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2-OHOA supplementation reduced adiposity and improved cardiometabolic risk to a greater extent than n-3 PUFA in obese mice
Abstract
Objective:
We aimed to assess whether 2-hydroxyoleic acid (2-OHOA) and n-3 polyunsaturated fatty acids (PUFA) could counteract changes on adipokine secretion and cardiometabolic risk biomarkers associated with high-fat diet-induced obesity in mice.
Methods:
Female ICR/CD1 mice (8 weeks old) were divided into four groups receiving different diets (n=8/group): (1) standard chow (control) for 18 weeks; (2) 22% fat for 4 weeks + 60% fat for 14 weeks (obesogenic diet, OD); 3) OD + 2-OHOA (1500mgkg-1 diet) for the last 6 weeks (ODHO); and 4) OD+n-3 PUFA (eicosapentaenoic+docosahexaenoic acids, 1500+1500mgkg-1 diet) for the last 6 weeks (OD-N3). After 18 weeks, body weight, periovarian visceral fat, heart and liver weights were measured, as well as cardiometabolic parameters (systolic and diastolic blood pressure, blood glucose, insulin, HOMA index, triglycerides, total cholesterol, apolipoproteins A1 and E), plasma adipokines and inflammatory proteins (leptin, adiponectin, plasminogen activator inhibitor 1 [PAI1], soluble E-selectin [sE-selectin], matrix metalloproteinase-9 [MMP-9], fibrinogen, soluble intercellular adhesion molecule [sICAM] and soluble vascular adhesion molecule [sVCAM]), and secretion of pro-inflamatory cytokines and inflammatory biomarkers from periovarian adipocytes.
Results:
OD mice had greater body and heart weights, and plasma leptin, and lower adiponectin and resistin secretion from adipocytes. Supplementation with 2-OHOA reduced body and heart weights, blood pressure, triglycerides and leptin, and restored adiponectin and resistin secretion, while n-3 PUFA only reduced triglyceride levels (all P<0.05).
Conclusion:
2-OHOA supplementation was more effective in reducing adiposity, modulating adipokine secretion and ameliorating cardiometabolic risk than n-3 PUFA.
... Likewise, 3-n PUFA supplementation has been associated with recovery of the adipokine and cardiokine profile, resulting in a healthier cardio-metabolic state. In this context, studies in animal models and humans have linked supplements administration with a significant reduction in leptin (227,228), follistatin-like 1 (229) and BNP levels (230), and adiponectin increase (231). Finally, polyphenols such as lycopene, resveratrol and curcumin have also been linked to improved inflammatory and adipokine profile, body composition and cardiac fibrosis/ hypertrophy in study subjects (232)(233)(234)(235). ...
Adipose tissue (AT) biology is linked to cardiovascular health since obesity is associated with cardiovascular disease (CVD) and positively correlated with excessive visceral fat accumulation. AT signaling to myocardial cells through soluble factors known as adipokines, cardiokines, branched-chain amino acids and small molecules like microRNAs, undoubtedly influence myocardial cells and AT function via the endocrine-paracrine mechanisms of action. Unfortunately, abnormal total and visceral adiposity can alter this harmonious signaling network, resulting in tissue hypoxia and monocyte/macrophage adipose infiltration occurring alongside expanded intra-abdominal and epicardial fat depots seen in the human obese phenotype. These processes promote an abnormal adipocyte proteomic reprogramming, whereby these cells become a source of abnormal signals, affecting vascular and myocardial tissues, leading to meta-inflammation, atrial fibrillation, coronary artery disease, heart hypertrophy, heart failure and myocardial infarction. This review first discusses the pathophysiology and consequences of adipose tissue expansion, particularly their association with meta-inflammation and microbiota dysbiosis. We also explore the precise mechanisms involved in metabolic reprogramming in AT that represent plausible causative factors for CVD. Finally, we clarify how lifestyle changes could promote improvement in myocardiocyte function in the context of changes in AT proteomics and a better gut microbiome profile to develop effective, non-pharmacologic approaches to CVD.
... Different works reported that PUFA ingestion ameliorates APN deficiency in obese patients [75]. Moreover, Redondo Useros et al. using an animal model have demonstrated that 2-hydroxyoleic acid, synthetic hydroxylated fatty acid, decreases body weight restoring APN levels [76] (Table 3). ...
It is now established that adipose tissue, skeletal muscle, and heart are endocrine organs and secrete in normal and in pathological conditions several molecules, called, respectively, adipokines, myokines, and cardiokines. These secretory proteins constitute a closed network that plays a crucial role in obesity and above all in cardiac diseases associated with obesity. In particular, the interaction between adipokines, myokines, and cardiokines is mainly involved in inflammatory and oxidative damage characterized obesity condition. Identifying new therapeutic agents or treatment having a positive action on the expression of these molecules could have a key positive effect on the management of obesity and its cardiac complications. Results from recent studies indicate that several nutritional interventions, including nutraceutical supplements, could represent new therapeutic agents on the adipo-myo-cardiokines network. This review focuses the biological action on the main adipokines, myokines and cardiokines involved in obesity and cardiovascular diseases and describe the principal nutraceutical approaches able to regulate leptin, adiponectin, apelin, irisin, natriuretic peptides, and follistatin-like 1 expression.
Objective
In the present study, we evaluated the effect of biochanin A (BCA) on high-fat diet (HFD)-induced obesity cardiomyopathy.
Methods
BCA (10 mg/kg body weight) was administered to HFD-induced obese rats for 30 days, and its effect on anthropometrical, morphological, plasma cardiac, and inflammatory biomarkers, along with cardiac lipid profiles was assessed.
Results
Supplementation of HFD to rats significantly increased body mass index, obesity index parameters, and cardiac lipid profile along with notable oxidative stress and inflammation. Additionally, BCA treatment in obese rats demonstrated a superior therapeutic action by restoring the altered parameters to almost normal levels. Simultaneously, BCA increased the activities and mRNA expressions of enzymatic antioxidants by upregulating the Nrf-2 pathway and inhibiting the NF-κB cascade.
Conclusion
BCA may attenuate obesity and its associated cardiomyopathy by suppressing oxidative stress and inflammation through activation of the Nrf-2 pathway and inhibition of NF-κB activation.
Obesity and its related diseases have been associated with oxidative stress. Thus, the search for nutritional strategies to ameliorate oxidative stress in obese individuals seems important. We hypothesized that the supplementation with monounsaturated (2-hydroxyoleic acid (2-OHOA)) and with combined n-3 polyunsaturated (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) fatty acids would ameliorate oxidative stress in different organs, including brain, liver, lungs, and kidneys of adult diet-induced obese (DIO) mice. Adult female ICR-CD1 mice were fed a high-fat diet (HFD) for 14 weeks. During the last 6 weeks of HFD feeding, one group of DIO mice received the same HFD, supplemented with 1500 mg of 2-OHOA per kg of HFD and another group with 1500 mg of EPA and 1500 mg of DHA per kg of HFD. At the end of the experiment, several parameters of oxidative stress were assessed. The supplementation with 2-OHOA or with EPA and DHA in DIO mice was able to revert oxidative stress, enhancing the activities of catalase and glutathione reductase, as well as diminishing the activity of xanthine oxidase, the concentration of thiobarbituric acid reactive substances (TBARS) and the ratio between oxidized glutathione and reduced glutathione in several organs. These reached similar values to those of control mice, which were fed a standard diet. These data suggest that supplementation with 2-OHOA and with EPA and DHA could be an effective nutritional intervention to restore an appropriate redox state in DIO mice.
The modulation of the intestinal microbiota by high-fat diet (HFD) has a major impact on both immunological and metabolic functions of the host. Taking this into consideration, the aim of this contribution is to review the impact of HFD on microbiota profile and small intestinal physiology before and after the onset of obesity and its metabolic complications. Evidence from animal studies suggest that before the onset of obesity and its metabolic complications, HFD induces intestinal dysbiosis - encompassing changes in composition balance and massive redistribution with bacteria occupying intervillous spaces and crypts - associated with early physiopathological changes, predominantly in the ileum, such as low-grade inflammation, decreased antimicrobial peptides expression, impaired mucus production, secretion and layer's thickness, and decreased expression of tight junction proteins. With time, major inflammatory signals (e.g. toll-like receptor-4 dependent) become activated, thereby stimulating proinflammatory cytokines secretion in the small intestine. This inflammatory state might subsequently exacerbate disruption of the mucus layer barrier and increase epithelial permeability of the small intestine, thereby creating an environment that facilitates the passage of bacterial components (e.g. lipopolysaccharide, peptidoglycan and flagellin) and metabolites from the intestinal lumen to the circulation (e.g. secondary bile acids) and peripheral tissues (i.e. leaky gut), eventually promoting the development of systemic inflammation, obesity, adiposity, insulin resistance and glucose intolerance preceding hyperglycemia. Although the mechanisms are still not completely understood, prebiotics, probiotics, polyphenols peroxisome proliferator-activated receptor-γ agonists (such as rosiglitazone) and exercise have been shown to reverse HFD-induced intestinal phenotype and to attenuate the severity of obesity and its associated metabolic complications.
Several studies and reviews regarding the supplementation of omega-3 LC-PUFAs have been developed during the last years. Indeed, the evidence states that high doses omega-3 LC-PUFAs produce a small but significant decrease in blood pressure in older and hypertensive subjects. Due to the increasing interest in the benefits of LC-PUFAs, we aimed to evaluate the scientific evidence provided in the past five years (2012-2016) on the effects of the intake of omega-3 LC-PUFAs on cardiovascular risk factors such as inflammation and oxidative stress, through a systematic review in PubMed database. Twenty-eight articles were related to cardiovascular disease (CVD) and are included in this systematic review. The studies included healthy subjects and CVD patients; we included the number of subjects, type of study, type and doses of omega-3 LC-PUFAs, primary outcomes, and results. The use of omega-3 LC-PUFAs for ameliorating CVD risk factors can be recommended. However, the administration of omega-3 does not seem to show any benefit for the management of CVD or associated complications.
Adipose tissue secretes a variety of bioactive substances that are associated with chronic inflammation, insulin resistance, and an increased risk of type 2 diabetes mellitus. While resistin was first known as an adipocyte-secreted hormone (adipokine) linked to obesity and insulin resistance in rodents, it is predominantly expressed and secreted by macrophages in humans. Epidemiological and genetic studies indicate that increased resistin levels are associated with the development of insulin resistance, diabetes, and cardiovascular disease. Resistin also appears to mediate the pathogenesis of atherosclerosis by promoting endothelial dysfunction, vascular smooth muscle cell proliferation, arterial inflammation, and the formation of foam cells. Thus, resistin is predictive of atherosclerosis and poor clinical outcomes in patients with cardiovascular disease and heart failure. Furthermore, recent evidence suggests that resistin is associated with atherogenic dyslipidemia and hypertension. The present review will focus on the role of human resistin in the pathogeneses of inflammation and obesity-related diseases.
Purpose of review:
The aim of this review is to overview the pathophysiological role of adipocytokines in atherogenesis, focusing on their potential role as biomarkers of coronary disease.
Recent findings:
Several lines of evidence indicated adipose tissue not only as depot but rather as an endocrine organ. In this context, the balance between pro- and anti-inflammatory adipocytokines has been shown to critically regulate vascular homeostasis in both physiological and pathophysiological conditions. Overweight and obesity are characterized by dysfunctional adipose tissue and then the prevalence of pro-inflammatory mediators, with a detrimental effect on vascular health. As opposite to adiponectin, pro-inflammatory adipocytokines, such as leptin and resistin, promote endothelial dysfunction and inflammatory processes involved in atherosclerotic plaque progression and vulnerability. Therefore, many adipocytokines have been investigated as potential biomarkers of cardiovascular (CV) risk, but their role has not yet been clearly established. Furthermore, the perivascular adipose tissue recently emerged as a critical modulator of atherosclerotic processes, due to the close interaction with the underlying vascular tissue. The ongoing discovery of new adipocytokines and the complex pathophysiological role of the different adipose tissue depots strongly contribute to define the complexity of adipocytokines network. Understanding those complex interactions may allow determining new potential biomarkers of CV risk and potential therapeutic targets.
Obesity is an excessive accumulation of body fat that may be harmful to health. Today, obesity is a major public health problem, affecting in greater or lesser proportion all demographic groups. Obesity is estimated by body mass index (BMI) in a clinical setting, but BMI reports neither body composition nor the location of excess body fat. Deaths from cardiovascular diseases, cancer and diabetes accounted for approximately 65% of all deaths, and adiposity and mainly abdominal adiposity are associated with all these disorders. Adipose tissue could expand to inflexibility levels. Then, adiposity is associated with a state of low-grade chronic inflammation, with increased tumor necrosis factor-α and interleukin-6 release, which interfere with adipose cell differentiation, and the action pattern of adiponectin and leptin until the adipose tissue begins to be dysfunctional. In this state the subject presents insulin resistance and hyperinsulinemia, probably the first step of a dysfunctional metabolic system. Subsequent to central obesity, insulin resistance, hyperglycemia, hypertriglyceridemia, hypoalphalipoproteinemia, hypertension and fatty liver are grouped in the so-called metabolic syndrome (MetS). In subjects with MetS an energy balance is critical to maintain a healthy body weight, mainly limiting the intake of high energy density foods (fat). However, high-carbohydrate rich (CHO) diets increase postprandial peaks of insulin and glucose. Triglyceride-rich lipoproteins are also increased, which interferes with reverse cholesterol transport lowering high-density lipoprotein cholesterol. In addition, CHO-rich diets could move fat from peripheral to central deposits and reduce adiponectin activity in peripheral adipose tissue. All these are improved with monounsaturated fatty acid-rich diets. Lastly, increased portions of ω-3 and ω-6 fatty acids also decrease triglyceride levels, and complement the healthy diet that is recommended in patients with MetS.
Dietary supplementation with marine omega-3 polyunsaturated fatty acids (n-3 PUFA) can have beneficial effects on a number of risk factors for cardiovascular disease (CVD). We compared the effects of two n-3 PUFA rich food supplements (freeze-dried Odontella aurita and fish oil) on risk factors for CVD. Male rats were randomly divided into four groups of six animals each and fed with the following diets: control group (C) received a standard diet containing 7 % lipids; second group (HF high fat) was fed with a high-fat diet containing 40 % lipids; third group (HFFO high fat+fish oil) was fed with the high-fat diet supplemented with 0.5 % fish oil; and fourth group (HFOA high fat+O. aurita) received the high-fat diet supplemented with 12 % of freeze-dried O. aurita. After 8 weeks rats fed with the high-fat diet supplemented with O. aurita displayed a significantly lower bodyweight than those in the other groups. Both the microalga and the fish oil significantly reduced insulinemia and serum lipid levels. O. aurita was more effective than the fish oil in reducing hepatic triacyglycerol levels and in preventing high-fat diet-induced steatosis. O. aurita and fish oil also reduced platelet aggregation and oxidative status induced by high fat intake. After an OA supplementation, the adipocytes in the HFOA group were smaller than those in the HF group. Freeze-dried O. aurita showed similar or even greater biological effects than the fish oil. This could be explained by a potential effect of the n-3 PUFA but also other bioactive compounds of the microalgae.
Background
International comparisons of dietary intake are an important source of information to better understand food habits and their relationship to nutrition related diseases. The objective of this study is to compare food intake of Brazilian adults with American adults identifying possible dietary factors associated with the increase in obesity in Brazil.
Methods
This research used cross-national analyses between the United States and Brazil, including 5,420 adults in the 2007–2008 What We Eat In America, National Health and Nutrition Examination Survey and 26,390 adults in the 2008–2009 Brazilian Household Budget Survey, Individual Food Intake. Dietary data were collected through 24 h recalls in the U.S. and through food records in Brazil. Foods and beverages were combined into 25 food categories. Food intake means and percentage of energy contribution by food categories to the population’s total energy intake were compared between the countries.
Results
Higher frequencies of intake were reported in the United States compared to Brazil for the majority of food categories except for meat, rice and rice dishes; beans and legumes; spreads; and coffee and tea. In either country, young adults (20-39 yrs) had greater reports of meat, poultry and fish mixed dishes; pizza and pasta; and soft drinks compared to older adults (60 + yrs). Meat, poultry and fish mixed dishes (13%), breads (11%), sweets and confections (8%), pizza and pasta (7%), and dairy products (6%) were the top five food category sources of energy intake among American adults. The top five food categories in Brazil were rice and rice dishes (13%), meat (11%), beans and legumes (10%), breads (10%), and coffee and tea (6%). Thus, traditional plant-based foods such as rice and beans were important contributors in the Brazilian diet.
Conclusion
Although young adults had higher reports of high-calorie and nutrient-poor foods than older adults in both countries, Brazilian young adults did not consume a diet similar to Americans, indicating that it is still possible to reverse the current trends of incorporating Western dietary habits in Brazil.
Different dietary fat and energy subtypes have an impact on both the metabolic health and the intestinal microbiota population of the host. The present study assessed the impact of dietary fat quality, with a focus on dietary fatty acid compositions of varying saturation, on the metabolic health status and the intestinal microbiota composition of the host. C57BL/6J mice (n 9-10 mice per group) were fed high-fat (HF) diets containing either (1) palm oil, (2) olive oil, (3) safflower oil or (4) flaxseed/fish oil for 16 weeks and compared with mice fed low-fat (LF) diets supplemented with either high maize starch or high sucrose. Tissue fatty acid compositions were assessed by GLC, and the impact of the diet on host intestinal microbiota populations was investigated using high-throughput 16S rRNA sequencing. Compositional sequencing analysis revealed that dietary palm oil supplementation resulted in significantly lower populations of Bacteroidetes at the phylum level compared with dietary olive oil supplementation (P< 0·05). Dietary supplementation with olive oil was associated with an increase in the population of the family Bacteroidaceae compared with dietary supplementation of palm oil, flaxseed/fish oil and high sucrose (P< 0·05). Ingestion of the HF-flaxseed/fish oil diet for 16 weeks led to significantly increased tissue concentrations of EPA, docosapentaenoic acid and DHA compared with ingestion of all the other diets (P< 0·05); furthermore, the diet significantly increased the intestinal population of Bifidobacterium at the genus level compared with the LF-high-maize starch diet (P< 0·05). These data indicate that both the quantity and quality of fat have an impact on host physiology with further downstream alterations to the intestinal microbiota population, with a HF diet supplemented with flaxseed/fish oil positively shaping the host microbial ecosystem.
Omega-3 PUFA of marine origin reduce adiposity in animals fed a high-fat diet. Our aim was to learn whether EPA and DHA could
limit development of obesity and reduce cellularity of adipose tissue and whether other dietary FA could influence the effect
of EPA/DHA. Weight gain induced by composite high-fat diet in C57BL/6J mice was limited when the content of EPA/DHA was increased
from 1 to 12% (wt/wt) of dietary lipids. Accumulation of adipose tissue was reduced, especially of the epididymal fat. Low
ratio of EPA to DHA promoted the effect. A higher dose of EPA/DHA was required to reduce adiposity when admixed to diets that
did not promote obesity, the semisynthetic high-fat diets rich in EFA, either α-linolenic acid (ALA, 18∶3 n−3, the precursor
of EPA and DHA) or linoleic (18∶2 n−6) acid. Quantification of adipose tissue DNA revealed that except for the diet rich in
ALA the reduction of epididymal fat was associated with 34–50% depression of tissue cellularity, similar to the 30% caloric
restriction in the case of the high-fat composite diet. Changes in plasma markers and adipose gene expression indicated improvement
of lipid and glucose metabolism due to EPA/DHA even in the context of the diet rich in ALA. Our results document augmentation
of the antiadipogenic effect of EPA/DHA during development of obesity and suggest that EPA/DHA could reduce accumulation of
body fat by limiting both hypertrophy and hyperplasia of fat cells. Increased dietary intake of EPA/DHA may be beneficial
regardless of the ALA intake.
No dietary recommendations for monounsaturated fatty acids (MUFA) are given by the National Institute of Medicine, the United States Department of Agriculture, European Food and Safety Authority and the American Diabetes Association. In contrast, the Academy of Nutrition and Dietetics, and the Canadian Dietetic Association both promote <25% MUFA of daily total energy consumption, while the American Heart Association sets a limit of 20% MUFA in their respective guidelines. The present review summarizes systematic reviews and meta-analyses of randomized controlled trials and cohort studies investigating the effects of MUFA on cardiovascular and diabetic risk factors, cardiovascular events and cardiovascular death. Electronic database Medline was searched for systematic reviews and meta-analyses using "monounsaturated fatty acids", "monounsaturated fat", and "dietary fat" as search terms with no restriction to calendar date or language. Reference lists and clinical guidelines were searched as well. Sixteen relevant papers were identified. Several studies indicated an increase of HDL-cholesterol and a corresponding decrease in triacylglycerols following a MUFA-rich diet. The effects on total and LDL-cholesterol appeared not consistent, but no detrimental effects on blood lipids were observed. Values for systolic and diastolic blood pressure were found to be reduced both during short- and long-term protocols using high amounts of MUFA as compared to low-MUFA diets. In type 2 diabetic subjects, MUFA exerted a hypoglycemic effect and reduced glycosylated hemoglobin in the long term. Data from meta-analyses exploring evidence from long-term prospective cohort studies provide ambiguous results with respect to the effects of MUFA on risk of coronary heart disease (CHD). One meta-analysis reported an increase in CHD events, however, most meta-analyses observed a lesser number of cases in participants subjected to a high-MUFA protocol. Although no detrimental side effects of MUFA-rich diets were reported in the literature, there still is no unanimous rationale for MUFA recommendations in a therapeutic regimen. Additional long-term intervention studies are required to characterized efficacy and effectiveness of recommending MUFA-rich diet among general and clinical populations.
Over 50 years of research has sought to define the role dietary fat plays in cardiovascular disease (CVD) risk. Although optimal dietary fat quantity has been keenly pursued over past decades, attention has recently centered on the value of dietary fat quality. The purpose of the present review is to provide a critical assessment of the current body of evidence surrounding efficacy of dietary monounsaturated fatty acids (MUFA) for reduction of traditional risk factors defining metabolic syndrome (MetS) and CVD. Due to existing and emerging research on health attributes of MUFA rich diets, and to the low prevalence of chronic disease in populations consuming MUFA rich Mediterranean diets, national dietary guidelines are increasingly recommending dietary MUFA, primarily at the expense of saturated fatty acids (SFA). Consumption of dietary MUFA promotes healthy blood lipid profiles, mediates blood pressure, improves insulin sensitivity and regulates glucose levels. Moreover, provocative newer data suggest a role for preferential oxidation and metabolism of dietary MUFA, influencing body composition and ameliorating the risk of obesity. Mounting epidemiological and human clinical trial data continue to demonstrate the cardioprotective activity of the MUFA content of dietary fat. As the debate on the optimal fatty acid composition of the diet continues, the benefit of increasing MUFA intakes, particularly as a substitute for dietary SFA, deserves considerable attention.
We investigated the effects of eicosapentaenoic acid (EPA) on prevention (P) and reversal (R) of high saturated-fat (HF) diet-induced obesity and glucose-insulin homeostasis. Male C57BL/6J mice were fed low-fat (LF; 10% energy from fat), HF (45% energy from fat), or a HF-EPA-P (45% energy from fat; 36 g/kg EPA) diet for 11 wk. A 4th group was initially fed HF for 6 wk followed by the HF-EPA-R diet for 5 wk. As expected, mice fed the HF diet developed obesity and glucose intolerance. In contrast, mice fed the HF-EPA-P diet maintained normal glucose tolerance despite weight gain compared with the LF group. Whereas the HF group developed hyperglycemia and hyperinsulinemia, both HF-EPA groups (P and R) exhibited normal glycemia and insulinemia. Further, plasma adiponectin concentration was lower in the HF group but was comparable in the LF and HF-EPA groups, suggesting a role of EPA in preventing and improving insulin resistance induced by HF feeding. Further analysis of adipose tissue adipokine levels and proteomic studies in cultured adipocytes indicated that dietary EPA supplementation of HF diets was associated with reduced adipose inflammation and lipogenesis and elevated markers of fatty acid oxidation. In C57BL/6J mice, EPA minimized saturated fat-induced insulin resistance and this is in part mediated by its effects on fatty acid oxidation and inflammation.
Leptin is currently believed to control body composition largely, if not entirely, via hypothalamic receptors that regulate food intake and thermogenesis. Here we demonstrate direct extraneural effects of leptin to deplete fat content of both adipocytes and nonadipocytes to levels far below those of pairfed controls. In cultured pancreatic islets, leptin lowered triglyceride (TG) content by preventing TG formation from free fatty acids (FFA) and by increasing FFA oxidation. In vivo hyperleptinemia, induced in normal rats by adenovirus gene transfer, depleted TG content in liver, skeletal muscle, and pancreas without increasing plasma FFA or ketones, suggesting intracellular oxidation. In islets of obese Zucker Diabetic Fatty rats with leptin receptor mutations, leptin had no effect in vivo or in vitro. The TG content was ≈20 times normal, and esterification capacity was increased 3- to 4-fold. Thus, in rats with normal leptin receptors but not in Zucker Diabetic Fatty rats, nonadipocytes and adipocytes esterify FFA, store them as TG, and later oxidize them intracellularly via an “indirect pathway” of intracellular fatty acid metabolism controlled by leptin. By maintaining insulin sensitivity and preventing islet lipotoxicity, this activity of leptin may prevent adipogenic diabetes.
In our previous studies, chronic treatment of rats with a new beta 3-adrenoceptor agonist, CL 316,243, retarded diet-induced obesity and promoted thermogenesis in young animals and reversed established diet-induced obesity in older animals that continued to eat a high fat diet. Reversal of obesity was associated with shrinking of enlarged white adipocytes but the number of mature white adipocytes, which had not been increased by the diet, was not reduced. Drug-treatment induced appearance of abundant brown adipocytes in white adipose tissue (WAT) depots as well as hypertrophy of brown adipose tissue (BAT) in both lean and diet-induced obese rats.
To find out whether the known hyperplasia of white adipocytes in the obese fa/fa rat could be reversed by CL 316,243-treatment and whether the grossly enlarged WAT depots of the obese fa/fa rat contain precursors to brown adipocytes.
CL 316,243 infusion (1 mg/kg/d) reduced abdominal fat. The loss of fat was due to a decrease in white adipocyte size, with no loss of the markedly elevated number of adipocytes in the fa/fa rats. Resting metabolic rate increased by 40% in lean rats, by 70% in fa/fa rats. Food intake decreased in the hyperphagic fa/fa rats but did not change in lean rats, in both lean and fa/fa rats, a marked increase in protein content of retroperitoneal WAT was associated with appearance of abundant densely-stained brown adipocytes expressing uncoupling protein (UCP) but total number of cells (from DNA content) actually decreased. Hyperinsulinemia and hyperglycemia of fa/fa rats were reduced by treatment, indicating improved sensitivity to insulin.
Abundant precursors to brown adipocytes are present in WAT depots of fa/fa rats and much of the exaggerated increase in resting metabolic rate induced by CL 316,243 occurs in these cells. This beta 3-adrenoceptor agonist is an effective anti-obesity and anti-diabetic agent in fa/fa rats. It does not bring about disappearance of mature white adipocytes but does bring about a remodelling of WAT, with a marked change in cell composition.
To better understand the molecular basis of dietary obesity, we examined adipose tissue genes differentially expressed in an obesity model using DNA microarray analysis.
We assessed the expression level of over 12,500 transcripts in epididymal fat pads from (cafeteria) obese and control rats with the aid of the array technology.
Cafeteria (obese) rats weighed 50% more and had 2.5-fold higher levels of epididymal fat and elevated levels of circulating leptin. Adipose genes differentially expressed in obese and control rats were categorized into five groups: macronutrient metabolism, transcription factors, hormone receptor and signal transduction, redox and stress proteins, and cellular cytoskeleton. Interestingly, the expression levels of a number of genes involved in lipid metabolism such as glycerol-3-phosphate dehydrogenase, stearoyl coenzyme A desaturase, together with the transcription factors implicated in adipocyte differentiation (CAAT/enhancer binding protein-alpha and peroxisome proliferator-activated receptor-gamma), were significantly increased in obese animals compared with control. The most up-regulated transcripts were the ob (49.2-fold change) and the fatty acid-binding protein genes (15.7- fold change). In contrast, genes related to redox and stress protein were generally down-regulated in obese animals compared with the control.
Our study showed that in diet-induced obesity, the expression levels of some important genes implicated in lipid metabolism were up-regulated, whereas those related to redox and stress protein were down-regulated in obese animals compared with control. This pattern of gene expression may occur in human obesity cases after high-fat intake.
Recent studies have shown that diets rich in monounsaturated fatty acids (MUFAs) from olive oil, a natural source of oleic acid, have beneficial effects on blood pressure (BP) in hypertensive patients. With this in mind, we investigated whether a synthetic derivative of the MUFA oleic acid, 2-hydroxyoleic acid (2-OHOA), was capable of regulating the BP of Sprague-Dawley rats. Intraperitoneal and oral administration of 2-OHOA to rats induced significant and sustained decreases in BP in a time-dependent manner. Without affecting heart rate, treatments for 7 days provoked reductions in systolic BP of 20 to 26 mm Hg. At the molecular level, the density of Galpha(s), but not Galpha(i2) or Galpha(o), increased in membranes from the hearts and aortas of 2-OHOA-treated rats, whereas in heart membranes, the density of Galpha(q)/11 and protein kinase Calpha proteins was also augmented. These molecular alterations were reflected in the increase in cAMP levels after Galpha(s) protein and beta-adrenergic receptor stimulation. On the contrary, inhibitory hormones reduced adenylyl cyclase activity to the same extent in 2-OHOA-treated rats as in vehicle-treated ones. Our results indicate that cardiovascular tissues from 2-OHOA-treated rats exhibited increased cAMP production in response to Galpha(s) activation, which might be attributed to enhanced expression of Galpha(s) proteins. As a result of this change, a significant reduction in systolic BP was observed. Therefore, BP can be lowered by administration of 2-OHOA, which might represent the first member of a new family of antihypertensive drugs.
Resistin was originally reported as an adipose tissue-specific hormone that provided a link between obesity and diabetes. Resistin protein level was elevated in obese mice and decreased by insulin-sensitizing thiazolidinediones. Immunoneutralization of resistin improved insulin sensitivity in diet-induced obese mice, while the administration of exogenous resistin induced insulin resistance. More recently, we have shown that ablation of the resistin gene in mice decreased fasting glucose through impairment of gluconeogenesis, while resistin treatment in these knockout mice increased hepatic glucose production. However, the link between resistin and glucose homeostasis has been questioned by studies demonstrating reduced, rather than increased, resistin mRNA expression in obese and diabetic mice. To better understand the regulation of resistin, we developed a sensitive and specific RIA resistin that could accurately measure serum resistin levels in several mouse models. We show that while resistin mRNA is indeed suppressed in obese mice, the circulating resistin level is significantly elevated and positively correlated with insulin, glucose, and lipids. Both resistin mRNA expression and protein levels in Lep(ob/ob) mice are suppressed by leptin treatment in parallel with reductions in glucose and insulin. In wild-type mice, serum resistin increases after nocturnal feeding, concordant with rising levels of insulin. Resistin mRNA and protein levels decline in parallel with glucose and insulin during fasting and are restored after refeeding. We performed clamp studies to determine whether resistin is causally related to insulin and glucose. Adipose resistin expression and serum resistin increased in response to hyperinsulinemia and further in response to hyperglycemia. Taken together, these findings suggest that the nutritional regulation of resistin and changes in resistin gene expression and circulating levels in obesity are mediated, at least in part, through insulin and glucose.
Objective:
To discuss present knowledge about adiponectin hormone.
Design:
Review of existing literature.
Setting and results:
Adiponectin is one of the most interesting cytokines associated with obesity, although its physiological role remains to be fully clarified. Adiponectin is a 247-amino acid protein that contains four differentiable domains. Contrary to most adipose-related cytokines, adiponectin levels are surprisingly lower in obese than in lean humans. Women have been found to have significantly higher adiponectin plasma concentrations than men. Further research is needed in order to identify new polymorphisms which contribute to explain the potential role of adiponectin in obesity and related pathologies. Considering the anti-inflammatory properties of adiponectin and the fact that it is negatively associated with adiposity, this cytokine could be one of the links between obesity and inflammation. The main mechanisms of action of adiponectin are directed to a protective role against atherogenic and insulin resistance processes. Research has revealed interesting new functions far beyond metabolism, such as immunity, cancer and bone formation. Contrary to all adipose-related proteins, adiponectin decreases with obesity. Most of the contradictory data surrounding adiponectin are related to plasma values and their relationship with body fat, gender differences and insulin resistance. There are important confounding results regarding the mechanisms of action and functions of adiponectin, especially in relation to insulin resistance and inflammation.
To investigate the relationship between chemical structure and physiological effect, the efficacy and the molecular mechanisms involved in the reduction of body weight by C18 fatty acids (stearic, elaidic, oleic, linoleic and 2-hydroxyoleic acids (2-OHOA)).
Ad libitum fed, lean Wistar Kyoto rats treated orally with up to 600 mg kg(-1) of the fatty acids or vehicle every 12 h for 7 days. Besides, starved rats and rats pairfed to the 2-OHOA-treated group served as additional controls under restricted feeding conditions.
Body weight, food intake, weight of various fat depots, plasma leptin, hypothalamic neuropeptides, uncoupling proteins (UCP) in white (WAT) and brown adipose tissue (BAT) and phosphorylation level of cyclic AMP (cAMP) response element-binding protein (CREB) in WAT.
Only treatment with oleic acid and 2-OHOA induced body weight loss (3.3 and 11.4%, respectively) through reduction of adipose fat mass. Food intake in these rats was lower, although hypothalamic neuropeptide and plasma leptin levels indicated a rise in orexigenic status. Rats pairfed to the 2-hydroxyoleic group only lost 6.3% body weight. UCP1 expression and phosphorylation of CREB was drastically increased in WAT, but not BAT of 2-OHOA-treated rats, whereas no UCP1 expression could be detected in WAT of rats treated with oleic acid.
Both cis-configured monounsaturated C18 fatty acids (oleic acid and 2-OHOA) reduce body weight, but the introduction of a hydroxyl group in position 2 drastically increases loss of adipose tissue mass. The novel molecular mechanism unique to 2-hydroxyoleic, but not oleic acid, implies induction of UCP1 expression in WAT by the cAMP/PKA pathway-dependent transcription factor CREB, most probably as part of a transdifferentiation process accompanied by enhanced energy expenditure.
Aim:
To examine whether a low-carbohydrate, high unsaturated/low saturated fat diet (LC) improves glycemic control and cardiovascular disease (CVD) risk factors in overweight and obese patients with type 2 diabetes (T2D).
Methods:
115 adults with T2D (mean[SD]; BMI:34.6[4.3]kg/m2 , age:58[7]yrs, HbA1c:7.3[1.1]%) were randomized to one of two planned energy-matched, hypocaloric diets combined with aerobic/resistance exercise (1hr,3d/wk) for 2 years:(1) LC:14% energy as carbohydrate, 28% protein, 58% fat [<10% saturated fat]) or (2) low fat, high-carbohydrate, low glycemic index diet (HC):53% CHO, 17% protein, 30% fat [<10% saturated fat]). HbA1c, glycemic variability [GV], anti-glycemic medication effect score [MES; calculated based on the potency and dosage of the diabetes medication], weight, body composition, CVD and renal risk markers were assessed before and after intervention.
Results:
Sixty-one (LC=33, HC=28) participants completed the study. Reductions in weight (estimated marginal mean [95% CI];LC:-6.8[-8.8,-4.7],HC:-6.6 [-8.8,-4.5]kg), body fat (LC:-4.3[-6.2,-2.4], HC:-4.6[-6.6,-2.7]kg), blood pressure (LC:-2.0[-5.9,1.8]/-1.2[-3.6,1.2], HC:-3.2[-7.3,0.9]/-2.0[-4.5,0.5]mmHg), HbA1c (LC:-0.6[-0.9,-0.3],HC:-0.9[-1.2,-0.5]%) and fasting glucose (LC:0.3[-0.4,1.0],HC:-0.4[-1.1,0.4]mmol/L) were similar between groups (P≥0.09). Compared to HC, the LC achieved greater reductions in diabetes medication use (MES;LC:-0.5[-0.6,-0.3],HC:-0.2[-0.4,-0.02]units;P=0.03), GV: Continuous Overall Net Glycemic Action calculated every 1-hr (LC:-0.4 [-0.6,-0.3],HC:-0.1 [-0.1,0.2]mmol/L;P=0.001), and 4-hr (LC:-0.9[-1.3,-0.6], HC:-0.2[-0.6,0.1]mmol/L;P=0.02); triglycerides (LC:-0.1[-0.3,0.2],HC:0.1[-0.2,0.3]mmol/L;P=0.001); and maintained HDL-C levels (LC:0.02[-0.05,0.1],HC:-0.1[-0.1,0.01]mmol/L;P=0.004), but had similar changes in LDL-C (LC:0.2[-0.1,0.5],HC:0.1[-0.2,0.4]mmol/L;P=0.85), brachial artery flow mediated dilatation (LC:-0.5[-1.5,0.5],HC:-0.4[-1.4,0.7]%;P=0.73), eGFR and albuminuria.
Conclusions:
Both diets achieved comparable weight loss and HbA1c reductions. The LC sustained greater reductions in diabetes medication requirements, and improvements in diurnal blood glucose stability and blood lipid profile, with no adverse renal effects, suggesting greater T2D management optimisation.
Trial registration:
http://www.anzctr.org.au/, ANZCTR No. ACTRN12612000369820.
New Findings
What is the central question of this study?
Evidence is growing for the link between obesity, immune dysfunction and oxidative stress, but it is still not known how the properties and functions of the spleen and splenic leucocytes are affected.
What is the main finding and its importance?
Obesity led to premature immunosenescence, manifested as oxidative stress and changes in leucocyte functions in mouse spleen. The oleic acid derivative 2‐hydroxyoleate and, to a lesser extent, a combination of eicosapentaenoic and docosahexaenoic acids could reverse most of the observed alterations, suggesting a potential therapeutic tool for obesity‐related immune dysfunction and redox imbalance.
We aimed to investigate the effects of obesity on oxidative stress and leucocyte function in the mouse spleen and to assess whether supplementation with 2‐hydroxyoleic acid (2‐OHOA) or n ‐3 polyunsaturated fatty acids (PUFAs) could reverse those effects. Female ICR/CD1 mice (8 weeks old, n = 24) received an obesogenic diet (22% fat for 4 weeks and 60% fat for 14 weeks). After 6 weeks, mice were divided into the following three groups ( n = 8 per group): no supplementation; 2‐OHOA supplementation (1500 mg kg ⁻¹ of diet); and n ‐3 PUFA supplementation (eicosapentaenoic acid and docosahexaenoic acid, 1500 + 1500 mg kg ⁻¹ of diet). Eight mice were fed the standard diet for the whole duration of the study (control group). At the end of the experiment, the following variables were assessed in spleens: levels of reduced (GSH) and oxidized glutathione (GSSG), GSH/GSSG, xanthine oxidase activity, lipid peroxidation, lymphocyte chemotaxis, natural killer activity and mitogen (concanavalin A and lipopolysaccharide)‐induced lymphocyte proliferation. Obese animals presented higher GSSG levels ( P = 0.003), GSSG/GSH ratio ( P = 0.013), lipid peroxidation ( P = 0.004), xanthine oxidase activity ( P = 0.015) and lymphocyte chemotaxis ( P < 0.001), and lower natural killer activity ( P = 0.003) and proliferation in response to concanavalin A ( P < 0.001) than control mice. 2‐Hydroxyoleic acid totally or partly reversed most of the changes (body weight, fat content, GSSG levels, GSH/GSSG, lipid peroxidation, chemotaxis and proliferation, all P < 0.05), whereas n ‐3 PUFAs reversed the increase in xanthine oxidase activity ( P = 0.032). In conclusion, 2‐OHOA or, to a lesser extent, n ‐3 PUFAs could ameliorate the oxidative stress and alteration of leucocyte function in the spleens of obese mice. Our findings support a link between obesity and immunosenescence and suggest a potential therapeutic tool for obesity‐related immune dysfunction.
The Mediterranean diet and consumption of olive oil have been connected in several studies with longevity and a reduced risk of morbidity and mortality. Lifestyle, such as regular physical activity, a healthy diet, and the existing social cohesion in Southern European countries have been recognised as candidate protective factors that may explain the Mediterranean Paradox. Along with some other characteristics of the Mediterranean diet, the use of olive oil as the main source of fat is common in Southern European countries. The benefits of consuming olive oil have been known since antiquity and were traditionally attributed to its high content in oleic acid. However, it is now well established that these effects must also be attributed to the phenolic fraction of olive oil with its anti-oxidant, anti-inflammatory and anti-microbial activities. The mechanisms of these activities are varied and probably interconnected. For some activities of olive oil phenolic compounds, the evidence is already strong enough to enable the legal use of health claims on foods. This review discusses the health effects of olive oil phenols along with the possibilities of communicating these effects on food labels.
Consumption of a high-fat diet (HFD), which is associated with chronic 'low-grade' systemic inflammation, alters the gut microbiota (GM). The aim of the present study was to investigate the ability of an oleic acid-derived compound (S1) and a combination of n-3 fatty acids (EPA and DHA, S2) to modulate both body weight and the GM in HFD-induced obese mice. A total of eighty mice were fed either a control diet or a HFD, non-supplemented or supplemented with S1 or S2. At week 19, faeces were collected in order to analyse the GM. Group-specific primers for accurate quantification of several major bacterial groups from faecal samples were assayed using quantitative PCR. The HFD induced an increase in body weight, which was reduced by supplementation with S1. Furthermore, S1 supplementation markedly increased total bacterial density and restored the proportions of bacteria that were increased (i.e. clostridial cluster XIVa and Enterobacteriales) or decreased (i.e. Bifidobacterium spp.) during HFD feeding. S2 supplementation significantly increased the quantities of Firmicutes (especially the Lactobacillus group). Correlation analysis revealed that body weight correlated positively with the phylum Firmicutes and clostridial cluster XIVa, and negatively with the phylum Bacteroidetes. In conclusion, the consumption of a HFD induced changes in the faecal microbiota, which were associated with the appearance of an obese phenotype. Supplementation of the HFD with S1 counteracted HFD-induced gut dysbiosis, together with an improvement in body weight. These data support a role for certain fatty acids as interesting nutrients related to obesity prevention.
Obesity shares with most chronic diseases the presence of an inflammatory component, which accounts for the development of metabolic disease and other associated health alterations. This inflammatory state is reflected in increased circulating levels of pro-inflammatory proteins, and it occurs not only in adults but also in adolescents and children. The chronic inflammatory response has its origin in the links existing between the adipose tissue and the immune system. Obesity, like other states of malnutrition, is known to impair the immune function, altering leucocyte counts as well as cell-mediated immune responses. In addition, evidence has arisen that an altered immune function contributes to the pathogenesis of obesity. This review attempts to briefly comment on the various plausible explanations that have been proposed for the phenomenon: (1) the obesity-associated increase in the production of leptin (pro-inflammatory) and the reduction in adiponectin (anti-inflammatory) seem to affect the activation of immune cells; (2) NEFA can induce inflammation through various mechanisms (such as modulation of adipokine production or activation of Toll-like receptors); (3) nutrient excess and adipocyte expansion trigger endoplasmic reticulum stress; and (4) hypoxia occurring in hypertrophied adipose tissue stimulates the expression of inflammatory genes and activates immune cells. Interestingly, data suggest a greater impact of visceral adipose tissue and central obesity, rather than total body fat, on the inflammatory process. In summary, there is a positive feedback loop between local inflammation in adipose tissue and altered immune response in obesity, both contributing to the development of related metabolic complications.
We reviewed available evidence for cardiovascular effects of n-3 polyunsaturated fatty acid (PUFA) consumption, focusing on long chain (seafood) n-3 PUFA, including their principal dietary sources, effects on physiological risk factors, potential molecular pathways and bioactive metabolites, effects on specific clinical endpoints, and existing dietary guidelines. Major dietary sources include fatty fish and other seafood. n-3 PUFA consumption lowers plasma triglycerides, resting heart rate, and blood pressure and might also improve myocardial filling and efficiency, lower inflammation, and improve vascular function. Experimental studies demonstrate direct anti-arrhythmic effects, which have been challenging to document in humans. n-3 PUFA affect a myriad of molecular pathways, including alteration of physical and chemical properties of cellular membranes, direct interaction with and modulation of membrane channels and proteins, regulation of gene expression via nuclear receptors and transcription factors, changes in eicosanoid profiles, and conversion of n-3 PUFA to bioactive metabolites. In prospective observational studies and adequately powered randomized clinical trials, benefits of n-3 PUFA seem most consistent for coronary heart disease mortality and sudden cardiac death. Potential effects on other cardiovascular outcomes are less-well-established, including conflicting evidence from observational studies and/or randomized trials for effects on nonfatal myocardial infarction, ischemic stroke, atrial fibrillation, recurrent ventricular arrhythmias, and heart failure. Research gaps include the relative importance of different physiological and molecular mechanisms, precise dose-responses of physiological and clinical effects, whether fish oil provides all the benefits of fish consumption, and clinical effects of plant-derived n-3 PUFA. Overall, current data provide strong concordant evidence that n-3 PUFA are bioactive compounds that reduce risk of cardiac death. National and international guidelines have converged on consistent recommendations for the general population to consume at least 250 mg/day of long-chain n-3 PUFA or at least 2 servings/week of oily fish.
Lipoic acid (LA) is an antioxidant with therapeutic potential on several diseases such as diabetes and obesity. Hyperleptinemia and oxidative stress play a major role in the development of obesity-linked diseases. The aim of this study was to examine in vivo and in vitro the effects of LA on leptin production, as well as to elucidate the mechanisms and signalling pathways involved in LA actions.
Dietary supplementation with LA decreased both circulating leptin, and adipose tissue leptin mRNA in rats. Treatment of 3T3-L1 adipocytes with LA caused a concentration-dependent inhibition of leptin secretion and gene expression. Moreover, LA stimulated the anaerobic utilization of glucose to lactate, which negatively correlated with leptin secretion. Furthermore, LA enhanced phosphorylation of Sp1 and inhibited Sp1 transcriptional activity in 3T3-L1 adipocytes. Moreover, LA inhibited Akt phosphorylation, a downstream target of phosphatidylinositol 3-kinase (PI3K). Treatment with the PI3K inhibitor LY294002 mimicked LA actions, dramatically inhibiting both leptin secretion and gene expression and stimulating Sp1 phosphorylation.
All of these data suggest that the phosphorylation of Sp1 and the accompanying reduced DNA-binding activity are likely to be involved in the inhibition of leptin induced by LA, which could be mediated in part by the abrogation of the PI3K/Akt pathway.
Obesity plays a causative role in the pathogenesis of the metabolic syndrome. Adipokines may link obesity to its co-morbidities. Most adipokines with pro-inflammatory properties are overproduced with increasing adiposity, while some adipokines with anti-inflammatory or insulin-sensitizing properties, like adiponectin are decreased. This dysregulation of adipokine production may promote obesity-linked metabolic disorders and cardiovascular disease. Besides considering adipokines, this review will also highlight the cellular key players and molecular mechanisms involved in adipose inflammation. Targeting the changes in the cellular composition of adipose tissue, the underlying molecular mechanisms, and the altered production of adipokines may have therapeutic potential in the management of the metabolic syndrome.
This article discusses specific dietary factors as well as dietary patterns that affect the major coronary heart disease (CHD) lipid risk factors (ie, LDL-C, HDL-C, and TG). Based on a very large evidence base, it is clear that diet and lifestyle practices can markedly affect these major CHD lipid risk factors, and consequently decrease CHD risk substantively.
Leptin is a 16-kDa protein secreted by white adipose tissue that is primarily involved in the regulation of food intake and energy expenditure. Plasma leptin concentration is proportional to the amount of adipose tissue and is markedly increased in obese individuals. Recent studies suggest that leptin is involved in cardiovascular complications of obesity, including arterial hypertension. Acutely administered leptin has no effect on blood pressure, probably because it concomitantly stimulates the sympathetic nervous system and counteracting depressor mechanisms such as natriuresis and nitric oxide (NO)-dependent vasorelaxation. By contrast, chronic hyperleptinemia increases blood pressure because these acute depressor effects are impaired and/or additional sympathetic nervous system-independent pressor effects appear, such as oxidative stress, NO deficiency, enhanced renal Na reabsorption and overproduction of endothelin. Although the cause-effect relationship between leptin and high blood pressure in humans has not been demonstrated directly, many clinical studies have shown elevated plasma leptin in patients with essential hypertension and a significant positive correlation between leptin and blood pressure independent of body adiposity both in normotensive and in hypertensive individuals. In addition, leptin may contribute to end-organ damage in hypertensive individuals such as left ventricular hypertrophy, retinopathy and nephropathy, independent of regulating blood pressure. Here, current knowledge about the role of leptin in the regulation of blood pressure and in the pathogenesis of arterial hypertension is presented.
High-fat (HF)-diet rodent models have contributed significantly to the analysis of the pathophysiology of the insulin resistance syndrome, but their phenotype varies distinctly between different studies. Here, we have systematically compared the metabolic and molecular effects of different HF with varying fatty acid compositions. Male Wistar rats were fed HF diets (42% energy; fat sources: HF-L - lard; HF-O - olive oil; HF-C - coconut fat; HF-F - fish oil). Weight, food intake, whole-body insulin tolerance and plasma parameters of glucose and lipid metabolism were measured during a 12-week diet course. Liver histologies and hepatic gene expression profiles, using Affymetrix GeneChips, were obtained. HF-L and HF-O fed rats showed the most pronounced obesity and insulin resistance; insulin sensitivity in HF-C and HF-F was close to normal. Plasma omega-3 polyunsaturated fatty acid (omega-3-PUFA) and saturated fatty acid (C(12)-C(14), SFA) levels were elevated in HF-F and HF-C animals respectively. The liver histologies showed hepatic steatosis in HF-L, HF-O and HF-C without major inflammation. Hepatic SREBP1c-dependent genes were upregulated in these diets, whereas PPARalpha-dependent genes were predominantly upregulated in HF-F fed rats. We detected classical HF effects only in diets based on lard and olive oil (mainly long-chain, saturated (LC-SFA) and monounsaturated fatty acids (MUFA)). PUFA- or MC-SFA-rich diets did not induce insulin resistance. Diets based on LC-SFA and MUFA induced hepatic steatosis with SREBP1c activation. This points to an intact transcriptional hepatic insulin effect despite resistance to insulin's metabolic actions.
The metabolic syndrome (MetS) is a multiplex risk factor for cardiovascular disease. The syndrome develops through interplay of obesity and metabolic susceptibility.
This article addresses whether the MetS construct has clinical utility. POSITION: The National Cholesterol Education Program and other organizations have proposed that the MetS can be recognized clinically by a clustering of simple clinical measures including waist circumferences, blood pressure, triglycerides, high-density lipoproteins, and glucose. People with this clustering have most or all of the components of the MetS. Identifying the MetS has several advantages. It discovers persons who are at increased risk for cardiovascular disease. A diagnosis focuses more clinical attention on the underlying causes, notably obesity and other lifestyle factors; it thereby reinforces the utility of lifestyle changes in clinical practice. A diagnosis further informs physicians on choice and intensity of drug therapy for elevated cholesterol, aspirin prophylaxis, and blood pressure and glucose control. The introduction of the MetS has led to a large number of epidemiological, metabolic, and genetic studies that have heightened our understanding of the condition's prevalence and pathogenesis. It has been a stimulus to the development of new drugs or drug combinations that will modify multiple risk factors simultaneously.
This author holds that the MetS counts as a multiplex cardiovascular risk factor that is clinically useful and will lead to advances in diagnosis and treatment of an important cause of cardiovascular disease.
This review focuses on the possible association between types of fatty acids and weight change. It examines the biological plausibility underlining these associations and the evidence obtained to date from clinical trials and epidemiological studies. Animal studies have shown that dietary short- and medium-chain fatty acids compared to long-chain fatty acids appear to promote weight loss. Similarly, monounsaturated fatty acids (MUFAs) appear to favor weight loss compared to saturated fatty acids (SFAs) in human studies. The structure of fatty acids seems to affect their degree of oxidation and deposition. Although results are conflicting, human studies follow the general trend reported in animal studies. These trials suggest that some fatty acids are prone to oxidation and some others lead to fat storage when comparing isocaloric diets. For instance, n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic and docosahexaenoic acids are preferentially oxidizied to other PUFA but results remain inconsistent. Epidemiological studies concerning this issue reported that total dietary fat, which includes MUFA, PUFA, and SFA could increase the risk of obesity, but results are few and conflicting. The rising biological plausibility linking dietary fat quality and risk of obesity, together with the rather recent addition of fatty acids content in food composition tables, support the need for major epidemiological studies in that area.