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Influence of food texture on energy metabolism and adiposity in male rats
Experimental Physiology
Abstract
New findings:
What is the central question of this manuscript? What is the effect of food texture on fat accumulation, lipogenesis and proinflammatory factors in the adipose tissue and on energy balance in male rats? What is the main finding and its importance? Calorie intake and fat accumulation in rats fed soft pellets ad libitum increased, but their body weight did not. The data suggest that, even when BMI is normal, frequent consumption of soft food may contribute to the development of lifestyle-related diseases.
Abstract:
Dietary factors such as food texture are known to affect feeding behaviour and energy metabolism. We recently found that rats fed soft pellets (SPs) on a 3 h restricted feeding schedule showed glucose intolerance, insulin resistance with disruption of insulin signalling, and hyperplasia of pancreatic β-cells, even though there were no differences in energy intake and body weight between rats fed control pellets (CPs) and rats fed SPs. We investigated the effect of food texture on fat accumulation, lipogenesis and proinflammatory factors in the mesenteric fat, as well as on energy balance in male rats fed CPs or SPs. We used 7-week-old Wistar rats that were randomly divided into two groups, ad libitum fed either CPs or SPs for 27 weeks. Body weight and calorie intake were monitored once a week throughout the experiment. The calorie intake, lipogenesis and fat accumulation of the rats fed SPs increased, whereas their body weight did not. Additionally, SP rats used their fat mainly as a source of energy and increased their energy expenditure. Our data suggest that the habit of frequently eating soft food causes visceral fat accumulation without an increase in body weight. Further investigations using soft-textured foods could lead to the development of appropriate interventions for non-overweight patients with lifestyle-related diseases.
... Although many studies have been conducted on the effects of diet on the body, they have focused on the components or quantity of diet, while few have examined the effects of food texture. A soft pellet (SP) diet has recently been reported to increase body weight and fat, as well as insulin resistance and adipogenesis in rodents (Bae et al. 2014;Han et al. 2018). These findings suggest that the texture of food, or consequently the act of chewing, profoundly impacts energy homeostasis. ...
... Research on food texture is limited even though many healthy foods are socially popular. It was reported that rats fed SP under free-feeding conditions had an increase in body weight and body fat mass, resulting in abnormal glucose tolerance and lipogenesis (Bae et al. 2014;Han et al. 2018), suggesting that SP may contribute to obesity and diabetes. The authors also reported an increased locomotor activity in SP-fed rats (Han et al. 2018). ...
... It was reported that rats fed SP under free-feeding conditions had an increase in body weight and body fat mass, resulting in abnormal glucose tolerance and lipogenesis (Bae et al. 2014;Han et al. 2018), suggesting that SP may contribute to obesity and diabetes. The authors also reported an increased locomotor activity in SP-fed rats (Han et al. 2018). ...
Diet alters the function and composition of small intestinal epithelial cells, making the relationship between diet and the intestine a focus of much research. This study aimed to clarify the effects of a soft diet on the small intestine. We fed mice a soft pellet diet (SP) and a control hard pellet diet (CD) for 14 days and examined changes in the epithelial cells of the small intestine. We found that the body weights of SP‐fed mice were lower than those of CD‐fed mice. SP did not alter the length of the small intestine, crypt to villus, or the number of Paneth and Goblet cells, but decreased the expression of small intestinal epithelial cell markers. We also found that SP did not change the copy number of mitochondrial DNA, but decreased the mRNA expression of mitochondrial metabolism genes in SP‐fed mice. In addition, we found that E‐cadherin, a cell adhesion factor, was decreased in SP‐fed mice and that the composition of their microbiota was different from that of CD mice. Our study suggests that SP may impair the homeostasis of small intestine epithelial cells, reinforcing the need for further research on how food texture affects intestinal health.
... Recent data showed that calorie intake, lipogenesis, and fat accumulation is higher in rats fed soft pellets ad libitum for 27 wk. Interestingly, the authors observed that energy expenditure, evaluated by oxygen consumption and locomotor activity, was higher in rats fed soft pellets than in control rats, which may explain the similarities in body weight between the 2 groups [122]. However, to our knowledge, no longitudinal clinical study analyzing dietary texture and general health conditions in childhood has been conducted. ...
Infancy and early childhood are important periods for the development of food choices and eating preferences that are tracked into adult life, influencing weight gain, body composition, and metabolism and ultimately affecting the balance between health and disease. In this narrative review, we discuss studies focused on the effects of fetal programming and early food experiences, highlighting recent advances in the discovery of factors that contribute to the development of food preferences and eating behavior. Food preference can be influenced by early direct contact with flavors, textures, and aromas, as well as by environmental adversities during early development. Evidence suggests that exposure to intrauterine growth restriction is associated with increased preferences for highly palatable foods, such as those rich in carbohydrates and fats, over the life course. Early flavor experiences, whether from amniotic fluid or human milk, may also shape the development of food preferences. Finally, children are more likely to accept textures that they are able to manipulate, and early exposure to a range of textures facilitates the acceptance of foods of various textures later on. Improving dietary habits during gestation (fetal) and postnatal periods is of critical importance for the establishment of positive eating habits and healthy growth in infants and should be an important focus of primary prevention efforts.
... In a similar trial, the consumption of softer pellets by rodents was associated with increased ad libitum energy intake and adipose tissue accumulation, but no difference in body weight. 241 This suggests a specific metabolic effect of frequently consuming softer foods that require less mastication, which is consistently seen to contribute to a higher energy intake and greater adiposity, despite an equivalent body weight. Therefore, even when changes to body weight are minimal, there may be an increased risk of diet-related chronic disease associated with the sustained consumption of softer diets ( Figure 6.3). ...
This is the first book for some years that provides a comprehensive overview of food oral processing. It includes fundamental chapters at the beginning of each section to aid the understanding of the later more specific oral processing chapters. The field is rapidly developing, and the systems researched in the context of food oral processing become increasingly complex and therefore the fundamental sections include information on how to build complex food systems.
The main coverage includes the biomechanics of swallowing, the biophysics of mouthfeel and texture as well as the biochemistry of flavours and how food microstructures can be manipulated. It contains up-to-date research findings, looking at consumer preferences and the response to these preferences by food process technologists and those developing new foods.
The book will be of interest to postgraduate students and researchers in academia and industry who may be from very diverse backgrounds ranging from food process engineers to functional food developers and professionals concerned with swallowing and taste disorders.
Diet is an important contributor to human healthiness. The firmness of food can impact both the quantity of chews and the duration of chewing. The significance of mastication has been firmly established in recent years, with studies indicating that it has several favorable impacts on the entire body. Stroke constitutes a serious risk to human health because of its high morbidity, disability, recurrence, and fatality rates. As a result, the objective of this study was to assess the prolonged soft-diet impact on both body weight and lipid profiles with and without brain ischemia-reperfusion (IR). In addition, we estimated the brain oxidative and inflammatory states with the histological appearance, and an immunohistochemical investigation was accomplished on inducible nitric oxide synthase (iNOS) and caspase 3 (Casp-3). The current study found that rats fed an SD had higher body weight and dyslipidemia, as well as significantly higher levels of oxidative and inflammatory brain markers, as compared to rats on an ordinary laboratory diet. Feeding with soft diet (SD) also notably worsened the deficiencies in overall antioxidant capabilities. Moreover, chronic consumption of SD up-regulated the brain IR-induced over-expression of iNOS and Casp-3. The histological analysis of brain tissue in IR rats revealed a significant exacerbation of the loss of normal architecture and infiltration of inflammatory cells due to pre-SD diet. In conclusion, chronic SD intake is hazardously obesogenic, with Higher cardiac risk factors resulting from disrupted lipid metabolism. The findings may raise concerns regarding the potential health risks associated with prolonged intake of SD in humans, particularly among individuals who are obese or have neurological or other organ-related conditions.
Background
Type 2 diabetes (T2D) is characterized by insulin resistance and defective insulin secretion. Previously, we found that rats fed soft pellets (SPs) on a 3-h restricted schedule over 14 wk demonstrated glucose intolerance and insulin resistance with disruption of insulin signaling.
Objectives
This study aims to determine 1) the time required for an SP diet to induce insulin resistance, and 2) whether the metabolic derangements in rats fed SPs can be reversed by changing to a standard control diet.
Methods
We performed glucose tolerance tests and calculated the homeostasis model assessment of insulin resistance (HOMA-IR) to evaluate the insulinemic response to glucose and assess insulin resistance in nonobese male rats fed control pellets (CPs) or SPs on a 3–h restricted schedule (10:00–13:00) for 4 and 9 wk. At 11 wk, we switched half of the insulin-resistant SP group to CPs [soft-to-control pellets (SCPs)] and after an additional 11 wk evaluated changes in glucose and lipid metabolism across the 3 groups.
Results
The glucose tolerance test results in the SP and CP rats did not differ at 4 or 9 wk. The insulin levels in the SP group were higher than in the CP group at both time points (P < 0.05). The HOMA-IR was significantly higher in the SP rats at 9 wk compared with the controls (P < 0.05). At 22 wk, the HOMA-IR, blood glucose levels at 30 min after initiating feeding, hepatic glucose metabolism, and lipid synthesis in rats fed SPs continuously were significantly greater than in those fed CPs (P < 0.05); however, these values in the SCP rats did not differ from those in the CP rats.
Conclusions
A continuous diet of soft-textured, readily absorbable food may be an important and reversible underlying driver in T2D pathogenesis.
There appears to be no attempt to categorize the specific classes of behavior that the tactile system underpins. Awareness of how an organism uses touch in their environment informs understanding of its versatility in non-verbal communication and tactile perception. This review categorizes the behavioral functions underpinned by the tactile sense, by using three sources of data: (1) Animal data, to assess if an identified function is conserved across species; (2) Human capacity data, indicating whether the tactile sense can support a proposed function; and (3) Human impaired data, documenting the impacts of impaired tactile functioning (e.g., reduced tactile sensitivity) for humans. From these data, three main functions pertinent to the tactile sense were identified: Ingestive Behavior; Environmental Hazard Detection and Management; and Social Communication. These functions are reviewed in detail and future directions are discussed with focus on social psychology, non-verbal behavior and multisensory perception.
Introduction:
Scientific evidence indicates that eating slowly reduces food and energy intake. However, few investigations have studied the effect of techniques and strategies that modify eating speed on intake. The objective of this study is to analyze the relationship between these techniques and food and/or energy intake. Therefore, a systematic review of 15 human studies and a meta-analysis of 7 studies with 11 experimental and 1 observational manipulations were carried out. Only the results of two conditions were included, "slow" vs. "fast" of eating speed and ingestion. The estimation of the effect was expressed in OR with a 95 % CI under a random effects model, and heterogeneity was assessed with I2. Publication bias was also assessed with a funnel plot and Egger's linear regression test. The results indicate that eating slowly is a protective factor (OR = 0.73) from excessive intake. Additionally, eating small bites with a small spoon (OR = 0.315), serving food preparations on separate plates (OR = 0.860 and OR = 0.831), using a vibrotactile feedback fork (OR = 0.847), and eating hard-textured foods (OR = 0.831) are the techniques and strategies that modify eating speed and decrease food or energy intake. The present study confirms the premise that eating slowly can reduce excessive food and energy intake.
To the Editor: Skinner et al. (Oct. 1 issue)(1) describe the increased prevalence of cardiometabolic risk factors among overweight or obese children who were included in the National Health and Nutrition Examination Survey (NHANES) from 1999 through 2012. The investigators excluded children with normal weight from the study analysis. Research has suggested the presence of a metabolically obese, normal-weight phenotype even in childhood.(2) It is important to look at additional risk factors, such as abdominal obesity, family history, birth weight, and ethnic predisposition, in order to comprehensively assess the future cardiovascular risk among children.(3) The data provided in the article . . .
Guanylin (Gn), a bioactive peptide, and its receptor, guanylyl cyclase-C (GC-C), are primarily present in the intestine and maintain homeostasis in body fluids. Recently, rats whose macrophages overexpress Gn and GC-C were found to be resistant to diet-induced obesity. Considering that obesity is strongly related to a chronic inflammatory state in white adipose tissues, it is possible that Gn-GC-C macrophages contribute to the regulation of inflammation. In the present study, we investigated the inflammatory state of mesenteric fat in rats transgenic for both Gn and GC-C (double-transgenic [dTg] rats) by evaluating the levels of cyclic GMP (cGMP), a second messenger of Gn-GC-C, cGMP-dependent protein kinase (PKG), and phosphorylated vasodilator-stimulated phosphoprotein (VASP), a target protein of PKG. The levels of cGMP in dTg rats was higher than in WT rats fed the same diet. Although there were no significant differences in levels of PKG and phosphorylated VASP between WT and dTg rats fed a standard diet (STD), these levels in dTg rats fed a high fat diet (HFD) were markedly increased compared with levels in HFD WT rats. Furthermore, mRNA levels of proinflammatory factors in mesenteric fat were lower in HFD dTg rats than in HFD WT rats and were similar to levels in STD WT and dTg rats. These results indicate that the Gn-GC-C system in macrophages regulates the cGMP-PKG-VASP pathway and controls obesity through the downregulation of proinflammatory factors.
Sympathetic tone is well recognised as being implicit in cardiovascular control. It is less readily acknowledged that activation of the sympathetic nervous system is integral in energy homeostasis and can exert profound metabolic effects. Accumulating data from animal and human studies suggest that central sympathetic overactivity plays a pivotal role in the aetiology and complications of several metabolic conditions that can cluster to form the Metabolic Syndrome (MetS). Given the known augmented risk for type 2 diabetes, cardiovascular disease, and premature mortality associated with the MetS understanding the complex pathways underlying the metabolic derangements involved has become a priority. Many factors have been proposed to contribute to increased sympathetic nerve activity in metabolic abnormalities including obesity, impaired baroreflex sensitivity, hyperinsulinemia, and elevated adipokine levels. Furthermore there is mounting evidence to suggest that chronic sympathetic overactivity can potentiate two of the key metabolic alterations of the MetS, central obesity and insulin resistance. This review will discuss the regulatory role of the sympathetic nervous system in metabolic control and the proposed pathophysiology linking sympathetic overactivity to metabolic abnormalities. Pharmacological and device-based approaches that target central sympathetic drive will also be discussed as possible therapeutic options to improve metabolic control in at-risk patient cohorts.
Food texture is known to affect energy metabolism. Although feeding with soft pellets or via a tube is known to cause increases in body weight, it is unclear how different food textures influence energy metabolism. Here, we investigated the effects of two different food textures on energy balance and glucose and lipid metabolism in male Wistar rats. We fed the rats soft pellets (SP) or control pellets (CP) on a 3-h restricted feeding schedule for 14 weeks and examined their energy intake, body weight, and energy expenditure. The levels of gastrointestinal hormones, glucose, and insulin were investigated at pre-, mid, and post-feeding. Glucose tolerance and insulin tolerance tests were conducted, and the expressions of molecules involved in the insulin signaling system or lipogenesis in the liver were examined. Pancreatic islets were histologically investigated by using anti-insulin and anti-Ki-67 antibodies. Furthermore, the expression of microRNA-33 (miR-33), which regulates insulin receptor substance-2, was examined in the liver and circulating blood. There were no significant differences in energy intake, body weight, or gastrointestinal hormone levels between the SP and CP rats; however, the SP rats showed glucose intolerance and insulin resistance with disruption of insulin signaling. Increases in lipogenic factors and miR-33 expression were also found in the SP rats. The numbers of insulin-positive areas and Ki-67-positive cells of SP rats were significantly increased. The present study shows that a soft food texture causes diabetes without obesity, so differences in food texture may be an important factor in type 2 diabetes.
CCK and leptin are anorectic hormones produced in the small intestine and white adipose tissue, respectively. Investigating how these hormones act together as an integrated anorectic signal is important for elucidating the mechanisms by which energy balance is maintained. We found here that coadministration of subthreshold CCK and leptin, which individually have no effect on feeding, dramatically reduced food intake in rats. Phosphorylation of AMP-activated protein kinase (AMPK) in the hypothalamus significantly decreased after coinjection of CCK and leptin. In addition, coadministration of these hormones significantly increased mRNA levels of anorectic cocaine- and amphetamine-regulated transcript (CART) and TRH in the hypothalamus. The interactive effect of CCK and leptin on food intake was abolished by intracerebroventricular preadministration of the AMPK activator AICAR or anti-CART/anti-TRH antibodies. These findings indicate that coinjection of CCK and leptin reduces food intake via reduced AMPK phosphorylation and increased CART/TRH in the hypothalamus. Furthermore, by using midbrain-transected rats, we investigated the role of the neural pathway from the hindbrain to the hypothalamus in the interaction of CCK and leptin to reduce food intake. Food-intake reduction induced by coinjection of CCK and leptin was blocked in midbrain-transected rats. Therefore, the neural pathway from hindbrain to hypothalamus plays an important role in transmitting the anorectic signals provided by coinjection of CCK and leptin. Our findings give further insight into the mechanisms of feeding and energy balance.
Adipose tissue is a complex organ that comprises a wide range of cell types with diverse energy storage, metabolic regulation, and neuroendocrine and immune functions. Because it contains various immune cells, either adaptive (B and T lymphocytes; such as regulatory T cells) or innate (mostly macrophages and, more recently identified, myeloid-derived suppressor cells), the adipose tissue is now considered as a bona fide immune organ, at the cross-road between metabolism and immunity. Adipose tissue disorders, such as those encountered in obesity and lipodystrophy, cause alterations to adipose tissue distribution and function with broad effects on cytokine, chemokine, and hormone expression, on lipid storage, and on the composition of adipose-resident immune cell populations. The resulting changes appear to induce profound consequences for basal systemic inflammation and insulin sensitivity. The purpose of this review is to synthesize the current literature on adipose cell composition remodeling in obesity, which shows how adipose-resident immune cells regulate inflammation and insulin resistance-notably through cytokine and chemokine secretion-and highlights major research questions in the field.
Monocyte chemoattractant protein-1 (MCP-1), an important chemokine whose expression is increased during the course of obesity, plays a role in macrophage infiltration into obese adipose tissue. This study was designed to elucidate the role of mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) in the induction of MCP-1 during the course of adipocyte hypertrophy. We examined the time course of MKP-1 and MCP-1 mRNA expression and extracellular signal-regulated kinase (ERK) phosphorylation in the adipose tissue from mice rendered mildly obese by a short term high fat diet. We also studied the role of MKP-1 in the induction of MCP-1 in 3T3-L1 adipocytes during the course of adipocyte hypertrophy. MCP-1 mRNA expression was increased, followed by ERK activation and down-regulation of MKP-1, an inducible dual specificity phosphatase to inactivate ERK, in the adipose tissue at the early stage of obesity induced by a short term high fat diet, when macrophages are not infiltrated. Down-regulation of MKP-1 preceded ERK activation and increased production of MCP-1 in 3T3-L1 adipocytes in vitro during the course of adipocyte hypertrophy. Adenovirus-mediated restoration of MKP-1 in hypertrophied 3T3-L1 adipocytes reduced the otherwise increased ERK phosphorylation, thereby leading to the significant reduction of MCP-1 mRNA expression. This study provides evidence that the down-regulation of MKP-1 is critical for increased production of MCP-1 during the course of adipocyte hypertrophy.
OBJECTIVE
Human blood glucose levels have likely evolved toward their current point of stability over hundreds of thousands of years. The robust population stability of this trait is called canalization. It has been represented by a hyperbolic function of two variables: insulin sensitivity and insulin response. Environmental changes due to global migration may have pushed some human subpopulations to different points of stability. We hypothesized that there may be ethnic differences in the optimal states in the relationship between insulin sensitivity and insulin response.
RESEARCH DESIGN AND METHODS
We identified studies that measured the insulin sensitivity index (SI) and acute insulin response to glucose (AIRg) in three major ethnic groups: Africans, Caucasians, and East Asians. We identified 74 study cohorts comprising 3,813 individuals (19 African cohorts, 31 Caucasian, and 24 East Asian). We calculated the hyperbolic relationship using the mean values of SI and AIRg in the healthy cohorts with normal glucose tolerance.
RESULTS
We found that Caucasian subpopulations were located around the middle point of the hyperbola, while African and East Asian subpopulations are located around unstable extreme points, where a small change in one variable is associated with a large nonlinear change in the other variable.
CONCLUSIONS
Our findings suggest that the genetic background of Africans and East Asians makes them more and differentially susceptible to diabetes than Caucasians. This ethnic stratification could be implicated in the different natural courses of diabetes onset.
There is an epidemic of diabetes in Asia. Type 2 diabetes develops in East Asian patients at a lower mean body mass index (BMI) compared with those of European descent. At any given BMI, East Asians have a greater amount of body fat and a tendency to visceral adiposity. In Asian patients, diabetes develops at a younger age and is characterized by early β cell dysfunction in the setting of insulin resistance, with many requiring early insulin treatment. The increasing proportion of young-onset and childhood type 2 diabetes is posing a particular threat, with these patients being at increased risk of developing diabetic complications. East Asian patients with type 2 diabetes have a higher risk of developing renal complications than Europeans and, with regard to cardiovascular complications, a predisposition for developing strokes. In addition to cardiovascular-renal disease, cancer is emerging as the other main cause of mortality. While more research is needed to explain these interethnic differences, urgent and concerted actions are needed to raise awareness, facilitate early diagnosis, and encourage preventive strategies to combat these growing disease burdens.
The sympathetic nervous system (SNS) is known to play a pivotal role in short- and long-term regulation of different functions of the cardiovascular system. In the past decades increasing evidence demonstrated that sympathetic neural control is involved not only in the vasomotor control of small resistance arteries but also in modulation of large artery function. Sympathetic activity and vascular function, both of which are key factors in the development and prognosis of cardiovascular events and disease, are linked at several levels. Evidence from experimental studies indicates that the SNS is critically influenced, at the central and also at the peripheral level, by the most relevant factors regulating vascular function, such as nitric oxide (NO), reactive oxygen species (ROS), endothelin (ET), the renin-angiotensin system. Additionally, there is indirect evidence of a reciprocal relationship between endothelial function and activity of the SNS. A number of cardiovascular risk factors and diseases are characterized both by increased sympathetic outflow and decreased endothelial function. In healthy subjects, muscle sympathetic nerve activity (MSNA) appears to be related to surrogate markers of endothelial function, and an acute increase in sympathetic activity has been associated with a decrease in endothelial function in healthy subjects. However, direct evidence of a cause-effect relationship from human studies is scanty. In humans large artery stiffness has been associated with increased sympathetic discharge, both in healthy subjects and in renal transplant recipients. Peripheral sympathetic discharge is also able to modulate wave reflection. On the other hand, large artery stiffness can interfere with autonomic regulation by impairing carotid baroreflex sensitivity.
Stressful stimuli evoke complex endocrine, autonomic, and behavioral responses that are extremely variable and specific depending on the type and nature of the stressors. We first provide a short overview of physiology, biochemistry, and molecular genetics of sympatho-adrenomedullary, sympatho-neural, and brain catecholaminergic systems. Important processes of catecholamine biosynthesis, storage, release, secretion, uptake, reuptake, degradation, and transporters in acutely or chronically stressed organisms are described. We emphasize the structural variability of catecholamine systems and the molecular genetics of enzymes involved in biosynthesis and degradation of catecholamines and transporters. Characterization of enzyme gene promoters, transcriptional and posttranscriptional mechanisms, transcription factors, gene expression and protein translation, as well as different phases of stress-activated transcription and quantitative determination of mRNA levels in stressed organisms are discussed. Data from catecholamine enzyme gene knockout mice are shown. Interaction of catecholaminergic systems with other neurotransmitter and hormonal systems are discussed. We describe the effects of homotypic and heterotypic stressors, adaptation and maladaptation of the organism, and the specificity of stressors (physical, emotional, metabolic, etc.) on activation of catecholaminergic systems at all levels from plasma catecholamines to gene expression of catecholamine enzymes. We also discuss cross-adaptation and the effect of novel heterotypic stressors on organisms adapted to long-term monotypic stressors. The extra-adrenal nonneuronal adrenergic system is described. Stress-related central neuronal regulatory circuits and central organization of responses to various stressors are presented with selected examples of regulatory molecular mechanisms. Data summarized here indicate that catecholaminergic systems are activated in different ways following exposure to distinct stressful stimuli.
To examine whether eating until full or eating quickly or combinations of these eating behaviours are associated with being overweight. Design and participants Cross sectional survey.
Two communities in Japan.
3287 adults (1122 men, 2165 women) aged 30-69 who participated in surveys on cardiovascular risk from 2003 to 2006.
Body mass index (overweight >/=25.0) and the dietary habits of eating until full (lifestyle questionnaire) and speed of eating (validated brief self administered questionnaire).
571 (50.9%) men and 1265 (58.4%) women self reported eating until full, and 523 (45.6%) men and 785 (36.3%) women self reported eating quickly. For both sexes the highest age adjusted mean values for height, weight, body mass index, and total energy intake were in the eating until full and eating quickly group compared with the not eating until full and not eating quickly group. The multivariable adjusted odds ratio of being overweight for eating until full was 2.00 (95% confidence interval 1.53 to 2.62) for men and 1.92 (1.53 to 2.40) for women and for eating quickly was 1.84 (1.42 to 2.38) for men and 2.09 (1.69 to 2.59) for women. The multivariable odds ratio of being overweight with both eating behaviours compared with neither was 3.13 (2.20 to 4.45) for men and 3.21 (2.41 to 4.29) for women.
Eating until full and eating quickly are associated with being overweight in Japanese men and women, and these eating behaviours combined may have a substantial impact on being overweight.
Phorbol ester tumor promoters, such as phorbol 12-myristate 13-acetate (PMA), are potent activators of extracellular signal-regulated kinase 2 (ERK2), stress-activated protein kinase (SAPK), and p38 mitogen-activated protein kinase (MAPK) in U937 human leukemic cells. These kinases are regulated by the reversible dual phosphorylation of conserved threonine and tyrosine residues. The dual specificity protein phosphatase MAPK phosphatase-1 (MKP-1) has been shown to dephosphorylate and inactivate ERK2, SAPK, and p38 MAPK in transient transfection studies. Here we demonstrate that PMA treatment induces MKP-1 protein expression in U937 cells, which is detectable within 30 min with maximal levels attained after 4 h. This time course coincides with the rapid inactivation of PMA-induced SAPK activity, but not ERK2 phosphorylation, which remains elevated for up to 6 h. To examine directly the role of MKP-1 in the regulation of these protein kinases in vivo, we established a U937 cell line that conditionally expresses MKP-1 from the human metallothionein IIa promoter. Conditional expression of MKP-1 inhibited PMA-induced ERK2, SAPK, and p38 MAPK activity. By titrating the levels of MKP-1 expression from the human metallothionein IIa promoter, however, it was found that p38 MAPK and SAPK were much more sensitive to inhibition by MKP-1 than ERK2. This differential substrate specificity of MKP-1 can be functionally extended to nuclear transcriptional events in that PMA-induced c-Jun transcriptional activity was more sensitive to inhibition by MKP-1 than either Elk-1 or c-Myc. Conditional expression of MKP-1 also abolished the induction of endogenous MKP-1 protein expression in response to PMA treatment. This negative feedback regulatory mechanism is likely due to MKP-1-mediated inhibition of ERK2, as studies utilizing the MEK1/2 inhibitor PD98059 suggest that ERK2 activation is required for PMA-induced MKP-1 expression. These findings suggest that ERK2-mediated induction of MKP-1 may play an important role in preferentially attenuating signaling through the p38 MAPK and SAPK signal transduction pathways.
New information regarding neuronal circuits that control food intake and their hormonal regulation has extended our understanding of energy homeostasis, the process whereby energy intake is matched to energy expenditure over time. The profound obesity that results in rodents (and in the rare human case as well) from mutation of key signalling molecules involved in this regulatory system highlights its importance to human health. Although each new signalling pathway discovered in the hypothalamus is a potential target for drug development in the treatment of obesity, the growing number of such signalling molecules indicates that food intake is controlled by a highly complex process. To better understand how energy homeostasis can be achieved, we describe a model that delineates the roles of individual hormonal and neuropeptide signalling pathways in the control of food intake and the means by which obesity can arise from inherited or acquired defects in their function.
Entrapment and oxidation of low density lipoproteins (LDL) in the sub-endothelial space is a key process in the initiation of atherosclerotic lesion development. Functional changes induced by oxidized lipids in endothelial cells are early events in the pathogenesis of atherosclerosis. Oxidized-l-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (ox-PAPC), a major component of minimally modified/oxidized-LDL (MM-LDL) mimics the biological activities assigned to MM-LDL both in vitro in a co-culture model as well as in vivo in mice. We hypothesized that ox-PAPC initiates gene expression changes in endothelial cells that result in enhanced endothelial/monocyte interactions. To analyze the gene expression changes that oxidized lipids induce in endothelial cells, we used a suppression subtractive hybridization procedure to compare mRNA from PAPC-treated human aortic endothelial cells (HAEC) with that of ox-PAPC-treated cells. We report here the identification of a gene, mitogen-activated protein kinase phosphatase 1 (MKP-1), that is rapidly and transiently induced in ox-PAPC-treated HAEC. Inhibition of MKP-1 using either the phosphatase inhibitor sodium orthovanadate or antisense oligonucleotides prevents the accumulation of monocyte chemotactic activity in ox-PAPC-treated HAEC supernatants. Furthermore, we show that decreased monocyte chemotactic activity in HAEC treated with sodium orthovanadate or MKP-1 antisense oligonucleotides is due to decreased MCP-1 protein. Our results implicate a direct role for MKP-1 in ox-PAPC-induced signaling pathways that result in the production of MCP-1 protein by ox-PAPC-treated HAEC.
This study identifies monocyte chemoattractant protein 1 (MCP-1) as an insulin-responsive gene. It also shows that insulin induces substantial expression and secretion of MCP-1 both in vitro in insulin-resistant (IR) 3T3-L1 adipocytes and in vivo in IR obese mice (ob/ob). Thus, MCP-1 resembles other previously described genes (e.g., PAI-1 and SREBP-1c) that remain sensitive to insulin in IR states. The hyperinsulinemia that frequently accompanies obesity and insulin resistance may therefore contribute to the altered expression of these and other genes in insulin target tissues. In vivo studies also demonstrate that MCP-1 is overexpressed in obese mice compared with their lean controls, and that white adipose tissue is a major source of MCP-1. The elevated MCP-1 may alter adipocyte function because addition of MCP-1 to differentiated adipocytes in vitro decreases insulin-stimulated glucose uptake and the expression of several adipogenic genes (LpL, adipsin, GLUT-4, aP2, beta3-adrenergic receptor, and peroxisome proliferator-activated receptor gamma). These results suggest that elevated MCP-1 may induce adipocyte dedifferentiation and contribute to pathologies associated with hyperinsulinemia and obesity, including type II diabetes.
Obesity is associated with a state of chronic, low-grade inflammation. Two manuscripts in this issue of the JCI (see the related articles beginning on pages 1796 and 1821) now report that obese adipose tissue is characterized by macrophage infiltration and that these macrophages are an important source of inflammation in this tissue. These studies prompt consideration of new models to include a major role for macrophages in the molecular changes that occur in adipose tissue in obesity.
To review the evidence on the diet and nutrition causes of obesity and to recommend strategies to reduce obesity prevalence.
The evidence for potential aetiological factors and strategies to reduce obesity prevalence was reviewed, and recommendations for public health action, population nutrition goals and further research were made.
Protective factors against obesity were considered to be: regular physical activity (convincing); a high intake of dietary non-starch polysaccharides (NSP)/fibre (convincing); supportive home and school environments for children (probable); and breastfeeding (probable). Risk factors for obesity were considered to be sedentary lifestyles (convincing); a high intake of energy-dense, micronutrient-poor foods (convincing); heavy marketing of energy-dense foods and fast food outlets (probable); sugar-sweetened soft drinks and fruit juices (probable); adverse social and economic conditions-developed countries, especially in women (probable). A broad range of strategies were recommended to reduce obesity prevalence including: influencing the food supply to make healthy choices easier; reducing the marketing of energy dense foods and beverages to children; influencing urban environments and transport systems to promote physical activity; developing community-wide programmes in multiple settings; increased communications about healthy eating and physical activity; and improved health services to promote breastfeeding and manage currently overweight or obese people.
The increasing prevalence of obesity is a major health threat in both low- and high income countries. Comprehensive programmes will be needed to turn the epidemic around.
The prevalence of overweight and obesity has increased markedly in the last 2 decades in the United States.
To update the US prevalence estimates of overweight in children and obesity in adults, using the most recent national data of height and weight measurements.
As part of the National Health and Nutrition Examination Survey (NHANES), a complex multistage probability sample of the US noninstitutionalized civilian population, both height and weight measurements were obtained from 4115 adults and 4018 children in 1999-2000 and from 4390 adults and 4258 children in 2001-2002.
Prevalence of overweight (body mass index [BMI] > or =95th percentile of the sex-specific BMI-for-age growth chart) among children and prevalence of overweight (BMI, 25.0-29.9), obesity (BMI > or =30.0), and extreme obesity (BMI > or =40.0) among adults by sex, age, and racial/ethnic group.
Between 1999-2000 and 2001-2002, there were no significant changes among adults in the prevalence of overweight or obesity (64.5% vs 65.7%), obesity (30.5% vs 30.6%), or extreme obesity (4.7% vs 5.1%), or among children aged 6 through 19 years in the prevalence of at risk for overweight or overweight (29.9% vs 31.5%) or overweight (15.0% vs 16.5%). Overall, among adults aged at least 20 years in 1999-2002, 65.1% were overweight or obese, 30.4% were obese, and 4.9% were extremely obese. Among children aged 6 through 19 years in 1999-2002, 31.0% were at risk for overweight or overweight and 16.0% were overweight. The NHANES results indicate continuing disparities by sex and between racial/ethnic groups in the prevalence of overweight and obesity.
There is no indication that the prevalence of obesity among adults and overweight among children is decreasing. The high levels of overweight among children and obesity among adults remain a major public health concern.
Dietary factors such as taste and nutrients are known to affect satiety and energy balance. We hypothesized that food texture might contribute to the regulation of energy metabolism through the process of mastication in the oral cavity as well. The effects of long-term feeding of different-textured pellets on body weight gain, adiposity, and thermogenesis were assessed. From weaning at 4 wks, rats were divided into 2 groups fed on either standard (controls) or soft pellets (soft-fed) that required less chewing with the same nutritional composition. At 26 wks, the soft-fed rats showed greater adiposity than did the controls. Daily food intake did not differ between the 2 groups. The increase in body temperature following feeding was significantly lower in the soft-fed rats. These results suggested that food texture affected energy metabolism by changing post-prandial thermogenesis. The long-term deficiency of thermogenesis associated with soft foods resulted in a greater tendency toward obesity.
Few epidemiologic studies have examined the association between the rate of eating and obesity. In this study, we cross-sectionally examined the association of the self-reported rate of eating with current Body Mass Index (BMI), and BMI-change from 20 years of age to the current age.
Subjects were 3737 male (mean age +/- standard deviation and mean BMI +/- standard deviation: 48.2 +/- 7.1 years and 23.3 +/- 2.7 kg/m(2)) and 1005 female (46.3 +/- 7.0 years and 21.8 +/- 2.8 kg/m(2)) Japanese civil servants. We measured self-reported categorical rate of eating, current BMI, BMI at age 20, and BMI-change from age 20. Energy intake was assessed over a 1-month period with a brief-type diet history questionnaire.
The multiple regression analysis in which the current BMI was regressed by categorical rate of eating, energy intake, age, and lifestyle factors showed that current BMI steadily increased by -0.99, -0.67, 0.81, and 1.47 kg/m(2) along with the progress of categorical rate of eating from the 'medium' group to 'very slow', 'relatively slow', 'relatively fast', and 'very fast' groups, respectively, in men. In women, the corresponding values were -1.06, -0.35, 0.50, and 1.34 kg/m(2). When the BMI increment from age 20 to current age was regressed in the same manner, the increment was -0.63, -0.34, 0.57, and 1.05 kg/m(2) in men and -0.71, -0.32, 0.34, and 1.14 kg/m(2) in women, respectively. Additionally, both BMI at age 20 and current height were positively associated with rate of eating.
Our results among middle-aged men and women suggest that eating fast would lead to obesity.
The capacity to adjust food intake in response to changing energy requirements is essential for survival. Recent progress has provided an insight into the molecular, cellular and behavioural mechanisms that link changes of body fat stores to adaptive adjustments of feeding behaviour. The physiological importance of this homeostatic control system is highlighted by the severe obesity that results from dysfunction of any of several of its key components. This new information provides a biological context within which to consider the global obesity epidemic and identifies numerous potential avenues for therapeutic intervention and future research.
The prevalence of type 2 diabetes in adolescents and young adults is dramatically increasing. Similar to older-onset type 2 diabetes, the major predisposing risk factors are obesity, family history, and sedentary lifestyle. Onset of diabetes at a younger age (defined here as up to age 40 years) is associated with longer disease exposure and increased risk for chronic complications. Young-onset type 2 diabetes also affects more individuals of working age, accentuating the adverse societal effects of the disease. Furthermore, evidence is accumulating that young-onset type 2 diabetes has a more aggressive disease phenotype, leading to premature development of complications, with adverse effects on quality of life and unfavourable effects on long-term outcomes, raising the possibility of a future public health catastrophe. In this Review, we describe the epidemiology and existing knowledge regarding pathophysiology, risk factors, complications, and management of type 2 diabetes in adolescents and young adults.
Cancer cells often have characteristic changes in metabolism. Cellular proliferation, a common feature of all cancers, requires fatty acids for synthesis of membranes and signaling molecules. Here, we provide a view of cancer cell metabolism from a lipid perspective, and we summarize evidence that limiting fatty acid availability can control cancer cell proliferation.
Regulation of body weight is organized by distributed brain circuits that use a variety of neuropeptides and transmitters, and that are responsive to endocrine and metabolic signals. Targeting of these circuits with novel pharmaceutical drugs would be helpful additions to lifestyle interventions for the treatment of obesity. The recent FDA approval of two anti-obesity drugs holds promise in a field in which previous drugs were removed from clinical use because of unacceptable psychiatric and cardiovascular side effects. Here, the modes of action of anti-obesity drugs are reviewed.
To determine whether adults diagnosed with type 2 diabetes from age 18 to 44 years more aggressively develop clinical complications after diagnosis than adults diagnosed at >or=45 years of age.
We compared outcomes among 7844 adults in a health maintenance organization who were newly diagnosed with type 2 diabetes between 1996 and 1998. We abstracted clinical data from electronic medical, laboratory, and pharmacy records. To adjust for length of follow-up and sex, we used proportional hazards models to compare incident complication rates through 2001 between onset groups (mean follow-up 3.9 years). To adjust for the increasing prevalence of macrovascular disease with advancing age, onset groups were matched by age and sex to control subjects without diabetes for macrovascular outcomes.
Adults with early-onset type 2 diabetes were 80% more likely to begin insulin therapy than those with usual-onset type 2 diabetes (hazards ratio [HR] 1.8, 95% CI 1.5-2.0), despite a similar average time to requiring insulin ( approximately 2.2 years). Although the combined risk of microvascular complications did not differ overall, microalbuminuria was more likely in early-onset type 2 diabetes than usual-onset type 2 diabetes (HR 1.2, 95% CI 1.1-1.4). The hazard of any macrovascular complication in early-onset type 2 diabetic patients compared with control subjects was twice as high in usual-onset type 2 diabetic patients compared with control subjects (HR 7.9 vs. 3.8, respectively). Myocardial infarction (MI) was the most common macrovascular complication, and the hazard of developing an MI in early-onset type 2 diabetic patients was 14-fold higher than in control subjects (HR 14.0, 95% CI 6.2-31.4). In contrast, adults with usual-onset type 2 diabetes had less than four times the risk of developing an MI compared with control subjects (HR 3.7, P < 0.001).
Early-onset type 2 diabetes appears to be a more aggressive disease from a cardiovascular standpoint. Although the absolute rate of cardiovascular disease (CVD) is higher in older adults, young adults with early-onset type 2 diabetes have a much higher risk of CVD relative to age-matched control subjects.
The discovery that the brain contains neurons utilizing dopamine (DA) as their transmitter has led to studies of the behavioral function of these neurons. Changes in overall level of activity of DA neurons appear to produce parallel changes in locomotor activity. Additionally, DA neurons seem to mediate in part the effects of biologically significant (reinforcing) stimuli on learning. One way in which reinforcing stimuli produce learning is to increase the incentive motivational (response-eliciting) properties of neutral stimuli associated with them; also, reinforcing stimuli maintain the incentive motivational properties of previously conditioned incentive stimuli. Normal DA functioning appears to be required for the establishment and maintenance of incentive learning in naive animals. Previous incentive learning in trained animals can influence behavior for a time even when the function of DA neurons is disrupted; however, with continued testing in the absence of normal DA functioning, previously established conditioned incentive stimuli cease to influence behavior. From these observations and recent physiological, anatomical and biochemical studies of DA systems it is suggested that the biological substrate of DA-mediated incentive learning is a heterosynaptic facilitation of muscarinic cholinergic synapses. This model has important clinical implications since it has been suggested that DA hyperfunctioning underlies the development of schizophrenia.
Early childhood overweight and obesity have alarmingly increased over the years. Adulthood obesity is a well demonstrated significant independent predictor of cardiovascular risk (CVR) and/or mortality, which predisposes to the major components of metabolic syndrome (MS). Evidence of MS in obese children has been also reported associated with biochemical and inflammatory factors that affect vascular physiologic function. Assessment of vascular function can be measured noninvasively in children allowing early detection of endothelial dysfunction and severe increase of arterial stiffness before clinical manifestations of atherosclerosis. Impairment of endothelial function related to the severity of obesity and to the degree of insulin resistance is considered as a condition that confers a premature atherogenicity status and is linked to adult conventional cardiovascular risk factors. Adipose tissue factors that interfere with insulin action and endothelial cell function have also been identified as major precursors of CVR factors. The metabolic and cardiovascular consequences of childhood obesity are well demonstrated and have a major impact on the development of atherosclerosis and lifetime CVR. The development of programs involving both diet and exercise for children with overt overweight/obesity appears to be essential to improve vascular function and metabolic disorders. Such interventions should be complemented by a primary prevention against childhood obesity.
UV irradiation induces apoptosis in U937 human leukemic cells that is accompanied by the activation of both the stress-activated protein kinase (SAPK) and p38 mitogen-activated protein kinase (MAPK) signal transduction pathways. The MAPK phosphatase, MKP-1, is capable of inactivating both SAPK and p38 MAPK in vivo. To determine whether MKP-1-mediated inhibition of SAPK and/or p38 MAPK activity provided cytoprotection against UV-induced apoptosis, a U937 cell line conditionally expressing MKP-1 from the human metallothionein IIa promoter was established. Conditional expression of MKP-1 was found to abolish UV-induced SAPK and p38 MAPK activity, and inhibit UV-induced apoptosis as judged by both morphological criteria and DNA fragmentation. MKP-1 was also found to inhibit other biochemical events associated with apoptosis, including activation of caspase-3 and the proteolytic cleavage of the caspase-3 substrate, poly(ADP ribose) polymerase. These findings demonstrate that MKP-1 acts at a site upstream of caspase activation within the apoptotic program. The cytoprotective properties of MKP-1 do not appear to be mediated by its ability to inhibit p38 MAPK because the p38 MAPK specific inhibitor SB203580 had no effect on UV-induced apoptosis in U937 cells. Furthermore, by titrating the level of MKP-1 expression it was found that MKP-1 inhibited UV-induced SAPK activity, DNA fragmentation, and caspase-3 activation in a similar dose-dependent manner. The dual-specificity phosphatase, PAC1, which does not inhibit UV-induced activation of SAPK, did not provide a similar cytoprotection against UV-induced apoptosis. These results are consistent with a model whereby MKP-1 provides cytoprotection against UV-induced apoptosis by inhibiting UV-induced SAPK activity.
To examine the satiety effect of carbohydrates with a focus on the comparison of liquid and solid food and their implications for energy balance and weight management.
A number of studies have examined the role of dietary fiber, whole grains, and glycemic index or glycemic load on satiety and subsequent energy intake, but results remain inconclusive. Intake of liquid carbohydrates, particularly sugar-sweetened beverages, has increased considerably across the globe in recent decades in both adolescents and adults. In general, liquid carbohydrates produce less satiety compared with solid carbohydrates. Some energy from liquids may be compensated for at subsequent meals but because the compensation is incomplete, it leads to an increase in total long-term energy intake. Recent studies also suggest some potential differential responses of satiety by characteristics of the patients (e.g., race, sex, and body weight status). These differences warrant further research.
Satiety is a complex process influenced by a number of properties in food. The physical form (solid vs. liquid) of carbohydrates is an important component that may affect the satiety process and energy intake. Accumulating evidence suggests that liquid carbohydrates generally produce less satiety than solid forms.
Both the metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM) confer an increased risk of coronary heart disease and cardiovascular disease (CVD). As MS and T2DM become more prevalent, there will be an associated rise in the number of individuals with or at risk for CVD and its related disorders. One major underlying cause of CVD in patients with MS or T2DM is a characteristic form of atherogenic dyslipidemia. This article reviews the evidence that demonstrates that individuals with MS or T2DM are at increased risk for CVD and highlights atherogenic dyslipidemia as an important risk factor for the development of CVD in these individuals. In an accompanying article, current pharmacotherapies available for the management of atherogenic dyslipidemia in individuals with MS or T2DM are discussed.
To study the possible participation of food-induced sensory stimulation on meal thermogenesis an experiment was performed with eight female subjects. On alternate days subjects were fed either a highly palatable meal (HPM), containing 710 calories, or a nonpalatable meal (NPM). The NPM was prepared by mixing all the ingredients of the HPM and was presented to the subjects as a desiccated biscuit. The subjects were not informed about the composition of the NPM, which they rated as tasteless and unappetizing. The increase in O2 consumption was approximately 20% during the 90 min following the HPM compared with 12% with the NPM (P less than 0.01). With comparable increases in plasma glucose, plasma insulin level was significantly (P less than 0.01) lower following NPM ingestion than with ingestion of the HPM. At that time a significant increase in plasma norepinephrine was also observed but only following ingestion of the HPM. It would appear that both central sensory stimulation or plasma insulin level, as affected by food palatability, could be considered at this time as possible activators of the increased sympathetic activity observed following ingestion of the HPM. It is suggested that a part of meal thermogenesis is due to food palatability and that the concomitant activation of the sympathetic system may be related to this action.
Tumor necrosis factor-alpha (TNF-alpha) has been shown to have certain catabolic effects on fat cells and whole animals. An
induction of TNF-alpha messenger RNA expression was observed in adipose tissue from four different rodent models of obesity
and diabetes. TNF-alpha protein was also elevated locally and systemically. Neutralization of TNF-alpha in obese fa/fa rats
caused a significant increase in the peripheral uptake of glucose in response to insulin. These results indicate a role for
TNF-alpha in obesity and particularly in the insulin resistance and diabetes that often accompany obesity.
Spontaneous locomotor activity in diabetic mice was significantly greater than that in non-diabetic mice. Haloperidol and SCH23390, a selective dopamine D1-receptor antagonist, significantly reduced spontaneous locomotor activity in diabetic mice, but not in non-diabetic mice. Spontaneous locomotor activity in diabetic mice was also reduced by pretreatment with naltrindole, a selective delta-opioid receptor antagonist, and 7-benzylidenenaltrexone, a selective delta1-opioid receptor antagonist. The rate of dopamine turnover in the limbic forebrain in diabetic mice was significantly higher than that in non-diabetic mice. These findings suggest that the enhanced spontaneous locomotor activity in diabetic mice may result from increased dopamine neurotransmission, which might be due to an increase in dopamine release in mesolimbic dopamine systems. The increased dopamine neurotransmission in diabetic mice may also be due to the up-regulation of delta-opioid receptor-mediated functions.
The effect of bite size on ingestion rate, satiation, and meal size was studied in nine lean and nine obese women. On separate days, subjects were given one of three bite sizes of sandwiches and one of two bite sizes of bagels with cream cheese to eat in a laboratory lunch. Decreasing bite size significantly lowered ingestion rate for the whole meal. The effect was most pronounced at the beginning of meals. As bite size decreased from 15 to 5 g, the average ingestion rate decreased from (mean +/- SEM) 19.4 +/- 2.0 to 15.9 +/- 2.0 g/min (p < 0.001). The initial ingestion rate decreased from 30.0 +/- 2.9 to 19.6 +/- 1.7 g/min (p < 0.001). The larger the bite size, the more quickly ingestion rate decelerated; by the end of meals, ingestion rate was not different across conditions. The decrease in ingestion rate with smaller bites was offset by an increase in meal duration, such that meal size did not differ across conditions. Eating behavior of lean and obese subjects was not different. There were individual differences related to ingestion rate, but these were not related to body weight nor to meal size. These results bring into question the recommendation of behavior therapists that obese people eat more slowly in order to eat less.
We investigated whether enhanced spontaneous locomotor activity in streptozotocin (STZ)-induced diabetic mice is associated with serum glucose levels. Furthermore, the role of factor(s) derived from spleen cells on the enhanced spontaneous locomotor activity in diabetic mice was also examined. Serum glucose levels were significantly increased on day 4 after STZ administration and remained increased at 7, 14, 28 and 56 days after STZ administration. A significant increase in spontaneous locomotor activity in diabetic mice as compared to that in non-diabetic mice was observed 4, 7, 14 or 28 days after STZ treatment. The increase in spontaneous locomotor activity in diabetic mice was not observed when insulin was chronically administered to mice 3 to 7 days after administration of STZ. Splenectomized diabetic mice, which were operated upon 7 days after STZ administration, still had a significantly higher spontaneous locomotor activity than non-diabetic mice. In contrast, spontaneous locomotor activity in diabetic mice that were splenectomized either before or 3 days after administration of STZ returned to the levels in non-diabetic mice. The rate of dopamine (DA) turnover in the limbic forebrain of diabetic mice on day 14 was significantly higher than that in age-matched non-diabetic. Although the rate of DA turnover in the diabetic mice that were splenectomized 7 days after STZ administration was significantly higher than that in non-diabetic mice, an increased the rate of DA turnover was not observed when mice were splenectomized either before or 3 days after administration of STZ. These results suggest that the lasting hyperglycemia may be responsible for their hyperlocomotion in diabetic mice within 14 days sfter STZ treatment, perhaps due to an increase in dopamine release in mesolimbic dopamine systems. Furthermore, factor(s) derived from spleen cells of diabetic mice during the incipient stages of diabetes may play a role in the enhancement of dopaminergic neurotransmission.
The metabolic syndrome is characterized by a clustering of cardiovascular risk factors including type 2 diabetes mellitus, hypertension, dyslipidemia, and obesity. Elevated plasma insulin and urinary norepinephrine (noradrenaline) and reduced urinary epinephrine (adrenaline) excretion are associated with obesity in Caucasian populations. We examined the interrelationships between obesity, plasma insulin, and urinary catecholamine excretion in Chinese subjects with various components of the metabolic syndrome. A total of 577 Chinese subjects (aged 38 +/- 10 years; 68% with type 2 diabetes mellitus, hypertension, dyslipidemia, obesity, and/or albuminuria and 32% healthy subjects) were studied, all of whom had a plasma creatinine less than 150 micromol/L. The blood pressure, height, weight, waist and hip circumference, and fasting plasma glucose, insulin, lipid, and creatinine levels were measured. A 24-hour urine sample was collected for measurement of albumin and catecholamine excretion. The body mass index (BMI) and waist circumference were used as measures of general and central obesity, respectively. The insulin resistance index was estimated by the calculated product of fasting plasma insulin and glucose concentrations. Patients with an increasing number of components of the metabolic syndrome (type 2 diabetes mellitus, hypertension, dyslipidemia, obesity, and/or albuminuria) were more obese, hyperglycemic, dyslipidemic, and albuminuric and had higher blood pressure, plasma insulin, insulin resistance indices, and 24-hour urinary norepinephrine excretion but lower urinary epinephrine output (all P < .005). Increasing quintiles of BMI in the whole population or waist circumference in both sexes were associated with increasing trends for adverse lipid profiles, plasma insulin, insulin resistance indices, and urinary norepinephrine excretion but a decreasing trend for urinary epinephrine output (all P < .001). There were close associations between age, obesity, blood pressure, fasting plasma glucose, lipid, insulin, insulin resistance indices, and urinary catecholamine excretion. Using stepwise multiple regression analysis (all P < .001), 34% of the variability of the BMI and 45% of that of the waist circumference were independently related to gender (waist higher in males and BMI higher in females), increased plasma insulin, triglyceride, and urinary norepinephrine excretion, and decreased high-density lipoprotein (HDL) cholesterol and urinary epinephrine output. In Chinese subjects with different manifestations of the metabolic syndrome, hyperinsulinemia, insulin resistance, elevated norepinephrine, and reduced epinephrine excretion were closely associated with general and central obesity. Based on these findings, we postulate that complex interactions between the insulin and sympathoadrenal systems may lead to the development of obesity and the metabolic syndrome.
Accumulating evidence indicates that energy-yielding beverages evoke weaker appetitive responses than more solid food items, but the properties responsible have not been characterized. The present study attempted to isolate an influence of viscosity. At weekly intervals, 84 adults ingested 325-ml (220 kcal) shakes that were matched on weight, volume, temperature, energy, macronutrient content, energy density, rate of consumption, cognitive expectations, palatability, appearance, and requirements for mechanical processing, but varied in viscosity. Twice appetitive ratings were obtained over the subsequent 4 h, while all intake was proscribed, and twice ratings were kept until the first spontaneous eating occasion comprised of > or =100 kcal. Dietary intake was recorded over the 24 h after shake ingestion. Significantly greater and more prolonged reductions of hunger were observed with the thicker shake. No significant differences were noted in the size or time to first meal or 24 h energy intake. These data indicate viscosity exerts an independent inverse effect on hunger in humans.
Multicellular organisms have three well-characterized subfamilies of mitogen-activated protein kinases (MAPKs) that control
a vast array of physiological processes. These enzymes are regulated by a characteristic phosphorelay system in which a series
of three protein kinases phosphorylate and activate one another. The extracellular signal–regulated kinases (ERKs) function
in the control of cell division, and inhibitors of these enzymes are being explored as anticancer agents. The c-Jun amino-terminal
kinases (JNKs) are critical regulators of transcription, and JNK inhibitors may be effective in control of rheumatoid arthritis.
The p38 MAPKs are activated by inflammatory cytokines and environmental stresses and may contribute to diseases like asthma
and autoimmunity.
To examine associations between rate of eating and macronutrient and dietary fiber intake, and body mass index (BMI).
Cross-sectional study.
A total of 1695 18-y-old female Japanese dietetic students.
Macronutrient intake (protein, carbohydrate, and fat) and dietary fiber intake were assessed over a 1-month period with a validated, self-administered, diet history questionnaire. Body height and weight and rate of eating (according to five categories) were self-reported.
Among the nutrients examined, only dietary fiber intake weakly, but significantly, and negatively correlated with BMI in a multiple regression analysis. The rate of eating showed a significant and positive correlation with BMI. The mean BMI was higher by 2.2, 1.5, 1.0, and 0.5 kg/m(2) in the 'very fast', 'relatively fast', 'medium', and 'relatively slow' groups, respectively, compared with the 'very slow' rate of eating group. This correlation remained evident after adjustment for nutrient intake.
Rate of eating showed a significant and positive correlation with BMI, whereas only dietary fiber intake showed a weak correlation with BMI.
Obesity has been described as an epidemic because of the rapid increase in the number of overweight and obese individuals over the past 20 yr. This increasing prevalence of obesity is a worldwide phenomenon affecting both children and adults. The metabolic syndrome is a constellation of central adiposity, impaired fasting glucose, elevated blood pressure, and dyslipidemia (high triglyceride and low HDL cholesterol). When three of these five criteria are present, the risk of cardiovascular disease and diabetes is increased 1.5- to 2-fold. As body weight, expressed as the BMI, rises, there are a number of other diseases that are associated with it. First, life span is shortened and the risk of sudden death increases. Second, the risk of diabetes, gall bladder disease, hypertension, heart disease, osteoarthritis, sleep apnea, and certain forms of cancer also increase.
Catecholaminergic systems in stress: Structural and molecular genetic approaches
- Kvetnansky
Tumor necrosis factor alpha: A key component of the obesity-diabetes link
- G S Hotamisligil
- B M Spiegelman
Hotamisligil, G. S., & Spiegelman, B. M. (1994). Tumor necrosis factor alpha:
A key component of the obesity-diabetes link. Diabetes, 43, 1271-1278.
https://doi.org/10.2337/diab.43.11.1271
Adipose expression of tumor necrosis factor-alpha: Direct role in obesity-linked insulin resistance
- Hotamisligil
The role of dopamine in locomotor activity and learning
- Beninger R. J.
Ethnic differences in the relationship between insulin sensitivity and insulin response: A systematic review and meta-analysis
- Kodama
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