Abdominal White Adipose Tissue Research Articles

Energy metabolism during chronic REM sleep deprivation: the start of something big

In rodent models of chronic and unremitting sleep deprivation, hyperphagia develops after 5‐6 days. If the regimen is taken to 10‐20 days, food intake increases substantially irrespective of whether rats are fed chow or a palatable calorie‐dense liquid diet (Ensure); body weight does not increase. Moreover, in a new model of chronic sleep restriction, sleep deprivation is enforced for 20 hours followed by 4 hours of recovery in home cages, and this also leads to hyperphagia. Of importance is that despite greatly increased food intake in all paradigms, rats consistently fail to gain body weight. This can only happen if there is an increase in energy metabolism. Indeed, the resting metabolic rate of sleep‐deprived rats becomes elevated, mediated by robust up‐regulation of uncoupling protein 1 in brown adipose tissue. Additionally, gene expression of uncoupling protein 3 in skeletal muscle is strongly stimulated, although the role of this protein in thermogenesis remains controversial. Chronically sleep‐deprived rats show rapid mobilization of hepatic and muscle glycogen, followed by reduction in abdominal white adipose tissue. Despite a lack of weight gain, there is evidence to suggest that sleep deprivation/restriction leads to glucose dysregulation. For example, sleep‐deprived rats have a higher glucose:insulin ratio, and when challenged with an intraperitoneal glucose tolerance test, blood glucose of sleep‐restricted rats is higher than in controls. In summary, rat models of sleep deprivation/restriction may be useful tools in understanding the etiology of hyperphagia and suggest a dissociation between weight gain and glucose dysregulation and insulin resistance.Supported by NCRR RCMI and a Pilot and Feasibility grant from the Clinical Nutrition Research Unit of Maryland, P30DK072488.

Consumption of Cranberry Reduces Weight Gain in Mice Fed High Fat Diets

Obesity and dyslipidemia are major risk factors for cardiovascular disease. To test the health effects of antioxidant‐enriched diets, high‐fat diets (20% by weight) were fed to control (C57BL/6J) and apolipoprotein E‐deficient (ApoE‐/‐) mice, a strain that develops atherosclerotic lesions. Mice were fed either normal AIN‐93 purified diet (CON) or one that contained 5% freeze‐dried cranberry (Vaccinium macrocarpon; CB) for 8 weeks. There was less weight gain in animals fed CB from weeks 3 through 8 (p<0.05; two‐way ANOVA). At week 8, control mice fed CON weighed 39.4 ± 1.95 g, compared to 35.4 ± 1.55 g for control mice fed CB. Similarly, at week 8, ApoE‐/‐ mice fed CON weighed 40.5 ± 1.22 g, compared to 37.5 ± 1.60 g for those fed CB. The amount of abdominal white adipose tissue was lower in CB‐fed mice. Diets were found to be isocaloric, and there were no differences measured in the levels of carbohydrates, fats, cholesterol, and protein in the 2 diets. ApoE‐/‐ mice had elevated plasma cholesterol, HDL, and triglyceride values (p<0.0001), but diet had no effect on any of these endpoints. Plasma pyruvate, lactate, and keto acids will be measured to determine a potential metabolic mechanism for reduced weight gain. These data suggest that CB diet may improve energy balance which would benefit cardiovascular disease and obesity. (Funded by AIF and NSERC).

Catalpic acid decreases abdominal fat deposition, improves glucose homeostasis and upregulates PPAR α expression in adipose tissue

Catalpic acid (CAT) is a conjugated linolenic acid (CLN) isomer containing trans-9, trans-11, cis-13 double bonds in an 18-carbon chain and it is found primarily in the seed oil of ornamental and medicinal trees and shrubs of the family Bignoniaceae. The objective of this study was to investigate whether CAT decreases obesity and ameliorates insulin sensitivity and glucose tolerance in mice fed high-fat diets. To test the efficacy of CAT in decreasing obesity and diabetes we used both a model of diet-induced obesity (DIO) and a genetic model of obesity (i.e., mice lacking the leptin receptor). Blood was collected on days 0, 7, 14, 21 and 28 for determining fasting glucose and insulin concentrations in plasma. In addition, a glucose tolerance test was administered on day 28. We found that dietary CAT (1g/100g) decreased fasting plasma glucose and insulin concentrations, ameliorated the glucose normalizing ability following glucose challenge and decreased abdominal white adipose tissue accumulation. In white adipose tissue (WAT), CAT upregulated peroxisome proliferator-activated receptor (PPAR) alpha and its responsive genes [i.e., stearoyl-coenzyme A desaturase (SCD1) and enoyl-coenzyme A hydratase (ECH)], increased concentrations of high-density lipoprotein (HDL) cholesterol and decreased plasma triglyceride (TG) levels. CAT decreased abdominal fat deposition, increased HDL cholesterol, decreased TG concentrations, decreased glucose and insulin homeostasis and modulated WAT gene expression in a manner reminiscent of the actions of the PPAR alpha-activating fibrate class of lipid-lowering drugs.

Seaweed carotenoid, fucoxanthin, as a multi-functional nutrient.

Fucoxanthin has a unique structure including an unusual allenic bond and 5, 6-monoepoxide in its molecule. We found that abdominal white adipose tissue (WAT) weights of rats and mice fed fucoxanthin were significantly lower than those fed a control diet. The daily intake of fucoxanthin in mice also caused a significant reductions of body weight. Clear signals of uncoupling protein 1 (UCP1) and its mRNA were detected by Western and Northern blot analyses in abdominal WAT in mice fed fucoxanthin, although there is little expression of UCP1 in WAT in mice fed a control diet. UCP1 expression in WAT by fucoxanthin intake leads to oxidation of fatty acids and heat production in WAT mitochondria. Substrate oxidation can directly reduce WAT in animals. Fucoxanthin intake also significantly reduced blood glucose and plasma insulin. Furthermore, feeding fucoxanthin significantly increased the level of hepatic docosahexaenoic acid (DHA), a most important n-3 functional polyunsaturated fatty acid in biological systems. These multi-functionalities of fucoxanthin indicate that it is an important bioactive carotenoid that is beneficial for the prevention of the metabolicsyndrome.

Dietary soy and tea combinations for prevention of breast and prostate cancers by targeting metabolic syndrome elements in mice

Background: The prevalence of metabolic syndrome is high and is increasing in parallel with increasing incidences of breast and prostate cancers. The combination of soy with tea was shown to have synergistic effects on preventing breast and prostate tumors, but the effects of soy and tea combinations on metabolic syndrome–related elements have not been investigated.Objective: We aimed to determine the effects of soy and tea components, alone and in combination, on abdominal adipose mass and serum concentrations of adipokines, growth factors, and sex hormones in male and female mice.Design: Male and female FVB/N mice were treated with soy, tea components, or both. Food intake and body weight were monitored weekly. At the end of the experiment, abdominal white adipose tissue was weighed, and serum concentrations of biomarkers were measured.Results: Whole teas, but not the tea polyphenol extracts, significantly reduced abdominal white adipose tissue by 43–60% in female mice and by 65–70% in male mice. The combination of soy phytochemical concentrate and green tea reduced serum insulin-like growth factor-I concentrations in both male and female mice in a synergistic manner. The soy phytochemical concentrate and tea combinations reduced serum estrogen concentrations in female mice in a synergistic manner. Soy phytochemical concentrate and teas also significantly reduced serum leptin concentrations in both male and female mice and testosterone concentrations in male mice.Conclusion: Further research is warranted to investigate whether soy and tea combinations may prevent breast or prostate cancer in a synergistic manner in part by alleviating metabolic disorders.

Leptin requires canonical migratory signaling pathways for induction of monocyte and macrophage chemotaxis

The growing worldwide obesity epidemic is frequently linked to an increased risk of developing diseases such as diabetes, cardiovascular disease, and cancer. These diseases are associated with the infiltration of macrophages in white adipose tissue (WAT), the artery wall, and tumors, respectively; and these macrophages likely contribute to disease progression and pathogenesis. Abdominal WAT, adipose tissue surrounding the heart and artery wall, as well as carcinoma cells, secrete many factors that could induce macrophage infiltration. Leptin is an adipocyte-secreted hormone, and deficiency of either leptin or its receptor has been shown to cause morbid obesity in animals and in humans. However, what is more commonly noted in human obesity is the presence of central leptin resistance leading to hyperleptinemia. As leptin receptors are present on macrophages, we hypothesized that leptin could act as a monocyte/macrophage chemoattractant. Our current study demonstrates: 1) leptin is a potent chemoattractant for monocytes and macrophages, inducing maximal chemotactic responses at 1 ng/ml; 2) leptin-mediated chemotaxis requires the presence of full-length leptin receptors on migrating cells; 3) leptin causes increased influx of intracellular calcium in macrophages; and 4) activation of janus kinase/signal transducers and activators of transduction (JAK/STAT), mitogen-activated protein kinase (MAPK), and phosphatidylinositol 3-kinase (PI3K) pathways are all necessary for leptin-induced macrophage migration. Taken together, these data demonstrate that leptin is a potent monocyte/macrophage chemoattractant in vitro and that canonical cell motility machinery is activated upon macrophage exposure to leptin. These data have implications for the impact of hyperleptinemia on obesity-related pathophysiological conditions such as diabetes, cardiovascular disease, and cancer.

The effect of fat removal on glucose tolerance is depot specific in male and female mice

Energy is stored predominately as lipid in white adipose tissue (WAT) in distinct anatomical locations, with each site exerting different effects on key biological processes, including glucose homeostasis. To determine the relative contributions of subcutaneous and visceral WAT on glucose homeostasis, comparable amounts of adipose tissue from abdominal subcutaneous inguinal WAT (IWAT), intra-abdominal retroperitoneal WAT (RWAT), male gonadal epididymal WAT (EWAT), or female gonadal parametrial WAT (PWAT) were removed. Gonadal fat removal in both male and female chow-fed lean mice resulted in lowered glucose levels across glucose tolerance tests. Female lean C57BL/6J mice as well as male and female lean FVBN mice significantly improved glucose tolerance, indicated by decreased areas under glucose clearance curves. For the C57BL/6J mice maintained on a high-fat butter-based diet, glucose homeostasis was improved only in female mice with PWAT removal. Removal of IWAT or RWAT did not affect glucose tolerance in either dietary condition. We conclude that WAT contribution to glucose homeostasis is depot specific, with male gonadal EWAT contributing to glucose homeostasis in the lean state, whereas female gonadal PWAT contributes to glucose homeostasis in both lean and obese mice. These data illustrate both critical differences among various WAT depots and how they influence glucose homeostasis and highlight important differences between males and females in glucose regulation.

Neuropeptide Y acts directly in the periphery on fat tissue and mediates stress-induced obesity and metabolic syndrome

The relationship between stress and obesity remains elusive. In response to stress, some people lose weight, whereas others gain. Here we report that stress exaggerates diet-induced obesity through a peripheral mechanism in the abdominal white adipose tissue that is mediated by neuropeptide Y (NPY). Stressors such as exposure to cold or aggression lead to the release of NPY from sympathetic nerves, which in turn upregulates NPY and its Y2 receptors (NPY2R) in a glucocorticoid-dependent manner in the abdominal fat. This positive feedback response by NPY leads to the growth of abdominal fat. Release of NPY and activation of NPY2R stimulates fat angiogenesis, macrophage infiltration, and the proliferation and differentiation of new adipocytes, resulting in abdominal obesity and a metabolic syndrome-like condition. NPY, like stress, stimulates mouse and human fat growth, whereas pharmacological inhibition or fat-targeted knockdown of NPY2R is anti-angiogenic and anti-adipogenic, while reducing abdominal obesity and metabolic abnormalities. Thus, manipulations of NPY2R activity within fat tissue offer new ways to remodel fat and treat obesity and metabolic syndrome.

Adiponectin plays an important role in efficient energy usage under energy shortage

Adiponectin is an adipose tissue-specific secretory protein known to be an insulin-sensitizing protein. In this study, we generated adiponectin sense and antisense transgenic (Tg) mice to investigate whether adiponectin plays a role in the regulation of energy homeostasis during the growth stage. Spontaneous motor activity of antisense Tg mice were markedly reduced during fasting, particularly in young female mice, compared with wild type (Wt) and sense Tg mice. Furthermore, both body weight and adipose tissue mass of the antisense female Tg mice drastically reduced during fasting. To examine the relationship between the collapse of abdominal white adipose tissue (WAT) and serum adiponectin level, we measured the expression of genes related to energy expenditure, such as uncoupling protein (UCP). Notably, the mRNA of UCP1 in the WAT of antisense Tg female mice was markedly less than that of Wt mice and the UCP1 mRNA was strongly increased during fasting. These findings suggest that the serum adiponectin is important to maintaining energy homeostasis under energy shortage conditions, such as over female pubertal development.

Topical ER36009, a RARγ-Selective Retinoid, Decreases Abdominal White Adipose Tissue and Elicits Changes in Expression of Genes Related to Adiposity and Thermogenesis

Chronic topical treatment of rats with a new RARgamma-selective retinoid, ER36009, resulted in a significant reduction of epididymal white adipose tissue and a significant increase of interscapular brown adipose tissue without affecting food intake. ER36009 markedly decreased PPARgamma, 11beta-HSD1, and Bcl-2 mRNA levels, and increased Bax mRNA in white adipose tissue, while it upregulated UCP1 and UCP3 mRNAs in brown adipose tissue and UCP3 mRNA in gastrocnemial muscle. These results suggest that ER36009 has multiple effects on adipose tissue biology and the energy balance. Topically applied ER36009 may have potential for the treatment of obesity.

Fucoxanthin from edible seaweed, Undaria pinnatifida, shows antiobesity effect through UCP1 expression in white adipose tissues

Mitochondrial uncoupling protein 1 (UCP1) is usually expressed only in brown adipose tissue (BAT) and a key molecule for metabolic thermogenesis to avoid an excess of fat accumulation. However, there is little BAT in adult humans. Therefore, UCP1 expression in tissues other than BAT is expected to reduce abdominal fat. Here, we show reduction of abdominal white adipose tissue (WAT) weights in rats and mice by feeding lipids from edible seaweed, Undaria pinnatifida. Clear signals of UCP1 protein and mRNA were detected in WAT of mice fed the Undaria lipids, although there is little expression of UCP1 in WAT of mice fed control diet. The Undaria lipids mainly consisted of glycolipids and seaweed carotenoid, fucoxanthin. In the fucoxanthin-fed mice, WAT weight significantly decreased and UCP1 was clearly expressed in the WAT, while there was no difference in WAT weight and little expression of UCP1 in the glycolipids-fed mice. This result indicates that fucoxanthin upregulates the expression of UCP1 in WAT, which may contribute to reducing WAT weight.

Dietary effect of pomegranate seed oil rich in 9cis, 11trans, 13cis conjugated linolenic acid on lipid metabolism in obese, hyperlipidemic OLETF rats.

Conjugated fatty acid, the general term of positional and geometric isomers of polyunsaturated fatty acids with conjugated double bonds, has attracted considerable attention because of its potentially beneficial biological effects. In the present study, dietary effect of pomegranate seed oil rich in punicic acid (9cis, 11trans, 13cis-conjugated linolenic acid; 9c, 11t, 13c-CLNA) on lipid metabolism was investigated in obese, hyperlipidemic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. After 2 weeks feeding period, OLETF rats revealed obesity and hyperlipidemia compared with their progenitor LETO rats. Feeding of the diet supplemented with 9% safflower oil and 1% pomegranate seed oil (9c, 11t, 13c-CLNA diet) did not affect abdominal white adipose tissue weights and serum lipid levels compared with the diet supplemented with 10% safflower oil (control diet) in OLETF rats. However, the accumulated hepatic triacylglycerol was markedly decreased by 9c, 11t, 13c-CLNA diet in OLETF rats. Activities of hepatic enzymes related to fatty acid synthesis and fatty acid β-oxidation were not altered by 9c, 11t, 13c-CLNA diet. Levels of monounsaturated fatty acid (MUFA), major storage form of fatty acid, in serum triacylglycerol were markedly higher in obese, hyperlipidemic OLETF rats than in lean LETO rats. In addition, 9c, 11t, 13c-CLNA diet significantly decreased MUFA levels in OLETF rats. This is the first study showing that 9c, 11t, 13c-CLNA suppresses delta-9 desaturation in vivo, and we suggest that the alleviation of hepatic triacylglycerol accumulation by 9c, 11t, 13c-CLNA diet was, at least in part, attributable to the suppression of delta-9 desaturation in OLETF rats.

Facial fat and its relationship to abdominal fat: a marker for insulin resistance?

Reports of relationships between measures of insulin sensitivity and measures of body fat and fat distribution suggest that abdominal fat accumulation is a predictor of insulin resistance. It has been previously suggested that facial fat (primarily in the cheeks and neck) is strongly associated with visceral abdominal fat accumulation. The facial fat is a rich vascular region, that seems to be metabolically active and resembles abdominal white adipose tissue. We, therefore, hypothesize that facial fat could be a good predictor of insulin resistance. Whether facial fat can be used as an accurate marker for insulin resistance remains to be determined.

Effects of short-term administration of conjugated linoleic acid on lipid metabolism in white and brown adipose tissues of starved/refed Otsuka Long-Evans Tokushima Fatty rats

The present study explored the short-term effects of dietary conjugated linoleic acid (CLA) on body fat accumulation and lipid metabolism in starved/refed Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Male OLETF rats of 12-weeks-old were starved for 24 h and then re-fed for 48 h either with CLA diet [7.5% CLA and 7.5% safflower oil (SAF)] or SAF control diet (15% SAF oil). The results demonstrated a 27% reduction of white adipose tissue wet weight (total of epididymal and perirenal adipose tissue weight) in the CLA group compared to the control group. The activity of mitochondrial carnitine palmitoyltransferase (CPT), the rate-limiting enzyme for fatty acid oxidation, was significantly elevated by 1.7- and 1.6-fold in perirenal white adipose tissue and interscapular brown adipose tissues, respectively, in the CLA group compared to the control. In contrast, phosphatidate phosphohydrolase (PAP), the rate-limiting enzyme for triglyceride (TG) synthesis, was found to be 23 and 15% lower, in perirenal white- and brown- adipose tissue of CLA-fed rats, respectively. In addition, CLA feeding led to a significant reduced concentration of serum total- and HDL-cholesterol and phospholipid. Thus, dietary CLA evidently lowers abdominal white adipose tissue wet weight through an enhanced fatty acid oxidation and a reduced TG synthesis.

Free fatty acids are involved in the inverse relationship between hormone-sensitive lipase (HSL) activity and expression in adipose tissue after high-fat feeding or beta3-adrenergic stimulation.

The hormone-sensitive lipase (HSL) is the rate-limiting enzyme in adipose tissue lipolysis. The aim of this experimental trial was to study the effects of a beta3-adrenergic agonist (Trecadrine) on plasma fatty acids, adipocyte HSL activity, and gene expression in control and cafeteria-induced obese animals. Control and cafeteria-fed rats were treated with a placebo or Trecadrine during 35 days. Plasma fatty acids were measured by an enzymatic method, whereas HSL activity was assessed by using labeled triolein as substrate. Finally, HSL gene expression from white adipose tissue (WAT) was determined using a reverse transcription-polymerase chain reaction method. Trecadrine administration reduced plasma fatty acids and HSL mRNA levels in abdominal WAT, whereas HSL activity was significantly higher in the Trecadrine-treated obese rats than in the obese nontreated rats. Also, abdominal WAT HSL activity significantly increased, whereas WAT HSL gene expression fell in control rats treated with beta3-adrenergic agonist as compared with control untreated animals. In situations of fat accumulation (high-fat feeding) or lipid mobilization (beta3-adrenergic stimulation), changes in HSL activity and HSL gene expression seem to follow a trend related to plasma fatty acids levels, as indicated by the positive correlation (r = 0.39, p < 0.05) between HSL mRNA levels and plasma fatty acids, and the negative correlation (r = -0.38, p < 0.05) between plasma fatty acids and HSL activity. Furthermore, a highly negative correlation (r = -0.59, p < 0.001) between HSL activity and HSL mRNA expression was found, in which plasma-free fatty acids are apparently involved.

Resistance to aging-associated obesity in capsaicin-desensitized rats one year after treatment.

Previous studies demonstrated reduced weight of abdominal white adipose tissue depots and of carcass fat in capsaicin-desensitized (Cap-Des) rats up to 8 months after treatment. The objective of the present study was to find out whether aging-associated obesity and hyperplasia of retroperitoneal white adipose tissue was prevented in older (13.5 months old) Cap-Des rats, one year after treatment with Cap (done when they were 1.5 months old). The prevalence of obesity is known to increase in rats by this age. Abdominal white adipose tissue depots weighed less in old Cap-Des rats, both epididymal (9% less) and retroperitoneal (30% less). The number of mature white adipocytes was 28% less in the retroperitoneal depot but was not significantly different in the epididymal depot. Adipocyte size was not different. Carcass fat was less, both total and as percent of body weight. Food intake was normal for their reduced body size. The exponential increase in retroperitoneal white adipose tissue weight characteristic of aging rats that are becoming obese was virtually absent in Cap-Des rats. We conclude that lack of function of capsaicin-sensitive afferent autonomic nerves, known to be destroyed in Cap-Des rats, results in an alteration in energy balance conducive to leanness. We suggest that the attenuated age-associated increase in circulating CGRP (derived mainly from capsaicin-sensitive nerves) in the Cap-Des rat results in a lower degree of aging-associated insulin-resistance, hence in a lesser degree of obesity.

Regional variations in metabolic responses of white adipose tissue to food restriction

The effects of food restriction (limited access to food for 2 h/day for 10 days) on lipoprotein lipase (LPL) activities and rates of fatty acid synthesis and glucose utilization in vivo in two superficial (interscapular and subcutaneous) and three deep abdominal white adipose tissue depots (parametrial, perirenal, and mesenteric) of adult female Wistar rats were examined before and at 2 h after a standard laboratory diet meal (5 g). Fasting LPL activities in perirenal (1.6-fold), mesenteric (5.9-fold), and subcutaneous (2.7-fold) adipose tissue, when expressed per unit of delipidated tissue, were increased in response to food restriction. This effect was retained (but not enhanced) after the meal. In contrast, muscle LPL activities were either unchanged or suppressed by food restriction. Stimulation of adipose tissue fatty acid synthesis and glucose utilization evoked by feeding in control rats was greatly enhanced by prior food restriction. There was no relationship between anatomical location and presence or absence of the response of adipose tissue LPL activity to food restriction, but the effect of food restriction to enhance the responses of fatty acid synthesis and glucose utilization to a meal was more marked in perirenal and parametrial adipose tissue than in the more superficial depots. The results thus demonstrate regional specificity in the response of adipose tissue functions to food restriction.

Seasonal weight gain is attenuated in food-restricted ground squirrels with lesions of the suprachiasmatic nuclei.

The role of seasonal hyperphagia in the genesis of prehibernation fattening was assessed in golden-mantled ground squirrels. One group of animals was fed ad lib throughout the weight gain phase of the annual body weight cycle (June-October); a group of neurologically intact animals and one of squirrels with brain lesions incorporating the suprachiasmatic nuclei (SCN) were fed amounts of food equivalent to quantities consumed prior to the body weight trough (May). Part of the seasonal increase of body mass is independent of increases in food consumption; intact animals fed ad lib or restricted to prefattening food intakes underwent similar increases in body mass and possessed equivalent amounts of abdominal white adipose tissue. Food restriction combined with SCN lesions attenuated seasonal weight gain and reduced abdominal fat mass. However, some of the brain-damaged squirrels still evidenced weight gain, a result supporting a previous conclusion that the SCN are involved in circannual body weight rhythm generation but their contribution to this process is not essential for continued rhythmicity in most individuals.

Reduced sympathetic nervous system activity in rats with ventromedial hypothalamic lesions

To determine if alterations in sympathetic nervous system (SNS) activity occur in rats with ventromedial hypothalamic (VMH) lesions, norepinephrine (NE) turnover rates were examined in various tissues of lesioned and control, weanling rats. VMH-lesioned rats fed a high-carbohydrate diet ad libitum for 4 weeks following surgery were not hyperphagic, but they gained 50% more body energy than control rats. VMH lesions extended the half-life of 3H-NE in interscapular brown adipose tissue (BAT) by 42%, in abdominal white adipose tissue (WAT) by 201%, in heart by 61% and in pancreas by 85%, and reduced total NE turnover (ng/organ/hr) in BAT (38%), WAT (57%), heart (30%) and pancreas (53%). Reduced SNS activity in BAT is consistent with the decreased energy expenditure (heat production) and increased energy efficiency observed in VMH-lesioned rats. In WAT, decreased SNS activity coupled with hyperinsulinemia would facilitate energy storage as fat by reducing lipid mobilization. In the pancreas, reduced SNS activity would contribute to hyperinsulinemia. These results support the hypothesis that VMH lesions decrease SNS activity in several organs. This change in autonomic tone is very likely a major factor in the development of obesity in VMH-lesioned animals.