1999-2000 and 2009-2010.
Cross-sectional analyses of a representative sample (N = 4111) of the US child and adolescent population (birth through 19 years of age) with measured heights and weights from the National Health and Nutrition Examination Survey 2009-2010.
Prevalence of high weight-for-recumbent length (≥95th percentile on the growth charts) among infants and toddlers from birth to 2 years of age and obesity (BMI ≥95th percentile of the BMI-for-age growth charts) among children and adolescents aged 2 through 19 years. Analyses of trends in obesity by sex and race/ethnicity, and analyses of trends in BMI within sex-specific age groups for 6 survey periods (1999-2000, 2001-2002, 2003-2004, 2005-2006, 2007-2008, and 2009-2010) over 12 years.
In 2009-2010, 9.7% (95% CI, 7.6%-12.3%) of infants and toddlers had a high weight-for-recumbent length and 16.9% (95% CI, 15.4%-18.4%) of children and adolescents from 2 through 19 years of age were obese. There was no difference in obesity prevalence among males (P = .62) or females (P = .65) between 2007-2008 and 2009-2010. However, trend analyses over a 12-year period indicated a significant increase in obesity prevalence between 1999-2000 and 2009-2010 in males aged 2 through 19 years (odds ratio, 1.05; 95% CI, 1.01-1.10) but not in females (odds ratio, 1.02; 95% CI, 0.98-1.07) per 2-year survey cycle. There was a significant increase in BMI among adolescent males aged 12 through 19 years (P = .04) but not among any other age group or among females.
In 2009-2010, the prevalence of obesity in children and adolescents was 16.9%; this was not changed compared with 2007-2008.
Our genome adapts slowly to changing conditions of existence. Many diseases of civilisation result from mismatches between our Paleolithic genome and the rapidly changing environment, including our diet. The objective of the present study was to reconstruct multiple Paleolithic diets to estimate the ranges of nutrient intakes upon which humanity evolved. A database of, predominantly East African, plant and animal foods (meat/fish) was used to model multiple Paleolithic diets, using two pathophysiological constraints (i.e. protein < 35 energy % (en%) and linoleic acid (LA) >1.0 en%), at known hunter-gatherer plant/animal food intake ratios (range 70/30-30/70 en%/en%). We investigated selective and non-selective savannah, savannah/aquatic and aquatic hunter-gatherer/scavenger foraging strategies. We found (range of medians in en%) intakes of moderate-to-high protein (25-29), moderate-to-high fat (30-39) and moderate carbohydrates (39-40). The fatty acid composition was SFA (11.4-12.0), MUFA (5.6-18.5) and PUFA (8.6-15.2). The latter was high in α-linolenic acid (ALA) (3.7-4.7 en%), low in LA (2.3-3.6 en%), and high in long-chain PUFA (LCP; 4.75-25.8 g/d), LCP n-3 (2.26-17.0 g/d), LCP n-6 (2.54-8.84 g/d), ALA/LA ratio (1.12-1.64 g/g) and LCP n-3/LCP n-6 ratio (0.84-1.92 g/g). Consistent with the wide range of employed variables, nutrient intakes showed wide ranges. We conclude that compared with Western diets, Paleolithic diets contained consistently higher protein and LCP, and lower LA. These are likely to contribute to the known beneficial effects of Paleolithic-like diets, e.g. through increased satiety/satiation. Disparities between Paleolithic, contemporary and recommended intakes might be important factors underlying the aetiology of common Western diseases. Data on Paleolithic diets and lifestyle, rather than the investigation of single nutrients, might be useful for the rational design of clinical trials.
Randomised controlled trials (RCT) of mixed n-6 and n-3 PUFA diets, and meta-analyses of their CHD outcomes, have been considered decisive evidence in specifically advising consumption of 'at least 5-10 % of energy as n-6 PUFA'. Here we (1) performed an extensive literature search and extracted detailed dietary and outcome data enabling a critical examination of all RCT that increased PUFA and reported relevant CHD outcomes; (2) determined if dietary interventions increased n-6 PUFA with specificity, or increased both n-3 and n-6 PUFA (i.e. mixed n-3/n-6 PUFA diets); (3) compared mixed n-3/n-6 PUFA to n-6 specific PUFA diets on relevant CHD outcomes in meta-analyses; (4) evaluated the potential confounding role of trans-fatty acids (TFA). n-3 PUFA intakes were increased substantially in four of eight datasets, and the n-6 PUFA linoleic acid was raised with specificity in four datasets. n-3 and n-6 PUFA replaced a combination of TFA and SFA in all eight datasets. For non-fatal myocardial infarction (MI)+CHD death, the pooled risk reduction for mixed n-3/n-6 PUFA diets was 22 % (risk ratio (RR) 0.78; 95 % CI 0.65, 0.93) compared to an increased risk of 13 % for n-6 specific PUFA diets (RR 1.13; 95 % CI 0.84, 1.53). Risk of non-fatal MI+CHD death was significantly higher in n-6 specific PUFA diets compared to mixed n-3/n-6 PUFA diets (P = 0.02). RCT that substituted n-6 PUFA for TFA and SFA without simultaneously increasing n-3 PUFA produced an increase in risk of death that approached statistical significance (RR 1.16; 95 % CI 0.95, 1.42). Advice to specifically increase n-6 PUFA intake, based on mixed n-3/n-6 RCT data, is unlikely to provide the intended benefits, and may actually increase the risks of CHD and death.
The prevalence of obesity has steadily increased over the last few decades. During this time, populations of industrialized countries have been exposed to diets rich in fat with a high content of linoleic acid and a low content of alpha-linolenic acid compared with recommended intake. To assess the contribution of dietary fatty acids, male and female mice fed a high-fat diet (35% energy as fat, linoleic acid:alpha-linolenic acid ratio of 28) were mated randomly and maintained after breeding on the same diet for successive generations. Offspring showed, over four generations, a gradual enhancement in fat mass due to combined hyperplasia and hypertrophy with no change in food intake. Transgenerational alterations in adipokine levels were accompanied by hyperinsulinemia. Gene expression analyses of the stromal vascular fraction of adipose tissue, over generations, revealed discrete and steady changes in certain important players, such as CSF3 and Nocturnin. Thus, under conditions of genome stability and with no change in the regimen over four generations, we show that a Western-like fat diet induces a gradual fat mass enhancement, in accordance with the increasing prevalence of obesity observed in humans.
Due to supporting evidence that dietary patterns may have a significant role in the maintenance of good physical performance with aging, we tested whether plasma fatty acids, saturated fatty acids (SFA), and polyunsaturated (PUFA) fatty acids are cross-sectionally associated with different physical performance and predict changes in physical performance over a 3-year period. Data were from the InCHIANTI study, a population-based study of older Italians. Plasma fatty acids were measured at enrollment (1998-2000), and outcome variables, Summary Physical Performance Battery (SPPB), and time to walk 7 meters (m) were measured at enrollment and after 3 years (2001-2004). At enrollment, 330 participants had significantly impaired lower extremity performance (defined as a SPPB score < or = 9). Adjusting for age, participants with a SPPB score > 9 had higher levels of total PUFA, n-3 PUFA, and n-6 PUFA, while significantly lower levels of SFA than those with a SPPB score < 9. Baseline SPPB scores were also associated with n-3 PUFA (beta = 0.148, p = 0.031), whereas the 7-m walk time was associated with total PUFA (beta = - 0.068, p = 0.008), after adjusting for potential confounders. Of the 884 participants with a SPPB score > 9 at baseline, 114 (12.9%) developed impaired lower extremity performance (SPPB < or = 9). In fully adjusted logistic models, baseline n-3 PUFA levels were inversely related to the risk of developing a decline in SPPB to < or = 9 (odds ratio [OR] = 0.21; 95% confidence interval [CI] = 0.08-0.53), while the n-6/n-3 ratio was associated with a higher risk of SPPB decline to < or = 9 (OR = 5.23; 95% CI = 2.02-13.51). In multivariate regression models, the n-6/n-3 ratio was associated with a longer time to walk 7 m (beta = 0.396, p = 0.037). n-3 PUFA plasma levels, which most likely reflect dietary intake, seem to protect against accelerated decline of physical performance. A higher n-6/n-3 ratio was associated with higher risk of developing poor physical performance and slower walking speed.
The effects of dietary fatty acid composition on the endogenous formation of DNA adducts of malonaldehyde (MA), the major product of lipid peroxidation, were investigated in humans. A group of 59 healthy individuals of both sexes and different ages was initially fed a milk fat-based diet rich in saturated fatty acids for 14 days. Following this initial period, after which the group was considered homogeneous with respect to diet, 30 randomly chosen subjects were given a sunflower oil-based (rich in polyunsaturated fatty acids) (SO) diet and the remaining 29 individuals a low erucic acid rapeseed oil-based (rich in monounsaturated fatty acids) (RO) diet for 25 days. The fatty acid composition of plasma lipid fractions and the level of DNA adducts of MA in total white blood cells were then determined at the end of the SO and RO dietary periods. DNA adduct levels were measured by 32p-postlabelling using reversed-phase HPLC with on-line detection of radioactivity. Higher concentrations of polyunsaturated fatty acids in plasma triglycerides and higher levels of DNA adducts of MA were found in the subjects on the SO diet when compared with those in the RO dietary group. A large inter-individual variation in adduct levels was observed. The average adduct level in the SO diet group was 7.4 +/- 8.7 adducts/10(7) nucleotides (n = 23). This level was 3.6-fold higher than that found in individuals in the RO diet group (P < 0.001). Our results, in conjunction with the mutagenic and carcinogenic properties of MA, thus suggest the interaction of lipid peroxidation products such as MA with DNA as one plausible mechanism explaining the involvement of dietary fat in carcinogenesis.
Israel has one of the highest dietary polyunsaturated/saturated fat ratios in the world; the consumption of omega-6 polyunsaturated fatty acids (PUFA) is about 8% higher than in the USA, and 10-12% higher than in most European countries. In fact, Israeli Jews may be regarded as a population-based dietary experiment of the effect of a high omega-6 PUFA diet, a diet that until recently was widely recommended. Despite such national habits, there is paradoxically a high prevalence of cardiovascular diseases, hypertension, non-insulin-dependent diabetes mellitus and obesity-all diseases that are associated with hyperinsulinemia (HI) and insulin resistance (IR), and grouped together as the insulin resistance syndrome or syndrome X. There is also an increased cancer incidence and mortality rate, especially in women, compared with western countries. Studies suggest that high omega-6 linoleic acid consumption might aggravate HI and IR, in addition to being a substrate for lipid peroxidation and free radical formation. Thus, rather than being beneficial, high omega-6 PUFA diets may have some long-term side effects, within the cluster of hyperinsulinemia, atherosclerosis and tumorigenesis.
Diet-derived lipids may influence cytokine-mediated endothelial cell dysfunction, including TNF-induced apoptosis. To test this hypothesis, oxidative stress, intracellular calcium levels, endothelial barrier function, cell viability, and apoptosis were measured in vascular endothelial cells treated with 90 microM linoleic acid (18:2, n-6) and/or 20 ng/mL TNF (100 U/mL). For short-term exposure, endothelial cells were exposed to 18:2 for 6 h or to TNF for 1.5 h. For long-term exposure, endothelial cultures were treated with 18:2 for 24 h and with TNF for 19.5 h. In cells exposed to 18:2 + TNF, pretreatment with 18:2 began 4.5 h before additional exposure to TNF for either 1.5 h (short-term exposure) or 19.5 h (long-term exposure). After treatment, endothelial cultures were washed and incubated with maintenance medium for up to 4 days. Although initial treatment with TNF or 18:2 significantly increased oxidative stress and intracellular calcium levels, only exposure to TNF induced apoptosis in cultured endothelial cells. Furthermore, the combined exposure to 18:2 + TNF potentiated TNF-induced apoptosis. Additional treatments with BAPTA-AM, n-propyl gallate, vitamin E, and with aurintricarboxylic acid partially protected against TNF- or 18:2 + TNF-induced apoptosis. The present study suggests that changes in the cellular lipid environment may markedly influence local TNF-induced events in the vascular endothelium, including endothelial cell apoptosis. Such mechanisms may play a role in the damage and death of vascular endothelial cells in atherosclerosis.
Consumption of wild ruminant fat represented the primary lipid source for pre-agricultural humans. Hence, the lipid composition of these animals' tissues may provide insight into dietary requirements that offer protection from chronic disease in modern humans.
We examined the lipid composition of muscle, brain, marrow and subcutaneous adipose tissue (AT) from 17 elk (Cervus elaphus), 15 mule deer (Odocoileus hemionus), and 17 antelope (Antilicapra americana) and contrasted them to wild African ruminants and pasture and grain-fed cattle.
Muscle fatty acid (FA) was similar among North American species with polyunsaturated fatty acids/saturated fatty acids (P/S) values from 0.80 to 1.09 and n-6/n-3 FA from 2.32 to 2.60. Marrow FA was similar among North American species with high levels (59.3-67.0%) of monounsaturated FA; a low P/S (0.24-0.33), and an n-6/n-3 of 2.24-2.88. Brain had the lowest n-6/n-3 (1.20-1.29), the highest concentration of 22:6 n-3 (elk, 8.90%; deer, 9.62%; antelope, 9.25%) and a P/S of 0.69. AT had the lowest P/S (0.05-0.09) and n-6/n-3 (2.25-2.96). Conjugated linoleic acid (CLA) isomers were found in marrow of antelope (1.5%), elk (1.0%) and deer (1.0%), in AT (deer, 0.3%; antelope, 0.3%) in muscle (antelope, 0.4%; elk, trace), but not in brain.
Literature comparisons showed tissue lipids of North American and African ruminants were similar to pasture-fed cattle, but dissimilar to grain-fed cattle. The lipid composition of wild ruminant tissues may serve as a model for dietary lipid recommendations in treating and preventing chronic disease.
Ablation of peroxisome proliferator activated receptor (PPAR) alpha, a lipid-activated transcription factor that regulates expression of beta-oxidative genes, results in profound metabolic abnormalities in liver and heart. In the present study we used PPAR alpha knockout (KO) mice to determine whether this transcription factor is essential for regulating fuel metabolism in skeletal muscle. When animals were challenged with exhaustive exercise or starvation, KO mice exhibited lower serum levels of glucose, lactate, and ketones and higher nonesterified fatty acids than wild type (WT) littermates. During exercise, KO mice exhausted earlier than WT and exhibited greater rates of glycogen depletion in liver but not skeletal muscle. Fatty acid oxidative capacity was similar between muscles of WT and KO when animals were fed and only 28% lower in KO muscles when animals were starved. Exercise-induced regulation and starvation-induced regulation of pyruvate-dehydrogenase kinase 4 and uncoupling protein 3, two classical and robustly responsive PPAR alpha target genes, were similar between WT and KO in skeletal muscle but markedly different between genotypes in heart. Real time quantitative PCR analyses showed that unlike in liver and heart, in mouse skeletal muscle PPAR delta is severalfold more abundant than either PPAR alpha or PPAR gamma. In both human and rodent myocytes, the highly selective PPAR delta agonist GW742 increased fatty acid oxidation about 2-fold and induced expression of several lipid regulatory genes, including pyruvate-dehydrogenase kinase 4 and uncoupling protein 3, responses that were similar to those elicited by the PPAR alpha agonist GW647. These results show redundancy in the functions of PPARs alpha and delta as transcriptional regulators of fatty acid homeostasis and suggest that in skeletal muscle high levels of the delta-subtype can compensate for deficiency of PPAR alpha.
The extent to which women of reproductive age are able to convert the n-3 fatty acid alpha-linolenic acid (ALNA) to eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) was investigated in vivo by measuring the concentrations of labelled fatty acids in plasma for 21 d following the ingestion of [U-13C]ALNA (700 mg). [13C]ALNA excursion was greatest in cholesteryl ester (CE) (224 (sem 70) micromol/l over 21 d) compared with triacylglycerol (9-fold), non-esterified fatty acids (37-fold) and phosphatidylcholine (PC, 7-fold). EPA excursion was similar in both PC (42 (sem 8) micromol/l) and CE (42 (sem 9) micromol/l) over 21 d. In contrast both [13C]DPA and [13C]DHA were detected predominately in PC (18 (sem 4) and 27 (sem 7) micromol/l over 21 d, respectively). Estimated net fractional ALNA inter-conversion was EPA 21 %, DPA 6 % and DHA 9 %. Approximately 22 % of administered [13C]ALNA was recovered as 13CO2 on breath over the first 24 h of the study. These results suggest differential partitioning of ALNA, EPA and DHA between plasma lipid classes, which may facilitate targeting of individual n-3 fatty acids to specific tissues. Comparison with previous studies suggests that women may possess a greater capacity for ALNA conversion than men. Such metabolic capacity may be important for meeting the demands of the fetus and neonate for DHA during pregnancy and lactation. Differences in DHA status between women both in the non-pregnant state and in pregnancy may reflect variations in metabolic capacity for DHA synthesis.
The prevalence of overweight among children in the United States increased between 1976-1980 and 1988-1994, but estimates for the current decade are unknown.
To determine the prevalence of overweight in US children using the most recent national data with measured weights and heights and to examine trends in overweight prevalence.
Survey of 4722 children from birth through 19 years of age with weight and height measurements obtained in 1999-2000 as part of the National Health and Nutrition Examination Survey (NHANES), a cross-sectional, stratified, multistage probability sample of the US population.
Prevalence of overweight among US children by sex, age group, and race/ethnicity. Overweight among those aged 2 through 19 years was defined as at or above the 95th percentile of the sex-specific body mass index (BMI) for age growth charts.
The prevalence of overweight was 15.5% among 12- through 19-year-olds, 15.3% among 6- through 11-year-olds, and 10.4% among 2- through 5-year-olds, compared with 10.5%, 11.3%, and 7.2%, respectively, in 1988-1994 (NHANES III). The prevalence of overweight among non-Hispanic black and Mexican-American adolescents increased more than 10 percentage points between 1988-1994 and 1999-2000.
The prevalence of overweight among children in the United States is continuing to increase, especially among Mexican-American and non-Hispanic black adolescents.
Polyunsaturated fatty acids (PUFAs), specifically the n-3 series, have been implicated in the prevention of various human diseases, including obesity, diabetes, coronary heart disease and stroke, and inflammatory and neurologic diseases. PUFAs function mainly by altering membrane lipid composition, cellular metabolism, signal transduction, and regulation of gene expression. PUFAs regulate the expression of genes in various tissues, including the liver, heart, adipose tissue, and brain. The role of transcription factors such as SREBP1c and nuclear receptors such as PPAR-alpha, HNF-4alpha, and LXRalpha in mediating the nuclear effects of PUFAs are addressed.
Recent research has suggested that an increased (n-3) fatty acid intake and/or increased (n-3)/(n-6) polyunsaturated fatty acid (PUFA) ratio in the diet is associated with a lower breast cancer risk. This case-control study investigated the association between intake of (n-3) and other fatty acids and the (n-3)/(n-6) PUFA ratio and breast cancer risk. After combining data from two related case-control studies in Connecticut, we had information available on a total of 1119 women (565 cases and 554 controls). Cases were all histologically confirmed, incident breast carcinoma patients. Controls were hospital-based (Yale-New Haven Hospital study site) and population-based (Tolland County study site). Information on dietary intake was obtained through a validated food-frequency questionnaire. Standard multivariate methods were used to address the independent effects of specific fatty acids, fat classes and macronutrients on breast cancer risk. In the full study population, there were no significant trends for any macronutrient/fatty acid when comparing the highest to the lowest quartile of intake. When the analysis was restricted to premenopausal women, consumption of the highest compared with the lowest quartile of the (n-3)/(n-6) PUFA ratio was associated with a nonsignificant 41% lower risk of breast cancer [odds ratio (OR) = 0.59, 95% confidence interval (CI) 0.29, 1.19, P for trend = 0.09]. A higher (n-3)/(n-6) PUFA ratio was significantly associated with a lower risk of breast cancer when the data were restricted to the Tolland County (population-based) study site; OR = 0.50, 95% CI 0.27, 0.95, P for trend = 0.02. These results are consistent with the hypothesis that a higher (n-3)/(n-6) PUFA ratio may reduce the risk of breast cancer, especially in premenopausal women.
This review addresses the hypothesis that polyunsaturated fatty acids (PUFA), particularly those of the (n-3) family, play pivotal roles as "fuel partitioners" in that they direct fatty acids away from triglyceride storage and toward oxidation, and that they enhance glucose flux to glycogen. In doing this, PUFA may protect against the adverse symptoms of the metabolic syndrome and reduce the risk of heart disease. PUFA exert their beneficial effects by up-regulating the expression of genes encoding proteins involved in fatty acid oxidation while simultaneously down-regulating genes encoding proteins of lipid synthesis. PUFA govern oxidative gene expression by activating the transcription factor peroxisome proliferator-activated receptor a. PUFA suppress lipogenic gene expression by reducing the nuclear abundance and DNA-binding affinity of transcription factors responsible for imparting insulin and carbohydrate control to lipogenic and glycolytic genes. In particular, PUFA suppress the nuclear abundance and expression of sterol regulatory element binding protein-1 and reduce the DNA-binding activities of nuclear factor Y, Sp1 and possibly hepatic nuclear factor-4. Collectively, the studies discussed suggest that the fuel "repartitioning" and gene expression actions of PUFA should be considered among criteria used in defining the dietary needs of (n-6) and (n-3) and in establishing the dietary ratio of (n-6) to (n-3) needed for optimum health benefit.
Sedentary behaviour (e.g. TV viewing, seated video game playing, prolonged sitting) has recently emerged as a distinct risk factor for cardiometabolic diseases in children and youth. This narrative review provides an overview of recent evidence in this area and highlights research gaps. Current evidence suggests that North American children and youth spend between 40% and 60% of their waking hours engaging in sedentary pursuits. Although data are lacking concerning temporal trends of objectively measured sedentary time, self-reported sedentary behaviours have increased over the past half century, with a rapid increase since the late 1990s. Excessive sedentary behaviour has been found to have independent and deleterious associations with markers of adiposity and cardiometabolic disease risk. These associations are especially consistent for screen-based sedentary behaviours (TV viewing, computer games, etc), with more conflicting findings observed for overall sedentary time. The above associations are possibly mediated by the influence of screen-based sedentary behaviours on energy intake. Although excessive sitting has been reported to have adverse acute and chronic metabolic impacts in adults, research on children is lacking. Research is particularly needed to investigate the impact of characteristics of sedentary behaviour (i.e. type/context, sedentary bout length, breaks in sedentary time, etc), as well as interventions that examine the health and behavioural impacts of sitting per se.
Unlabelled:
This study aimed to estimate intake of individual polyunsaturated fatty acids (PUFAs), identify major dietary sources of PUFAs and estimate the proportion of individuals consuming fish among US children 12-60 months of age, by age and race and ethnicity. The study employed a cross-sectional design using US National Health and Nutrition Examination Survey data. Representative sample of US population based on selected counties.
Subjects:
2496 US children aged 12-60 months. Mean daily intake of n-6 PUFAs and eicosapentaenoic acid (EPA) varied by age, with children 12-24 months of age having lower average intakes (mg or g day(-1) ) than children 49-60 months of age and the lowest n6 : n3 ratio, upon adjustment for energy intake. Docosahexaenoic acid (DHA) intake was low (20 mg day(-1) ) compared to typical infant intake and did not change with age. Compared to non-Hispanic white children, Mexican American children had higher DHA and arachidonic acid (AA) intake. In the previous 30 days, 53.7% of children ever consumed fish. Non-Hispanic black children were more likely than non-Hispanic white children to have consumed fish (64.0% vs. 53.0%). Results indicate low prevalence of fish intake and key n-3 PUFAs, relative to n-6 fatty acids, which suggests room for improvement in the diets of US children. More research is needed to determine how increasing dietary intakes of n-3 PUFAs like DHA could benefit child health.
The "Israeli Paradox" (1996) of low national health rankings despite adequate diet - attributed to high dietary n-6 polyunsaturated fatty acids (PUFA) - coincided with long-observed dichotomies between women's worse international status vs. men's advantage. This raised the possibility of a gender link to high n-6 risk potentially explaining both national phenomena. Israeli women's disadvantage was shown by worse international rankings, i.e., life expectancy (LE)--11th vs. men's 3rd-best/22 countries (2000), and 14th vs. 6th/34 (2010); and all-cause and all-cancer mortality--both 15th vs. 2nd-best/22 (2000), and 15th vs. 6th/22 and 12th vs. 2nd-best/22 (2010). Cancer mortality rates for breast were 21.8% above vs. prostate 30.4% below Eur-A (27 country) averages (2005). Gender gaps/ ratios were smaller than European Union-15 averages, i.e., for LE at birth by 34.4-26.4% (2000-2010), respectively, and at 65 years 45.9-35.3%; all-cause mortality by 43.3-33.4%, and all-cancer 65.2-58.7%. The Israeli diet was mostly close to guidelines, but n-6 intake (10-12% kcal) was much higher than recommended and traditional "Mediterranean diet" levels. Research showing females' greater potential for conversion of PUFA to long-chain PUFA (LCPUFA) may suggest increased production of n-6 eicosanoids with known proinflammatory/oxidative/carcinogenic potential. An "Israeli N-6 Gender Nutrition Paradox" hypothesis is suggested here for the first time, associating women's higher risk and lead in the national "paradox" with greater potential for n-6 conversion to pro-inflammatory/oxidative/carcinogenic eicosanoids compared to men. This may also exacerbate women's risk associated with genetic predisposition (i.e., BRCA) and/or sociopolitical stress. Global abandonment of traditional diets/foods together with increasing n-6 consumption and western disease rates emphasize the importance of considering gender nutrition in epidemiology and preventive strategies.
Purpose:
Socioeconomic inequalities in physical activity at the individual level are well reported. Whether inequalities in economic development and other macroenvironmental variables between countries are also related to physical activity at the country level is comparatively unstudied.
Methods:
We examined the relationship between country-level data on macroenvironmental factors (gross domestic product (GDP) per capita, public sector expenditure on health, percentage living in urban areas, and cars per 1000 population) with country-level physical activity prevalence obtained from previous pan-European studies. Studies that assessed leisuretime physical activity (n = 3 studies including 27 countries in adults, n = 2 studies including 28 countries in children) and total physical activity (n = 3 studies in adults including 16 countries) were analyzed separately as were studies among adults and children.
Results:
Strong and consistent positive correlations were observed between country prevalence of leisure-time physical activity and country GDP per capita in adults (average r = 0.70; all studies, P G 0.05). In multivariate analysis, country prevalence of leisure-time physical activity among adults remained associated with country GDP per capita (two of three studies) but not urbanization or educational attainment. Among school-age populations, no association was found between country GDP per capita and country prevalence of leisure-time physical activity. In those studies that assessed total physical activity (which also includes occupational and transport physical activity), no association with country GDP per capita was observed.
Conclusion:
Clear differences in national leisure-time physical activity levels throughout Europe may be a consequence of economic development. Lack of economic development of some countries in Europe may make increasing leisure-time physical activity more difficult. Further examination of the link between country GDP per capita and national physical activity levels (across leisure-time, occupational, and transport-related domains) is warranted.
Reduced availability of forage in winter is the dominant limiting factor for the isolated, predator-free caribou (Rangifer tarandus groenlandicus) population on Coats Island, Northwest Territories. Pregnant females in this population typically begin winter with large fat reserves but catabolize most of them by spring. We modelled net energy requirements of a pregnant female during two winters (1982 – 1983 and 1983 – 1984) to evaluate energy requirements for maintenance, activity, and pregnancy, and to estimate the contribution of body reserves in supplying these requirements. A secondary objective was to determine whether winter activity budgets were related to energy balance, quality of winter diets, or body condition. Estimated net energy requirements were lowest during midwinter (16 MJ/d for an average female) but increased rapidly toward spring. Maintenance was at all times the largest component of requirements, but gestation costs increased to 12 – 14% of total requirements by winter's end, and activity costs tended to increase from 3.8–4.0 MJ/d (23–25% of requirements) at the beginning of winter to 4.6–4.8 MJ/d (26 – 29% of costs) in late winter. Body reserves supplied an estimated 14.2% (1982 – 1983) and 19.2% (1983 – 1984) of overall winter requirements. The contribution from body reserves varied from 9 to 24% during different portions of the two winters and, in late winter 1982 – 1983, reserves may have been a crucial supplement at a time of decreased forage availability and rising energy costs. Caribou were least active in early winter, when they were fattest, and most active at winter's end when their energy needs were increasing. These patterns were not consistent with activity budgets of most mainland caribou, and winter activity budgets were not consistently related to either diet quality or body condition.
Previous research in our laboratory has demonstrated that the C57BL/6J (B/6J) mouse has a predisposition to develop severe obesity if placed on a high-fat diet. In the present study we assessed the role of physical activity in this phenomenon. Obesity-prone B/6J and obesity-resistant A/J mice were placed on one of four diets; high fat/high sucrose, high fat/low sucrose, low fat/high sucrose, and low fat/low sucrose. After 4 months, all animals on the high-fat diets had gained more weight than animals on the low-fat diets, and this phenomenon was greatly exaggerated in B/6J mice. Despite the fact that B/6J mice gained more weight than A/J mice on high-fat diets without consuming more calories, spontaneous motor activity was elevated in B/6J mice compared to A/J mice. There was no effect of the diets on activity either within or across strains. These data suggest that predisposition to diet-induced obesity is not explainable by reduced levels of physical activity.
It is well established that the lack of physical activity can lead to weight gain or obesity. However, there is limited information on influences of diet components on physical activity. Thus the purpose of this study was to investigate the role of major dietary components on energy expenditure by affecting nonexercise physical activity in C57BL/6J mice. All mice were assigned to 1 of the following 4 dietary groups based on their body weight and baseline physical activity; low fat/normal protein, high fat/normal protein, low fat/low protein, or low fat/high protein. After 3 mo, the highest weight gain was observed in animals fed with high-fat/normal-protein diet, and the caloric intake was significantly lower in low-fat/high-protein diet-fed mice compared to other groups. However, there were no significant changes in nonexercise physical activity during experimental periods in all groups. The respiratory quotient and energy expenditure were not significantly different among the dietary groups. These findings suggest that diet-induced obesity is not explainable by levels of physical activity and energy expenditure.
Practical Application: The understanding the link between diet and nonexercise physical activity would provide important knowledge that will potentially assist appropriate food choices to control obesity and its related health problems.
The low-density lipoprotein receptor (Ldlr) is a key molecule involved with lipid clearance. The Ldlr(-/-) mouse has been used extensively as a model for studying atherosclerosis. This study sought to characterize the energy balance phenotype of Ldlr(-/-) mice with respect to weight gain, body composition, energy expenditure (EE), glucose homeostasis, and leptin sensitivity. Adult Ldlr(-/-) mice and Ldlr(+/+) controls on a C57Bl/6J background were fed either a chow or a high-fat, high-sucrose Western-type diet (WTD) for eight wk. Physiological studies of food intake, EE, activity, insulin sensitivity, and leptin responsiveness were performed. The effect of these diet interventions on circulating leptin and on leptin gene expression was also examined. On the chow diet, Ldlr(-/-) mice had lower EE and higher activity levels relative to controls. On the WTD, Ldlr(-/-) mice gained less weight relative to Ldlr(+/+) mice, specifically gaining less fat mass. Increased thermogenesis in Ldlr(-/-) mice fed the WTD was detected. Additionally, leptin responsiveness was blunted in chow-fed Ldlr(-/-) mice, suggesting a novel role for the Ldlr pathway that extends to leptin's regulation of energy balance. In addition to its known role in lipid transport, these results demonstrate the importance of the Ldlr in energy homeostasis and suggest a direct physiological link between altered lipid transport and energy balance.
Meat consumption is inconsistently associated with development of coronary heart disease (CHD), stroke, and diabetes mellitus, limiting quantitative recommendations for consumption levels. Effects of meat intake on these different outcomes, as well as of red versus processed meat, may also vary.
We performed a systematic review and meta-analysis of evidence for relationships of red (unprocessed), processed, and total meat consumption with incident CHD, stroke, and diabetes mellitus. We searched for any cohort study, case-control study, or randomized trial that assessed these exposures and outcomes in generally healthy adults. Of 1598 identified abstracts, 20 studies met inclusion criteria, including 17 prospective cohorts and 3 case-control studies. All data were abstracted independently in duplicate. Random-effects generalized least squares models for trend estimation were used to derive pooled dose-response estimates. The 20 studies included 1 218 380 individuals and 23 889 CHD, 2280 stroke, and 10 797 diabetes mellitus cases. Red meat intake was not associated with CHD (n=4 studies; relative risk per 100-g serving per day=1.00; 95% confidence interval, 0.81 to 1.23; P for heterogeneity=0.36) or diabetes mellitus (n=5; relative risk=1.16; 95% confidence interval, 0.92 to 1.46; P=0.25). Conversely, processed meat intake was associated with 42% higher risk of CHD (n=5; relative risk per 50-g serving per day=1.42; 95% confidence interval, 1.07 to 1.89; P=0.04) and 19% higher risk of diabetes mellitus (n=7; relative risk=1.19; 95% confidence interval, 1.11 to 1.27; P<0.001). Associations were intermediate for total meat intake. Consumption of red and processed meat were not associated with stroke, but only 3 studies evaluated these relationships.
Consumption of processed meats, but not red meats, is associated with higher incidence of CHD and diabetes mellitus. These results highlight the need for better understanding of potential mechanisms of effects and for particular focus on processed meats for dietary and policy recommendations.
Body weight and energy balance can be maintained by adapting energy intake to changes in energy expenditure and vice versa, whereas short-term changes in energy expenditure are mainly caused by physical activity. This review investigates whether physical activity is affected by over- and undereating, whether intake is affected by an increase or a decrease in physical activity, and whether being overweight affects physical activity. The available evidence is based largely on studies that quantified physical activity with doubly labeled water. Overeating does not affect physical activity, while undereating decreases habitual or voluntary physical activity. Thus, it is easier to gain weight than to lose weight. An exercise-induced increase in energy requirement is typically compensated by increased energy intake, while a change to a more sedentary routine does not induce an equivalent reduction of intake and generally results in weight gain. Overweight and obese subjects tend to have similar activity energy expenditures to lean people despite being more sedentary. There are two ways in which the general population trend towards increasing body weight can be reversed: reduce intake or increase physical activity. The results of the present literature review indicate that eating less is the most effective method for preventing weight gain, despite the potential for a negative effect on physical activity when a negative energy balance is reached.
4. Print Bibliogr. na konci kapitol Na tit. listě vroč. 1989
Estimates of essential fatty acid intakes, including (n-3) PUFA, are available in pediatric populations based on limited indirect approaches. Furthermore, recommended intakes for short- and long-chain (LC) (n-3) PUFA have emerged for this population. This study provides direct quantification of fatty acid intakes in children aged 4-8 y. Identical portions of all food and natural health products consumed over 3 d were collected. Duplicate samples were analyzed for energy, macronutrients, and fatty acids, including alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) by high performance capillary GLC. The results for 41 children [25 females, 16 males; 5.8 +/- 0.2 y (mean age +/- SEM)] showed daily energy intakes of 5879 +/- 211 kJ (mean +/- SEM) and (n-3) PUFA intakes in mg/d as follows: ALA, 1161 +/- 108; EPA, 38.4 +/- 9.3; DPA, 26.3 +/- 3.9; and DHA, 54.1 +/- 11.4. Based on the Dietary Reference Intakes from the Institute of Medicine, 61% of the children met the adequate intake for ALA and 22% met the suggested adequate intake for DHA+EPA (10% of the adequate intake for ALA). These intakes were also compared with the recent Australia/New Zealand recommendations for children, where only 51% met the recommended intake for EPA+DPA+DHA. These results demonstrate a moderate shortfall in ALA intake in Canadian children and a nutrient gap for the LC (n-3) PUFA, including DHA, when comparing intakes for this population to suggested and recommended intakes.
Antidepressant drugs produce therapeutic actions and many of their side effects via blockade of the plasma membrane transporters for serotonin (SERT/SLC6A2), norepinephrine (NET/SLC6A1), and dopamine (DAT/SLC6A3). Many antidepressants block several of these transporters; some are more selective. Mouse gene knockouts of these transporters provide interesting models for possible effects of chronic antidepressant treatments. To examine the role of monoamine transporters in models of depression DAT, NET, and SERT knockout (KO) mice and wild-type littermates were studied in the forced swim test (FST), the tail suspension test, and for sucrose consumption. To dissociate general activity from potential antidepressant effects three types of behavior were assessed in the FST: immobility, climbing, and swimming. In confirmation of earlier reports, both DAT KO and NET KO mice exhibited less immobility than wild-type littermates whereas SERT KO mice did not. Effects of DAT deletion were not simply because of hyperactivity, as decreased immobility was observed in DAT+/- mice that were not hyperactive as well as in DAT-/- mice that displayed profound hyperactivity. Climbing was increased, whereas swimming was almost eliminated in DAT-/- mice, and a modest but similar effect was seen in NET KO mice, which showed a modest decrease in locomotor activity. Combined increases in climbing and decreases in immobility are characteristic of FST results in antidepressant animal models, whereas selective effects on swimming are associated with the effects of stimulant drugs. Therefore, an effect on climbing is thought to more specifically reflect antidepressant effects, as has been observed in several other proposed animal models of reduced depressive phenotypes. A similar profile was observed in the tail suspension test, where DAT, NET, and SERT knockouts were all found to reduce immobility, but much greater effects were observed in DAT KO mice. However, to further determine whether these effects of DAT KO in animal models of depression may be because of the confounding effects of hyperactivity, mice were also assessed in a sucrose consumption test. Sucrose consumption was increased in DAT KO mice consistent with reduced anhedonia, and inconsistent with competitive hyperactivity; no increases were observed in SERT KO or NET KO mice. In summary, the effects of DAT KO in animal models of depression are larger than those produced by NET or SERT KO, and unlikely to be simply the result of the confounding effects of locomotor hyperactivity; thus, these data support reevaluation of the role that DAT expression could play in depression and the potential antidepressant effects of DAT blockade.
The nocturnal activity patterns of rats changed significantly within 3 days after they were given unrestricted access to isocaloric diets in which the ratio of carbohydrate to protein was systematically varied. As the ratio increased, the rats were more continuously active. The subjects showed similar responses to variations in this ratio whether the diet contained 15 or 45 percent fat. No correlation was found between the number of calories an animal ate and its activity pattern.
The induction of breast cancer is a long process, containing a series of biological events that drive a normal mammary cell towards malignant growth. However, it is not known when the initiation of breast cancer occurs. One hypothesis is that a high estrogenic environment during the perinatal period increases subsequent breast cancer risk. There are many sources of extragonadal estrogens, particularly in the diet. The purpose of this paper is to review the evidence that a high maternal intake of dietary fats increases serum estrogens during pregnancy and increases breast cancer risk in daughters. Our animal studies show that a high maternal consumption of corn oil consisting mainly of linoleic acid (omega-6 polyunsaturated fatty acid, PUFA), increases both circulating estradiol (E2) levels during pregnancy and the risk of developing carcinogen-induced mammary tumors among the female rat offspring. A similar increase in breast cancer risk occurs in female offspring exposed to injections of E2 through their pregnant mother. Our data suggest that the mechanisms by which an early exposure to dietary fat and/or estrogens increases breast cancer risk is related to reduced differentiation of the mammary epithelial tree and increased number of mammary epithelial cell structures that are known to the sites of neoplastic transformation. These findings may reflect our data of the reduced estrogen receptor protein levels and protein kinase C activity in the developing mammary glands of female rats exposed to a high-fat diet in utero. In summary, a high dietary linoleic acid intake can elevate pregnancy estrogen levels and this, possibly by altering mammary gland morphology and expression of fat- and/or estrogen-regulated genes, can increase breast cancer risk in the offspring. If true for women, breast cancer prevention in daughters may include modulating the mother's pregnancy intake of some dietary fats.
Dietary fatty acids that are more prone to oxidation than to storage may be less likely to lead to obesity.
The aim of this study was to determine the effect of chain length, degree of unsaturation, and stereoisomeric effects of unsaturation on the oxidation of individual fatty acids in normal-weight men.
Fatty acid oxidation was examined in men consuming a weight-maintenance diet containing 40% of energy as fat. After consuming the diet for 1 wk, subjects were fed fatty acids labeled with (13)C in the methyl or carboxyl position (10 mg/kg body wt). The fatty acids fed in random order were laurate, palmitate, stearate, oleate, elaidate (the trans isomer of oleate), linoleate, and linolenate blended in a hot liquid meal. Breath samples were collected for the next 9 h and the oxidation of each fatty acid was assessed by examining liberated (13)CO(2) in breath.
Cumulative oxidation over the 9-h test ranged from a high of 41% of the dose for laurate to a low of 13% of the dose for stearate. Of the 18-carbon fatty acids, linolenate was the most highly oxidized and linoleate appeared to be somewhat conserved. (13)C recovery in breath from the methyl-labeled fatty acids was approximately 30% less than that from the carboxyl-labeled fatty acids.
In summary, lauric acid is highly oxidized, whereas the polyunsaturated and monounsaturated fatty acids are fairly well oxidized. Oxidation of the long-chain, saturated fatty acids decreases with increasing carbon number.
The forced swim test and tail suspension test are often used in laboratory practice to identify compounds that possess antidepressant-like activity. This experiment was conducted to determine whether housing conditions per se influence the response of mice in these antidepressant screening procedures. Male NIH Swiss mice were housed individually or in groups (five per cage) for 8 weeks prior to testing. After 8 weeks, the animals were exposed to the forced swim and tail-suspension tests. Group housed mice displayed high levels of immobility in the forced swim and tail suspension tests. Desipramine injection 60 min prior testing, in doses 7.5 and 15 mg/kg, produced significant reductions in the immobility time in forced swimming and tail suspension tests. Individually housed mice, when exposed to these tests, displayed lower levels of immobility with a magnitude comparable to the effect of desipramine in group housed mice. Desipramine given to individually housed mice did not reduce the duration of immobility either in the forced swim test or in the tail suspension test. These results indicate that both tests are sensitive to housing conditions. This observation suggests that long lasting group housing may be critical to the behavioral response in these preclinical screening procedures in mice.
This review addresses the hypothesis that polyunsaturated fatty acids (PUFA), particularly those of the (n-3) family, play pivotal roles as "fuel partitioners" in that they direct fatty acids away from triglyceride storage and toward oxidation, and that they enhance glucose flux to glycogen. In doing this, PUFA may protect against the adverse symptoms of the metabolic syndrome and reduce the risk of heart disease. PUFA exert their beneficial effects by up-regulating the expression of genes encoding proteins involved in fatty acid oxidation while simultaneously down-regulating genes encoding proteins of lipid synthesis. PUFA govern oxidative gene expression by activating the transcription factor peroxisome proliferator-activated receptor alpha. PUFA suppress lipogenic gene expression by reducing the nuclear abundance and DNA-binding affinity of transcription factors responsible for imparting insulin and carbohydrate control to lipogenic and glycolytic genes. In particular, PUFA suppress the nuclear abundance and expression of sterol regulatory element binding protein-1 and reduce the DNA-binding activities of nuclear factor Y, Sp1 and possibly hepatic nuclear factor-4. Collectively, the studies discussed suggest that the fuel "repartitioning" and gene expression actions of PUFA should be considered among criteria used in defining the dietary needs of (n-6) and (n-3) and in establishing the dietary ratio of (n-6) to (n-3) needed for optimum health benefit.
Activation of the vascular endothelium by dietary fatty acids may be among the most critical early events in the development of atherosclerosis. However, the specific effects of fatty acids on inflammatory responses in endothelial cells are not fully understood.
The present study focused on the induction of inflammatory genes in human endothelial cells exposed to individual dietary fatty acids. Because of the significance of nuclear factor kappaB (NF-kappaB) and activator protein 1 (AP-1) in the regulation of inflammatory gene expression, we also determined the effects of fatty acids on NF-kappaB and AP-1 transcriptional activation.
Human umbilical vein endothelial cells were exposed to dietary mono- and polyunsaturated 18-carbon fatty acids. Transcriptional activation of NF-kappaB and AP-1 was determined in human umbilical vein endothelial cells transfected with reporter constructs regulated by these transcription factors. Induction of the inflammatory genes was studied by use of reverse transcriptase-polymerase chain reaction.
Of the fatty acids studied, linoleic acid stimulated NF-kappaB and AP-1 transcriptional activation the most. In addition, treatment with this fatty acid markedly enhanced messenger RNA levels of tumor necrosis factor alpha, monocyte chemoattractant protein 1, vascular cell adhesion molecule 1, and intercellular adhesion molecule 1. Treatment with linolenic acid stimulated only a moderate induction of the genes encoding for these inflammatory mediators, and exposure to oleic acid either had no effect or resulted in decreased inflammatory gene messenger RNA. In addition, exposure to both linoleic and linolenic acids strongly stimulated induction of the phospholipid hydroperoxide glutathione peroxidase gene.
Specific unsaturated dietary fatty acids, particularly linoleic acid, can selectively stimulate the development of a proinflammatory environment within the vascular endothelium.