Ventromedial Hypothalamic NPY Y2 Receptor in the Maintenance of Body Weight in Diet-Induced Obesity in Mice

This study examined changes in neuropeptide Y (NPY) Y2 receptor binding in the brains of C57BL/6 mice in response to different levels of high-fat diets via three dietary intervention methods: high-fat diet, switching from high- to low-fat diet and finally, energy restricted high-fat diet. Forty-five C57Bl/6 male mice were fed a high-fat diet for 8 weeks and then classified as diet-induced obese (DIO) or diet-resistant (DR) mice according to the highest and lowest body weight gainers, respectively. The DIO and DR mice were then randomly divided into three groups each and either continued on their high-fat diet ad libitum (DIO-H and DR-H), changed to a low-fat diet (DIO-L and DR-L) or pair-fed via energy restricted high-fat diet (DIO-P and DR-P) for a further 6 weeks. During the course of this study, body weight, energy intake and plasma peptide YY (PYY) were measured. The study revealed that the replacement of a high-fat diet with a low-fat diet was associated with a significant lowering of ventromedial hypothalamic (VMH) Y2 receptor binding in both the DIO-L and DR-L mice (−37%, −36%), and also a lowered plasma PYY level in the DIO-L mice (−25%). Despite a continued consumption of the high-fat diet, energy restricted pair feeding caused a lower VMH Y2 receptor binding in the obese mice (DIO-P) following weight loss compared to the DR-P mice (−14%). In conclusion, this study showed that changing diets from high- to low-fat can significantly lower the VMH Y2 receptor binding irrespective to the obesity phenotype. Energy restriction, even while on high-fat feeding, can cause a lower VMH Y2 receptor binding compared to DR mice even after body weight loss to similar levels. This suggests either a possible intrinsic nature of the DIO mice or a body weight set-point re-establishment to drive body weight regain.     

Higher protein intake preserves lean mass and satiety with weight loss in pre-obese and obese women

Objective: To examine the effects of dietary protein and obesity classification on energy‐restriction‐induced changes in weight, body composition, appetite, mood, and cardiovascular and kidney health. Research Methods and Procedures: Forty‐six women, ages 28 to 80, BMI 26 to 37 kg/m², followed a 12‐week 750‐kcal/d energy‐deficit diet containing higher protein (HP, 30% protein) or normal protein (NP, 18% protein) and were retrospectively subgrouped according to obesity classification [pre‐obese (POB), BMI = 26 to 29.9 kg/m²; obese (OB), BMI = 30 to 37 kg/m²). Results: All subjects lost weight, fat mass, and lean body mass (LBM; p < 0.001). With comparable weight loss, LBM losses were less in HP vs. NP (?1.5 ± 0.3 vs. ?2.8 ± 0.5 kg; p < 0.05) and POB vs. OB (?1.2 ± 0.3 vs. ?2.9 ± 0.4 kg; p < 0.005). The main effects of protein and obesity on LBM changes were independent and additive; POB‐HP lost less LBM vs. OB‐NP (p < 0.05). The energy‐restriction‐induced decline in satiety was less pronounced in HP vs. NP (p < 0.005). Perceived pleasure increased with HP and decreased with NP (p < 0.05). Lipid‐lipoprotein profile and blood pressure improved and kidney function minimally changed with energy restriction (p < 0.05), independently of protein intake. Discussion: Consuming a higher‐protein diet and accomplishing weight loss before becoming obese help women preserve LBM. Use of a higher‐protein diet also improves perceptions of satiety and pleasure during energy restriction.     

Tissue Oxidative Capacity,Fuel Stores and Skeletal Muscle Fatty Acid Composition In Obesity-Prone and Obesity-Resistant Rats

The purpose of the present study was to compare tissue oxidative capacity, skeletal muscle fatty acid composition, and tissue fuel stores in low-fat fed (LFD, 12% of energy from corn oil) male Wistar rats, and in high-fat fed (45% of energy from corn oil) obesity-prone (OP) and obesity-resistant (OR) male Wistar rats. Designation of OP and OR rats was based on body weight gain (upper tertile for OP; lower tertile for OR) after 5 weeks on the high-fat diet. Body weight gain over the 5-week dietary period was 91 ± 9 g in LFD, 98 ± 4 g in OR, and 158 ± 5 g in OP (p<0. 05 vs. LFD and OR). Energy intake over the 5-week dietary period was 3099 ± 101 kcal in LFD, 3185 ± 51 kcal in OR, and 3728 ± 45 kcal in OP (p<0. 05 vs. LFD and OR). Maximal citrate synthase activity (μ. mol^?1min^?1) in the gastrocnemius muscle was not significantly different among groups: 12. 1 ± 2. 4 in LFD, 11. 4 ± 1. 9 in OR and 133 ± 2. 5 in OP rats. Similarly, citrate synthase activity in the heart, 59. 3 ± 7. 2, and liver, 6. 6 ± 0. 4, was also not significantly different among groups. Fatty acid composition of the gastrocnemius muscle was not significantly different among groups. Fasting glycogen levels in the liver, gastrocnemius muscle, and heart were 6. 4 ± 3. 7, 13. 2 ± 2. 3 and 6. 8 ± 1. 9 μmol/g in LFD, 21. 2 ± 5. 1 (p<0. 05 vs. LFD and OP), 10. 4 ± 1. 8 and 5. 9 ± 1. 1 mUmol/g in OR, and 36. 3 ± 4. 8 (p<0. 05 vs. LFD and OR), 10. 2 ± 23 and 53 ± 2. 1 μmol/g in OP rats, respectively. Triglyceride levels were similar among groups in plasma, heart and gastrocnemius muscle, but were significantly (p<0. 05) higher in the liver of OP (15. 5 ± 1. 9 (μmol/g) compared to OR (9. 1 ± 1. 1 μmol/g) and LFD (8. 1 ± 1. 4 μmol/g) rats. These data suggest that susceptibility to dietary obesity, in this rodent model, cannot be explained by differences in tissue oxidative capacity or muscle fatty acid composition.     

Body Fat Accumulation in Zebrafish Is Induced by a Diet Rich in Fat and Reduced by Supplementation with Green Tea Extract

Fat-rich diets not only induce obesity in humans but also make animals obese. Therefore, animals that accumulate body fat in response to a high-fat diet (especially rodents) are commonly used in obesity research. The effect of dietary fat on body fat accumulation is not fully understood in zebrafish, an excellent model of vertebrate lipid metabolism. Here, we explored the effects of dietary fat and green tea extract, which has anti-obesity properties, on body fat accumulation in zebrafish. Adult zebrafish were allocated to four diet groups and over 6 weeks were fed a high-fat diet containing basal diet plus two types of fat or a low-fat diet containing basal diet plus carbohydrate or protein. Another group of adult zebrafish was fed a high-fat diet with or without 5% green tea extract supplementation. Zebrafish fed the high-fat diets had nearly twice the body fat (visceral, subcutaneous, and total fat) volume and body fat volume ratio (body fat volume/body weight) of those fed low-fat diets. There were no differences in body fat accumulation between the two high-fat groups, nor were there any differences between the two low-fat groups. Adding green tea extract to the high-fat diet significantly suppressed body weight, body fat volume, and body fat volume ratio compared with the same diet lacking green tea extract. 3-Hydroxyacyl-coenzyme A dehydrogenase and citrate synthase activity in the liver and skeletal muscle were significantly higher in fish fed the diet supplemented with green tea extract than in those fed the unsupplemented diet. Our results suggest that a diet rich in fat, instead of protein or carbohydrate, induced body fat accumulation in zebrafish with mechanisms that might be similar to those in mammals. Consequently, zebrafish might serve as a good animal model for research into obesity induced by high-fat diets.     

Metabolic Differences in Response to a High-Fat vs. a High-Carbohydrate Diet

Energy expenditure was measured in a group of 7 subjects who received two isocaloric isonitrogenous diets for a period of 9–21 days with a 4–10-day break between diets. Diet 1 was a high-fat diet (83.5 ± 3.6% of total energy). Diet 2 was a high carbohydrate diet (83.1 ± 3.7% of total energy). Resting and postprandial resting metabolic rate were measured by open circuit indirect calorimetry 2–4 times during each metabolic period. Total energy expenditure (TEE) was measured by the doubly labeled water method over an 8–13-day period. The respiratory quotient was measured 2–4 hours after a meal during each metabolic period for the calculation of total energy expenditure by the doubly labeled water method. Levels of total T₃ (TT₃), T₃ uptake, free thyroid index and T₄ were measured at the end of each metabolic period. No significant changes in resting metabolic rate (RMR) were apparent on the two diets (1567 ± 426 kcal/d high-fat diet and 1503 ± 412 kcal/d high-carbohydrate diet n=7, p<0.15). Total energy expenditure measured in 5 subjects was significantly higher during the high-carbohydrate phase of the diet (2443 ± 422 vs. 2078 ± 482 kcal/d p<0.05). Activity estimated from TEE/RMR was greater on the high-carbohydrate diet but only approached statistical significance (p<0.06). Total T₃ was significantly lower and free thyroid index and T₃ uptake were significantly higher at the end of the high fat diet in comparison to the high-carbohydrate diet. These data suggest that individual tolerance to a high-fat diet varies considerably and may significantly lower TEE by changing levels of physical activity. The explanation for changes in thyroid hormone levels independent of changes in metabolic rate remains unclear.     

Improved Psychological Well-Being,Quality of Life,and Health Practices in Moderately Overweight Women Participating in a 12-Week Structured Weight Loss Program

Objective : To study the effects of a 12-week weight loss strategy involving increased physical activity, self-selected hypocaloric diet, and group support on psychological well-being, quality of life, and health practices in moderately obese women. Methods; Eighty women aged 20–49 years weighing between 20–50% above 1983 Metropolitan Life Insurance Tables were randomly assigned to a weight loss intervention (6279 kJ/week of physical activity, 33,258-41,462 kJ/week diet and weekly meetings) or served as controls. Subjects were tested pre and post 12-weeks. Results : The intervention group lost significant (p<0.001) body weight (kg) and body fat (%) compared to controls (-6.07 ± 4.01 kg vs. 1.31 ± 1.28 kg; 36.8%-32.5% vs. 36.2%-36.0%). Intervention subjects vs. controls achieved significant improvements (p<0.001) in body cathexis (X Change 18.6 ± 16.7 vs. 0.7 ± 8.6) and estimation of ability to achieve physical fitness (X Change 8.1 ± 7.1 vs. 0.9 ± 5.9). Various quality of life indices also improved (p<0.01) in the intervention group compared to controls (physical function: X Change 13.5.2 ± 16.7 vs. 1.4 ± 9.5; vitality: X change 21.7 ± 17.9 vs. 2.9 20.8; mental health: X change 10.4 ± 16.0 vs. 2.3 ± 10.1). Similarly, physical activity levels also improved significantly (p<0.0001) in the intervention group (4.4 ± 2.3 vs. 0.6 ± 1.3; on NASA 0–7 scale). Conclusions : Practical weight loss practices such as increased activity, self-selected hypocaloric diet, and group support are effective for weight loss and yield significant health and psychological benefits in moderately obese females.     

Weight Loss During 12 Weeks' Ad Libitum Carbohydrate-Rich Diet in Overweight and Normal-Weight Subjects at a Danish Work Site

The effect of 12 weeks' ad libitum carbohydrate-rich, low-fat diet on total body weight, lean body mass, and fat mass was studied in a group of healthy subjects at a Danish work-site (I) (n=50, BMI = 28.4 ± 0.7 kg/m²). Sixteen subjects served as controls (C) (BMI = 27.0 ± 1.0 kg/m²). After 12 weeks the I subjects had decreased their fat intake from 39.0 ± 1.1 energy-% (E%) to 28.0 ± 1.2 E% and increased their carbohydrate intake from 46.0 ± 1.1 E% to 56.4 ± 1.1 E% (p < 0.05 vs. C). Moreover, a significant loss of body weight (4.2 ± 0.4 kg) and fat mass (4.4 ± 0.6 kg) was observed in I (p < 0.05 vs. C). The weight loss in I was not regained at 24 and 52 weeks' follow-up (82% of I participating) compared to baseline. The cost per kg lost weight amounted to $14.7/person. In conclusion, instructions at a work site in ad libitum intake of a carbohydrate-rich, low-fat diet resulted in a significant loss of body weight and fat mass in overweight and normal-weight subjects.     

Hepatic mitochondrial energetics during catch-up fat with high-fat diets rich in lard or safflower oil

We have investigated whether altered hepatic mitochondrial energetics could explain the differential effects of high-fat diets with low or high ω6 polyunsaturated fatty acid content (lard vs. safflower oil) on the efficiency of body fat recovery (catch-up fat) during refeeding after caloric restriction. After 2 weeks of caloric restriction, rats were isocalorically refed with a low-fat diet (LF) or high-fat diets made from either lard or safflower oil for 1 week, and energy balance and body composition changes were assessed. Hepatic mitochondrial energetics were determined from measurements of liver mitochondrial mass, respiratory capacities, and proton leak. Compared to rats refed the LF, the groups refed high-fat diets showed lower energy expenditure and increased efficiency of fat gain; these differences were less marked with high-safflower oil than with high-lard diet. The increase in efficiency of catch-up fat by the high-fat diets could not be attributed to differences in liver mitochondrial activity. By contrast, the lower fat gain with high-safflower oil than with high-lard diet is accompanied by higher mitochondrial proton leak and increased proportion of arachidonic acid in mitochondrial membranes. In conclusion, the higher efficiency for catch-up fat on high-lard diet than on LF cannot be explained by altered hepatic mitochondrial energetics. By contrast, the ability of the high-safflower oil diet to produce a less pronounced increase in the efficiency of catch-up fat may partly reside in increased incorporation of arachidonic acid in hepatic mitochondrial membranes, leading to enhanced proton leak and mitochondrial uncoupling.     

Effects of Weight Cycling Induced by Diet Cycling in Rats Differing in Susceptibility to Dietary Obesity

LAUER, JOAN B., GEORGE W. REED, AND JAMES O. HILL. Effects of weight cycling induced by diet cycling in rats differing in susceptibility to dietary obesity. Obes Res. Objective Although the majority of evidence in rodents does not support the view that weight cycling (consisting of bouts of food restriction and refeeding) promotes obesity, the effects of weight cycling on body weight regulation remain controversial. We have previously demonstrated that some rats within a strain are more susceptible to develop obesity than others when given free access to a high-fat diet. In this study, we tested the hypothesis that rats most susceptible to weight gain on a high-fat diet would also be most susceptible to weight gain as a consequence of weight cycling. Research Methods and Procedures Rats were provided a low-fat diet (12% corn oil) for 2 weeks, then given a high-fat diet (45% corn oil) for 2 weeks to identify those most (obesity prone) and least (obesity resistant) susceptible to weight gain. Half of each group was then subjected to three 30-day cycles of food restriction (10 days) and refeeding (20 days) [weight cycler (WC) rats]. The other half were allowed free access to the high-fat diet [control (CO) rats]. All rats were then followed for an additional 10 weeks, with free access to the high-fat diet. Results When considering the entire 160 days of the study, we found no evidence that WC rats relative to CO rats had increased body weight, increased body fat content, or elevated energy efficiency. We found no evidence that rats most prone to dietary obesity were also prone to weight gain after weight cycling. During the weight cycling phase (days 1 to 90), weight cycled groups consumed less energy and gained less weight than controls. During the follow-up phase, WC and CO rats did not differ significantly in weight gain or energy intake. Discussion In this study, weight cycling did not exacerbate the obesity produced by high-fat diet feeding.     

Composition of Dietary Fat Affects Blood Pressure and Insulin Responses to Dietary Obesity in the Dog

Cardiovascular and metabolic parameters were evaluated in 15 female spayed dogs before and after they became obese on either a saturated fat (LD, lard, n=8) or unsaturated fat (CO, corn oil, n=7) diet. Body weight and body fat increased significantly in both groups, although no differences occurred between diet groups. Dogs receiving the LD diet exhibited a greater increase in mean arterial pressure than those receiving the CO diet (p<0. 01; 15. 9 ± 2. 1 vs. 9. 8 ± 3. 3 mm Hg increase). The CO diet stimulated a greater increase in heart rate than the LD diet (p<0. 05; 32. 8 ± 7. 8 vs. 14. 1 ± 5. 8 bpm increase). Ganglionic blockade with chlorisondamine caused an increase in HR in both lean groups and in the obese CO group, but not the obese LD group, consistent with a decrease in parasympathetic tone to the heart in the dogs overfed saturated fat. Obesity enhanced the heart rate response to β-badrenergic stimulation by isoproterenol in the LD, but not CO group. The LD diet increased circulating insulin and decreased insulin sensitivity, whereas the CO diet had no effect on either parameter. These findings suggest that the composition of dietary fat can modulate the autonomic and metabolic adaptations induced by dietary obesity.     

Role of β2‐Adrenergic Receptor Polymorphisms on Body Weight and Body Composition Response to Energy Restriction in Obese Women: Preliminary Results

We investigated the role of common β2‐adrenergic receptor (ADRB2) rs1042714 (Gln27Glu) and rs1042713 (Arg16Gly) polymorphisms on body weight and body composition response to 12‐week energy‐restricted diet in women. The study comprised 78 Spanish obese (BMI: 34.0 ± 2.8 kg/m²) women (age: 36.7 ± 7 years). We measured (before and after the dietary intervention) weight and height, and BMI calculated. Moreover, body fat mass and lean mass (LM) were measured by dual energy X‐ray absorptiometry. We observed an interaction effect between the Gln27Glu polymorphism and diet‐induced changes on body weight (P = 0.006), BMI (P = 0.004), and LM (P = 0.001). Women carrying the Glu allele had a greater reduction in body weight than non‐Glu allele carriers (9.5 ± 2.9 vs. 7.0 ± 3.5%, respectively, P = 0.002). Moreover, women with the Glu allele lost more LM than the Gln27Gln group (5.9 ± 2.7 vs. 4.0 ± 2.7%, respectively, P = 0.001). We did not find any significant interaction effect between the Arg16Gly polymorphism and diet‐induced changes on the outcome variables (all P > 0.1). The results suggest that the ADRB2 Gln27Glu polymorphism has a modulating effect on diet‐induced changes on body weight and body composition, and should be considered in future obesity treatments. These findings should be taken as preliminary and be replicated in further energy restriction studies with larger sample sizes.     

Acute changes in the response to peripheral leptin with alteration in the diet composition

Dietary induced obesity in rodents is associated with a resistance to leptin. We have investigated the hypothesis that dietary fat per se alters the feeding response to peripheral leptin in rats that were fed either their habitual high- or low-fat diet or were naively exposed to the alternative diet. Osborne-Mendel rats were adapted to either high- or low-fat diet. Food-deprived rats were given either leptin (0.5 mg/kg body wt ip) or saline, after which they were provided with either their familiar diet or the alternative diet. Food intake of rats adapted and tested with the low-fat diet was reduced 4 h after leptin injection, whereas rats adapted and tested with a high-fat diet did not respond to leptin. Leptin was injected again 1 and 5 days after the high-fat diet-adapted rats were switched to the low-fat diet. Leptin reduced the food intake on both days. In contrast, when low-fat diet-adapted rats were switched to a high-fat diet, the leptin inhibitory response was present on day 1 but not observed on day 5. Peripheral injection of leptin increased serum corticosterone level and decreased hypothalamic neuropeptide Y mRNA expression in rats fed the low-fat but not the high-fat diet for 20 days. The data suggest that dietary fat itself, rather than obesity, may induce leptin resistance within a short time of exposure to a high-fat diet.     

Energy restriction in obese subjects impact differently two mitochondrial function markers

Excessive fat deposition is the key feature in obesity, which is empowered by cytokines overproduction and stimulation of cell oxidative stress processes, but little is known about energy availability in the form of ATP and mitochondrial function in the obese subjects. Thus, the aim of this study was to evaluate the possible changes in energy metabolism after a 8-weeks balanced-hypocaloric diet in obese subjects by measuring the ATP-content in leukocytes, by assessing 2-keto [1-¹³C] isocaproate breath test (KICA-BT) parameters related to mitochondrial function and by analyzing inflammatory and oxidative stress biomarkers. All the recruited obese subjects (n=19) lost body weight after dieting (−5.55±2.88%). The hypocaloric treatment induced a decrease in leptin levels and lipid peroxidation markers. Interestingly, the ATP content in blood leukocytes increased (49.9±32.5 vs 36.2±27.9 pmol/mg prot.; p<0.05), while KICA tracer mitochondrial oxidation decreased (30.9±5.9 vs. 33.1±4.5%¹³C; p<0.05) after weight loss. These results show that two minimally invasive methods were able to detect changes in mitochondrial function as induced by a hypocaloric diet, which is of great interest in order to understand oxidative processes associated with weight homeostasis as well as to establish newer anti-obesity therapeutic targets by using mitochondrial function markers in vivo.     

Programmed metabolic syndrome: prenatal undernutrition and postweaning overnutrition

Maternal nutrient restriction results in intrauterine growth restriction (IUGR) newborns that develop obesity despite normal postweaning diet. The epidemic of metabolic syndrome is attributed to programmed "thrifty phenotype" and exposure to Western diets. We hypothesized that programmed IUGR newborns would demonstrate greater susceptibility to obesity and metabolic abnormalities in response to high-fat diet. From day 10 to term gestation and lactation, control pregnant rats received ad libitum (AdLib) food, whereas study rats were 50% food restricted (FR). Cross-fostering techniques resulted in three offspring groups: control (AdLib/AdLib), FR during pregnancy (FR/AdLib), and FR during lactation (AdLib/FR). At 3 weeks, offspring were weaned to laboratory chow or high-fat calorie diet (9% vs. 17% calorie as fat). Body composition, appetite hormones, and glucose and lipid profiles were determined in 9-mo-old male and female offspring. High-fat diet had no effect on body weight of AdLib/AdLib, but significantly increased weights of FR/AdLib and AdLib/FR offspring. High-fat diet significantly increased body fat, reduced lean body mass, and accentuated plasma leptin but not ghrelin levels in both sexes in all groups. In males, high-fat diet caused a significant increase in glucose levels in all three groups with increased insulin levels in AdLib/AdLib and AdLib/FR, but not in FR/AdLib. In females, high-fat diet had no effect on glucose but significantly increased basal insulin among all three groups. High-fat diet caused hypertriglyceridemia in all three groups although only food-restricted females exhibited hypercholesterolemia. Sex and offspring phenotype-associated effects of high-fat diet indicate differing pathophysiologic mechanisms that require specific therapeutic approaches.     

Effect of Age on Protein Conservation during Very-Low-Energy Diet in Obese Sprague-Dawley Rats

JOHNSON, JULIA A, CHOON-HIE YU, MEI-UIH YANG, F. XAVIER PI-SUNYER. Effect of age on protein conservation during very-low-energy diet in obese Sprague-Dawley rats. Obes. Res. 1998;6:448-157. Objective : To examine the effect of age on body protein losses occurring during severe energy restriction in obesity. Research Methods and Procedures : Weanling (young) Sprague-Dawley rats (YR) were fed a high fat (35% energy) diet (HFD) until mean body weight approached that of a group of chowfed retired breeder (aged) rats (AR). Both groups were then fed HFD for an additional 2 weeks, after which selected controls from YR and AR groups were killed for baseline carcass analysis. Remaining rats were fed a very-low-energy diet (VLED, 33% kcal of HFD) for 3 weeks and then killed for carcass analysis. Results : YR had greater fat stores before VLED, and lost proportionately more fat and less protein during VLED than did AR. Weight loss composition during VLED was 66.7% fat, 11.1% protein, and 22.2% water in YR, and 39.4% fat, 26.2% protein, and 34.3% water in AR. Greater YR fat loss during VLED* (70.6 ± 30.4 vs. 32.6 ± 29.1 g in AR; mean ± SD) was paralleled by significantly larger decreases in epididymal and retroperitoneal fat pad weights, mean adipocyte size, and lipoprotein lipase activity. Greater protein loss in AR (21.6 ± 13.9 g vs. 11.8 ± 10.7 g in YR) coincided with larger decreases in visceral organ weights and serum thyroxine and triiodothyronine. Energy expenditure changes during VLED were similar between groups. Discussion : Dietary obese young rats appear better able than aged rats to conserve body protein while losing body fat during severe energy restriction.     

Effect of a selective OX1R antagonist on food intake and body weight in two strains of rats that differ in susceptibility to dietary-induced obesity

An orexin-1 receptor antagonist decreases food intake whereas orexin-A selectively induces hyperphagia to a high-fat diet. In the present study, we evaluated the effect of an orexin antagonist in two strains of rats that differ in their sensitivity to becoming obese while eating a high-fat diet. Male Osborne-Mendel (OM) and S5B/Pl (S5B) rats were treated acutely with an orexin-1 receptor antagonist (SB-334867), after adaptation to either a high-fat (56% fat energy) diet or a low-fat (10% fat energy) diet that were equicaloric for protein (24% energy). Ad libitum fed rats were injected intraperitoneally with SB-334867 at doses of 3, 10 or 30 mg/kg, or vehicle at the beginning of the dark cycle, and food intake and body weight were measured. Hypothalamic prepro-orexin and orexin-1 receptor mRNA expression were analyzed in OM and S5B rats fed at a high-fat or low-fat diet for two weeks. SB-334867 significantly decreased food intake in both strains of rats eating the high-fat diet but only in the OM rats eating the low fat diet. The effect was greatest at 12 and 24 h. Body weight was also reduced in OM rats 1d after injection of SB-334867 but not in the S5B rats. Prepro-orexin and orexin-1 receptor expression levels did not differ between strains or diets. These experiments demonstrate that an orexin antagonist (SB-334867) reduces food intake and has a greater effect in a rat strain that is susceptible to dietary-induced obesity, than in a resistant strain.     

Changes in gene expression foreshadow diet-induced obesity in genetically identical mice

High phenotypic variation in diet-induced obesity in male C57BL/6J inbred mice suggests a molecular model to investigate non-genetic mechanisms of obesity. Feeding mice a high-fat diet beginning at 8 wk of age resulted in a 4-fold difference in adiposity. The phenotypes of mice characteristic of high or low gainers were evident by 6 wk of age, when mice were still on a low-fat diet; they were amplified after being switched to the high-fat diet and persisted even after the obesogenic protocol was interrupted with a calorically restricted, low-fat chow diet. Accordingly, susceptibility to diet-induced obesity in genetically identical mice is a stable phenotype that can be detected in mice shortly after weaning. Chronologically, differences in adiposity preceded those of feeding efficiency and food intake, suggesting that observed difference in leptin secretion is a factor in determining phenotypes related to food intake. Gene expression analyses of adipose tissue and hypothalamus from mice with low and high weight gain, by microarray and qRT-PCR, showed major changes in the expression of genes of Wnt signaling and tissue re-modeling in adipose tissue. In particular, elevated expression of SFRP5, an inhibitor of Wnt signaling, the imprinted gene MEST and BMP3 may be causally linked to fat mass expansion, since differences in gene expression observed in biopsies of epididymal fat at 7 wk of age (before the high-fat diet) correlated with adiposity after 8 wk on a high-fat diet. We propose that C57BL/6J mice have the phenotypic characteristics suitable for a model to investigate epigenetic mechanisms within adipose tissue that underlie diet-induced obesity.     

Resveratrol does not increase body fat loss induced by energy restriction

Resveratrol (RSV) is known to have an antiobesogenic effect because it mimics energy restriction. However, hardly any evidence exists concerning the combined effects of RSV and energy restriction on body fat reduction. So, the aim of the present study was to determine whether RSV increases body fat reduction induced by energy restriction. Male Wistar rats were fed a high-fat, high-sucrose diet for 6 weeks to obtain a diet-induced obesity model. Then they were submitted to a mild energy restriction (25 %) without or with RSV supplementation (30 mg/kg body weight/day) for 2 weeks. Final body weight, subcutaneous and intra-abdominal white adipose tissues weights, Adipose Index, and serum triacylglycerol, cholesterol, glucose, and insulin were assessed. Lipoprotein lipase (LPL), fatty acid synthase (FAS), and acetyl coenzyme A carboxylase (ACC) activities, as well as their genetic expressions, were measured in white adipose tissue. Final body weight, white adipose tissue weights, Adipose Index, and serum triacylglycerol, cholesterol, and insulin were reduced in both groups, but no differences were found among them. FAS, ACC, and LPL activities and expressions were also similar in both groups. These results suggest a lack of any adjuvant effect of RSV on energy restriction for obesity treatment purposes.