Effects of different weight loss protocols on serum leptin levels in obese females

We investigated the effects of different weight loss protocols on leptin levels in obese females with the aim of addressing the leptin resistance which has been found to be an aggravating factor in obesity. Twenty-four obese females enrolled to one of three 12-week weight loss protocols: orlistat-induced weight loss (OWL, n=8), exercise-induced weight loss (EWL, n=8) and orlistat plus exercise-induced weight loss (OEWL, n=8). Serum leptin levels were measured in duplicate by radioimmunoassay. There were significant reductions (P<0.01) in body weight and fat mass after the 12 week period in all groups: -11.4+/-0.5 kg and -9.8+/-0.5 kg (OEWL), -8.3+/-0.8 kg and -5.7+/-0.9 kg (OWL), -8.9+/-1.2 kg and -7.4+/-1.2 kg (EWL), respectively. Serum leptin levels were also decreased markedly in all groups: -59.2 % (OEWL1), -37.8 % (OWL) and -48.6 % (EWL) (P<0.01 all). In addition, there were marked decreases in leptin levels for each kilogram of fat mass after the 12 week period: -48.2+/-7.2 % (OEWL), -27.8+/-4.8 % (OWL) and -39.3+/-4.3 % (EWL) (P<0.01 all). Decreases in serum leptin levels expressed per kilogram of fat mass were significantly higher in the OEWL group compared to the OWL group (P=0.03). Consequently, an exercise training program in adjunct to pharmacotherapy provides higher weight reduction and fat mass loss in obesity treatment. It also seems to have further beneficial effects on leptin resistance, as indicated by decreases in leptin levels expressed per kilogram of fat mass.     

Effects of weight loss on erythrocyte membrane composition and fluidity in overweight and moderately obese women

A previous study showed chemical and physical impairment of the erythrocyte membrane of overweight and moderately obese women. The present study investigated the effects of a low-calorie diet (800 kcal/day deficit for 8 weeks) on erythrocyte membrane properties in 70 overweight and moderately obese (body mass index, 25-33 kg/m²) normotensive, nondiabetic women. At the end of dietary intervention, 24.3% of women dropped out, 45.7% lost less than 5% of their initial weight (Group I) and only 30% of patients lost at least 5% of their initial body weight (Group II). Group I showed no significant changes in erythrocyte membrane composition and function. The erythrocyte membranes of Group II showed significant reductions in malondialdehyde, lipofuscin, cholesterol, sphingomyelin, palmitic acid and nervonic acid and an increase in di-homo-γ-linolenic acid, arachidonic acid and membrane fluidity. Moreover, Group II showed an improvement in total cholesterol, low-density lipoprotein cholesterol, glycemia and insulin resistance. These changes in erythrocyte membrane composition could reflect a virtuous cycle resulting from the reduction in insulin resistance associated with increased membrane fluidity that, in turn, results in a sequence of metabolic events that concur to further improve membrane fluidity.     

Pancreatic polypeptide causes diarrhea and weight loss in obese mice but not in lean littermates

Pancreatic polypeptide was infused into obese-hyperglycemic (ob/ob) mice and lean littermates to determine its effect on weight gain. Obese mice continuously infused with 30, 60, or 100 μg/day for 7 days developed both diarrhea and weight loss in a dose dependent fashion. Lean littermates infused with 100 μg/day developed neither diarrhea nor weight loss. Light microscopic study of ileum and colon revealed no abnormalities. These studies indicate that the effects of pancreatic polypeptide are in part genetically determined since the obese and non-obese mice differ at only one gene locus.     

Effects of low calorie diet-induced weight loss on post-exercise heart rate recovery in obese men

[Purpose]

Heart Rate Recovery (HRR) after maximum exercise is a reactivation function of vagus nerve and an independent risk factor that predicts cardiovascular disease and mortality. Weight loss obtained through dietary programs has been employed as a therapy to reduce risks of cardiovascular disease and obesity.

[Methods]

Eighteen subjects of middle aged obese men (age 44.8 ± 1.6 yrs, BMI 29.7 ± 0.5 kg/m²) were selected for this study. As a weight loss direction, the nutritional direction of low-calorie diet mainly consisted of carbohydrate, protein, and fat has been conducted for 3 months. Blood pressure was measured after overnight fasting, and blood samples were collected from the antecubital vein before and after weight loss program. All the pre- and post-exercise ‘HRR decay constant’s were assessed by using values of HRR (heart recovery rate; 2 minutes) and HR measured after reached to the maximal oxygen uptake (VO₂max) exploited the bicycle ergometer.

[Results]

After the completion of weight loss program, body weight and BMI were significantly decreased, but the Heart Rate (HR) after maximum exercise and in steady state were not changed significantly (p > 0.05). The post-exercise HRR after the weight loss did not show significant changes in perspectives of 30 seconds (-16.6 ± 2.3 to -20.2 ± 2.1 beats/min, p > 0.05) and 60 seconds (-33.5 ± 3.4 to -34.6 ± 2.8 beats/min, p > 0.05) respectively but in perspectives of 90 seconds (-40.9 ± 2.6 to -48.1 ± 3.1 beats/min, p < 0.05) and 120 seconds (-48.6 ± 2.6 to -54.3 ± 3.5 beats/min, p < 0.05), they were decreased significantly. Pre-’HRR decay constant’s of 0.294 ± 0.02 %/second were significantly increased to post-values of 0.342 ± 0.03 %/second (p = 0.026). Changes in ‘HRR decay constant’ were significantly correlated with changes in blood glucose (r = -0.471, p < 0.05) and maximal oxygen consumption (VO₂max, r = 0.505, p < 0.05) respectively.

[Conclusions]

The low-calorie diet directed to obese middle aged men for 3 months significantly improved the HRR after maximum exercise, and this improvement in cardiovascular autonomic nerve system was estimated to be involved with improvements in blood glucose and maximal oxygen consumption.     

Influences of weight loss on monocytes and T-cell subpopulations in male judo athletes

The purpose of this study was to examine weight loss effects on immune function in judo athletes. Six elite male Japanese judo athletes (20.3 ± 0.4 years) were enrolled in this study. They completed usual weight loss programs during 2 weeks preceding an actual competition. Subjects noted the appearance of upper-respiratory tract infection (URTI) symptoms during the study period. Blood samples were obtained at 40 (baseline period: BL) and 3 (weight loss period: WL) days before and 1 day after the competition (AC). The CD3, CD4, CD8, CD56CD3, CD28CD4, CD28CD8, and Toll-like-receptor-4 (TLR-4) CD14 cells were counted by using flow cytometer analysis. The 6 subjects reported 1 headache, 3 runny nose conditions, and 1 coughing instance during the WL. The CD3, CD4, CD8, and CD28CD4 cell counts were significantly lower at WL than at BL (p ≤ 0.05); they reverted to the baseline value at AC. The TLR-4CD14 cells were significantly fewer at WL (p ≤ 0.05); they remained fewer than they had been at BL, even at AC. These results suggest that 2 weeks of weight loss before a competition can impair cell-mediated immune function and induce high susceptibility to URTI in judo athletes. Coaches, support staff, and athletes should monitor athletes' weight loss, hydration status, appearance of URTI symptoms, and immunocompetence such as lymphocytes and monocytes to prevent the physical condition from becoming worse.     

Adrenal androgens in obese boys before and after weight loss

The adrenal steroid secretion was studied in 6 prepubertal obese boys and 6 obese boys at the first stage of sexual maturation according to Tanner. Twelve normal boys, closely matched for age and stage of sexual maturation, were also studied as controls. Pregnenolone and dehydroepiandrosterone plasma levels were found to be significantly (P less than 0.001) higher in both groups when compared with normal boys. All the values, apart from pregnenolone in the prepubertal group, returned to normal after weight loss. Progesterone was found significantly increased (P less than 0.001) in both groups and normal after weight loss. 17-OH-progesterone plasma levels showed no significant difference between the obese and control groups. Androstenedione was increased in the prepubertal group before and normal after weight loss; no significant difference was found in the other group. Testosterone and estradiol showed normal values in the two groups both before and after weight loss. Cortisol showed a similar pattern. It can be concluded that an increased cortico-adrenal activity is present in obese boys as already reported in obese girls. This finding could explain the precocious adrenarche which often occurs in these patients. The increased adrenal androgen secretion might be due to an increased cortico adrenal stimulating hormone secretion or to an enhanced adrenal sensitivity to this hypothetical hormone.     

Hyperleptinemia in obese adolescents deregulates neuropeptides during weight loss

Leptin has emerged over the past decade as a key hormone not only in energy balance regulation but also in neuroendocrine and inflammatory processes. The aim of the present study was to evaluate whether hyperleptinemia deregulates neuropeptides during weight loss. A total of 86 post-pubertal obese adolescents (with or without hyperleptinemia) participated in one year of interdisciplinary weight loss therapy (clinical, nutritional, psychological and exercise-related). Adipokine and neuropeptide concentrations were measured by ELISA, visceral fat was measured by ultrasound and body composition was measured by pletismography. The hyperleptinemic patients presented a lower alpha-MSH concentration and higher NPY/AgRP ratio while the adiponectin/leptin (A/L) ratio was lower compared with the non-hyperleptinemic group. After therapy, significant improvements in BM, BMI, body fat mass, visceral and subcutaneous fat, HOMA-IR, QUICKI, total cholesterol and triglycerides were observed in both groups. Indeed, we observed significant increases in adiponectin and A/L as well as reductions in leptin and NPY/AgRP ratio in the hyperleptinemic group. In the stepwise multiple linear regression analysis with leptin concentration as the dependent variable, α-MSH and body fat mass (%) were the independent predictors to explain leptin concentration. For the entire group, we found positive correlations between leptinemia and BMI and body fat mass (%) as well as a negative correlation with free fat mass (%) and alpha-MSH. Finally, we verified negative correlations between adiponectin/leptin ratio with total cholesterol and LDL-c, only in hyperleptinemic patients. In conclusion, the hyperleptinemia in obese adolescents deregulates neuropeptides during weight loss.     

Effects of physical exercise on butyrylcholinesterase in obese adolescents

The aim of the present study was to evaluate the effect of a 12 week program of physical exercise (PE) on butyrylcholinesterase (BChE) in obese adolescents. This study compared obese adolescents (N = 54) before and after PE, regarding the relative intensity (RI) and activity of different molecular forms (G1, G2, G4 and G1-ALB) of BChE found in plasma. Waist circumference (WC) and lipid profile were also assessed before and after PE. It was shown that before PE, mean plasma BChE activity was significantly higher in obese than in non-obese adolescents and that it was significantly reduced after PE, becoming similar to that found in non-obese adolescents. Lipid profile and WC also changed in response to PE. These results are consistent with studies that found a correlation between BChE and lipid metabolism and suggest that PE may have led to a physiological regularization of plasma BChE activity. Although mean BChE activity of each isoform was significantly reduced by PE, their RI did not change. This is in accordance with a previous suggestion that this proportion is maintained under factors such as obesity, and may therefore be important for BChE functions.     

Effect of weight loss on muscle lipid content in morbidly obese subjects

The purpose of this study was to test the hypothesis that weight loss results in a reduction in intramuscular lipid (IMCL) content that is concomitant with enhanced insulin action. Muscle biopsies were obtained from morbidly obese individuals [body mass index (BMI) 52.2 +/- 2.5 kg/m(2); n = 6] before and after gastric bypass surgery, an intervention that improves insulin action. With intervention, there was a 47% reduction (P < 0.01) in BMI and a 93% decrease in homeostasis model assessment, or HOMA (7.0 +/- 1.9 vs. 0.5 +/- 0.1). Histochemically determined IMCL content decreased (P < 0.05) by approximately 30%. In relation to fiber type, IMCL was significantly higher in type I vs. type II fibers. In both fiber types, there were reductions in IMCL and trends for muscle atrophy. Despite these two negating factors, the IMCL-to-fiber area ratio still decreased by approximately 44% with weight loss. In conclusion, despite differing initial levels and possible atrophy, weight loss appears to decrease IMCL deposition to a similar relative extent in type I and II muscle fibers. This reduction in intramuscular triglyceride may contribute to enhanced insulin action seen with weight loss.     

Effects of weight loss in metabolically healthy obese subjects after laparoscopic adjustable gastric banding and hypocaloric diet

Weight loss in metabolically healthy obese (MHO) subjects may result in deterioration of cardio-metabolic risk profile. We analyzed the effects of weight loss induced by laparoscopic adjustable gastric banding (LAGB) on cardio-metabolic risk factors in MHO and insulin resistant obese (IRO) individuals. This study included 190 morbidly obese non-diabetic subjects. Obese individuals were stratified on the basis of their insulin sensitivity index (ISI), estimated from an OGTT, into MHO (ISI index in the upper quartile) and IRO (ISI in the three lower quartiles). Anthropometric and cardio-metabolic variables were measured at baseline and 6-months after LAGB. Six months after LAGB, anthropometric measures were significantly reduced in both MHO and IRO. Percent changes in body weight, BMI, and waist circumference did not differ between the two groups. Fasting glucose and insulin levels, triglycerides, AST, and ALT were significantly reduced, and HDL cholesterol significantly increased, in both MHO and IRO subjects with no differences in percent changes from baseline. Insulin sensitivity increased in both MHO and IRO group. Insulin secretion was significantly reduced in the IRO group only. However, the disposition index significantly increased in both MHO and IRO individuals with no differences in percent changes from baseline between the two groups. The change in insulin sensitivity correlated with the change in BMI (r = −0.43; P<0.0001). In conclusion, our findings reinforce the recommendation that weight loss in response to LAGB intervention should be considered an appropriate treatment option for morbidly obese individuals regardless of their metabolic status, i.e. MHO vs. IRO subjects.     

Separate and combined effects of exercise training and weight loss on exercise efficiency and substrate oxidation

Perturbations in body weight have been shown to affect energy expenditure and efficiency during physical activity. The separate effects of weight loss and exercise training on exercise efficiency or the proportion of energy derived from fat oxidation during physical activity, however, are not known. The purpose of this study was to determine the separate and combined effects of exercise training and weight loss on metabolic efficiency, economy (EC), and fat oxidation during steady-state moderate submaximal exercise. Sixty-four sedentary older (67 +/- 0.5 yr) overweight to obese (30.7 +/- 0.4 kg/m(2)) volunteers completed 4 mo of either diet-induced weight loss (WL; n = 11), exercise training (EX; n = 36), or the combination of both interventions (WLEX; n = 17). Energy expenditure, gross efficiency (GE), EC, and proportion of energy expended from fat (EF) were determined during a 1-h submaximal (50% of peak aerobic capacity) cycle ergometry exercise before the intervention and at the same absolute work rate after the intervention. We found that EX increased GE by 4.7 +/- 2.2%. EC was similarly increased by 4.2 +/- 2.1% by EX. The addition of concomitant WL to EX (WLEX) resulted in greater increases in GE (9.0 +/- 3.3%) compared with WL alone but not compared with EX alone. These effects remained after adjusting for changes in lean body mass. The proportion of energy derived from fat during the bout of moderate exercise increased with EX and WLEX but not with WL. From these findings, we conclude that exercise training, either alone or in combination with weight loss, increases both exercise efficiency and the utilization of fat during moderate physical activity in previously sedentary, obese older adults. Weight loss alone, however, significantly improves neither efficiency nor utilization of fat during exercise.     

Kinematic and kinetic changes in obese gait in bariatric surgery-induced weight loss

This study examines the effects of a radical bariatric surgery-induced weight loss on the gait of obese subjects. We performed a three-dimensional motion analysis of lower limbs, and collected force platform data in the gait laboratory to calculate knee and hip joint moments. Subjects (n=13) performed walking trials in the laboratory before and 8.8 months (SD 4.2) after the surgical procedure at two gait speeds (1.2m/s and 1.5m/s). The average weight loss was 26.7kg (SD 9.2kg), corresponding to 21.5% (SD 6.8%) of the initial weight. We observed a decrease in step width at both gait speeds, but no changes in relative double support or swing time or stride length. A significant decrease was noted in the absolute values of peak knee abductor, peak knee flexor and peak hip extensor moments. However, the moment values normalized by the body weight and height remained unchanged in most cases. Thus, we conclude that weight loss reduces hip and knee joint moments in proportion to the amount of weight lost.     

Maintenance of weight loss in obese patients after jaw wiring.

In treatment of obesity restriction of food intake is necessary to achieve good results. Various operations have been devised to prevent patients overeating, but in this study jaw wiring was used to limit food intake. This procedure produces weight loss in obese patients but when the wires are removed the weight is usually regained. This report studied a group of patients whose weight loss was maintained after the wires were removed. A nylon cord fastened round the waist of the patient after weight reduction was found to act as a psychological barrier to weight gain. Seven patients were followed for 4-14 months after removal of jaw wires and regained a mean of only 5.6 kg of the 31.8 kg lost while their jaws were wired. This procedure compares favourably with other treatments for severe obesity.     

Effects of estrogen on food intake, body weight, and temperature of male and female obese mice

Estradiol benzoate (EB) treatment of male and female C57BL/6J ob/ob mice for 32 days led to decreased body weight (20%), percentage body fat (8%) and carcass protein content (12%) when compared with non-EB-treated obese control mice. Estradiol reduced the caloric intakes of both genders by 25-35%, but did not affect body temperature regulation. Circulating glucose and insulin concentrations were also lowered by estrogens, although hyperinsulinemia persisted. Since post-treatment body weight changes correlated with daily food intakes (r = 0.81) rather than to rectal temperatures (r = -0.19), it appears that hypophagia provided a greater contribution to the estrogen-mediated reductions of growth and carcass fat than did altered energy expenditure for thermoregulation. While these data show that EB treatment does reduce the severity of some metabolic disturbances in a genetic model of type II diabetes, long-term estrogens do not appear to offer substantial advantages in the treatment of obesity or diabetes when compared with the effects of caloric restriction alone.     

Effects of aerobic exercise on serum leptin levels in obese women

It has been demonstrated that leptin concentrations in obese patients may be altered by weight loss. We examined the effects of a 9-week aerobic exercise program on serum leptin concentrations in overweight women (20-50% above ideal body mass) under conditions of weight stability. Sixteen overweight women, mean (SE) age 42.75 (1.64) years, comprised the exercise group which adhered to a supervised aerobic exercise program. A graded exercise treadmill test was conducted before and after the exercise program to determine maximal oxygen uptake (VO2max) using open-circuit spirometry. The women demonstrated improved aerobic fitness (VO2max increased 12.29%), however, body fat and the body mass index did not change significantly [42.27 (1.35)-41.87 (1.33)%]. Fourteen women, age 40.57 (2.80) years, did not exercise over the same time period and served as a control group. Serum leptin levels were not significantly altered for either the exercise [28.00 (2.13)-31.04 (2.71) ng x ml(-1)] or the control group [33.24 (3.78)-34.69 (3.14) ng x mg(-1)]. The data indicate that 9 weeks of aerobic exercise improves aerobic fitness, but does not affect leptin concentrations in overweight women.     

VLCD-induced weight loss improves heart rate variability in moderately obese Japanese

To evaluate the effects of weight reduction on the autonomic nervous system in obese patients, we investigated heart rate variability (HRV) based on 24-hr ambulatory electrocardiogram (ECG) recordings before and after weight reduction. To aim for weight reduction, 16 obese patients were treated with the very-low-calorie conventional Japanese diet (VLCD-CJ) therapy combined with behavior therapy. Percent weight reduction was 17.8% +/- 1.5% (means +/- SEM), but mean blood pressure did not change significantly after VLCD-CJ therapy. The mean normal R-R interval (mNN) of the 24-hr ECG and all other five time-domain indices increased after weight reduction. Spectral analysis revealed that weight reduction increased the high frequency (HF) component, but decreased the ratio of low to high (LF/HF) components. Rate of change in mNN or HF correlated positively with reduction rate of body mass index, but not that in LF/HF. Analysis of daily fluctuations in each HRV parameter showed that significant improvement after weight loss occurred mainly during the nocturnal period, but an HF component was improved throughout the day and night periods. These findings indicate that functional impairment of the autonomic nervous system in obese subjects, particularly in the nocturnal period, is improved by effective weight reduction after VLCD-CJ therapy.     

Metabolomic response to exercise training in lean and diet-induced obese mice

Exercise training is a common therapeutic approach known to antagonize the metabolic consequences of obesity. The aims of the present study were to examine 1) whether short-term, moderate-intensity exercise training alters the basal metabolite profile and 2) if 10 days of mild exercise training can correct obesity-induced shifts in metabolic spectra. After being weaned, male C57BL/6J littermates were randomly divided into two diet groups: low fat (LF) or high fat (HF). After 12 wk of dietary manipulation, HF animals were obese and hyperglycemic compared with LF animals. Mice from each group were further divided into sedentary or exercise treatments. Exercise training consisted of wheel running exercise (2 h/day, 10 days, 5.64 m/min). After exercise training, animals were rested (36 h) and fasted (6 h) before serum collection. Samples were analyzed by high-resolution one-dimensional proton NMR. Fifty high- and medium-concentration metabolites were identified. Pattern recognition algorithms and multivariate modeling were used to identify and isolate significant metabolites changing in response to HF and exercise training. The results showed that while exercise can mitigate some of the abnormal patterns in metabolic spectra induced by HF diet feeding, they cannot negate it. In fact, when the effects of diet and exercise were compared, diet was a stronger predictor and had the larger influence on the metabolic profile. External validation of models showed that diet could be correctly classified with an accuracy of 89%, whereas exercise training could be classified 73% of the time. The results demonstrate metabolomics to effectively characterize obesity-induced perturbations in metabolism and support the concept that exercise is beneficial for this condition.     

The effect of weight loss on inflammation in obese women with polycystic ovary syndrome

INTRODUCTION: The aim of the present study was to evaluate the effect of modest weight reduction on serum concentrations of tumour necrosis factor alpha (TNF-alpha), TNF soluble receptors (sTNFRs) and interleukin-6 (IL-6) in obese women with polycystic ovary syndrome (PCOS). MATERIAL AND METHODS: The study group consisted of 15 obese women with PCOS (mean age 28.5 +/- 7.7 years). Serum concentrations of TNF-alpha, sTNFRs and IL-6, insulin, FSH, LH, DHEAS, androstendione, total and free testosterone, cortisol, 17OH-progesterone, oestradiol and sex hormone binding globulin (SHBG), glucose, total cholesterol, HDL cholesterol and triglycerides were measured before treatment and after 10% weight loss. All patients were advised to follow a 1000-1200 kcal diet with a limited intake of simple carbohydrate and animal fats and to exercise regularly (30 min, 3 times a week). Body composition was measured by bioimpedance. Serum concentrations of TNF-alpha, sTNFRs and IL-6 were determined by enzyme linked immunosorbent assay (ELISA). Plasma insulin, FSH, LH, DHEAS, androstendione, total and free testosterone, cortisol, 17OH-progesterone, oestradiol and SHBG were measured by a commercial RIA. Blood glucose, total cholesterol, HDL cholesterol and triglycerides were measured by an enzymatic procedure. RESULTS: We observed no differences in serum concentrations of TNF-alpha, sTNFRs or IL-6 after treatment. CONCLUSIONS: It seems that more than a modest weight reduction is necessary to obtain a decrease in serum concentrations of proinflammatory cytokines and an improvement in ovarian function in obese women with polycystic ovary syndrome.     

The effect of moderate weight loss on echocardiographic parameters in obese female patients.

Based on the data collected by KNOLL Hungary Ltd. in Hungary in 1999, 37% of the adult population is overweight while 23% is obese. Inappropriate diet containing excess calories and physical inactivity are responsible for these statistical values. In their former studies, the authors investigated the effects of different stages of obesity on the cardiovascular system, and have verified that even moderate obesity elicits pathological geometric and functional changes in the heart. In the present study, effect of a half-year-long life-style modification program on the morphologic and functional characteristics of the heart was investigated in twenty-one obese women. Life-style modification contained a diet with reduced energy uptake (1000-1300 Cal/day) and a regular physical training of minimum 3-4 hours weekly. By the end of the sixth month the weight loss was 5.1 kg (5.9%) on an average. There was a marked reduction in cardiac dimensions measured by echocardiography, with a very slight, non-significant decrease in left ventricular internal diameter, and a marked, significant reduction in the left ventricular wall thickness. Decrease of the left ventricular muscle mass exceeded the decrease of body weight. A marked elevation was found in the E/A quotient that reflected a definite improvement in diastolic function. Results indicate that physical training programs have a favourable effect on the echocardiographic parameters, therefore the process is reversible even without a pharmacological intervention.     

Dietary GABA decreases body weight of genetically obese mice

Body weight and food intake were decreased more in lean than in genetically obese (ob/ob) mice fed a low protein diet containing GABA. Young lean and obese mice, when fed a 4.5% GABA diet, lost 30% or 20% of their initial weight over periods of 10 or 32 days, respectively. When refed the control diet both groups of mice gained weight rapidly but the obese grew more over a longer period of time. With GABA at 2 or 2.5% of the diet, respectively, lean and obese mice could be maintained at constant low weights for weeks. The obese were less sensitive than the lean mice to dietary GABA. Weights increased rapidly when a high protein diet containing GABA was fed. Hepatic GABA aminotransferase activity increased in all mice fed the high protein diet.