Metabolic adjustments with the development, treatment, and recurrence of obesity in obesity-prone rats

Obesity is reaching epidemic proportions and predisposes afflicted individuals to several comorbidities. For these individuals, losing weight has proven to be an easier feat than maintaining a reduced weight. In obesity-prone rats, we examined if there is a metabolic propensity to regain weight after a period of significant weight loss. Twenty-four-hour energy expenditure (EE), sleeping metabolic rate (SMR), and nonprotein respiratory quotient (NPRQ) were obtained by indirect calorimetry with urinary nitrogen analysis and normalized to fat mass (FM) and fat-free mass (FFM) acquired by dual-energy X-ray absorptiometry. Obesity-prone rats were examined after free access to a high-fat diet for 16 wk to establish the obese state. They were again examined after 2 wk of calorie restriction, which reduced body weight (14%) and FM (32%). Rats were again examined after a further 8 wk of intake-regulated weight maintenance or ad libitum feeding that led to weight regain. Metabolic data were compared with preobese and age-matched controls. Weight loss suppressed EE and SMR beyond what was expected for the change in metabolic mass. This elevated metabolic efficiency persisted throughout weight maintenance but resolved after 8 wk of regain. Adjusted NPRQ values were elevated in weight-maintained and weight-regaining rats, suggesting a preference for carbohydrate utilization. These data support the concept that weight reduction in obesity is accompanied by metabolic adjustments beyond the drive to consume calories that predispose to weight regain, and some aspects of this adjustment persist with prolonged weight maintenance and during weight regain.     

Biology's response to dieting: the impetus for weight regain

Dieting is the most common approach to losing weight for the majority of obese and overweight individuals. Restricting intake leads to weight loss in the short term, but, by itself, dieting has a relatively poor success rate for long-term weight reduction. Most obese people eventually regain the weight they have worked so hard to lose. Weight regain has emerged as one of the most significant obstacles for obesity therapeutics, undoubtedly perpetuating the epidemic of excess weight that now affects more than 60% of U.S. adults. In this review, we summarize the evidence of biology's role in the problem of weight regain. Biology's impact is first placed in context with other pressures known to affect body weight. Then, the biological adaptations to an energy-restricted, low-fat diet that are known to occur in the overweight and obese are reviewed, and an integrative picture of energy homeostasis after long-term weight reduction and during weight regain is presented. Finally, a novel model is proposed to explain the persistence of the "energy depletion" signal during the dynamic metabolic state of weight regain, when traditional adiposity signals no longer reflect stored energy in the periphery. The preponderance of evidence would suggest that the biological response to weight loss involves comprehensive, persistent, and redundant adaptations in energy homeostasis and that these adaptations underlie the high recidivism rate in obesity therapeutics. To be successful in the long term, our strategies for preventing weight regain may need to be just as comprehensive, persistent, and redundant, as the biological adaptations they are attempting to counter.     

Peripheral metabolic responses to prolonged weight reduction that promote rapid, efficient regain in obesity-prone rats

Weight regain after weight loss is the most significant impediment to long-term weight reduction. We have developed a rodent paradigm that models the process of regain after weight loss, and we have employed both prospective and cross-sectional analyses to characterize the compensatory adaptations to weight reduction that may contribute to the propensity to regain lost weight. Obese rats were fed an energy-restricted (50-60% kcal) low-fat diet that reduced body weight by 14%. This reduced weight was maintained for up to 16 wk with limited provisions of the low-fat diet. Intake restriction was then removed, and the rats were followed for 56 days as they relapsed to the obese state. Prolonged weight reduction was accompanied by 1) a persistent energy gap resulting from an increased drive to eat and a reduced expenditure of energy, 2) a higher caloric efficiency of regain that may be linked with suppressed lipid utilization early in the relapse process, 3) preferential lipid accumulation in adipose tissue accompanied by adipocyte hyperplasia, and 4) humoral adiposity signals that underestimate the level of peripheral adiposity and likely influence the neural pathways controlling energy balance. Taken together, long-term weight reduction in this rodent paradigm is accompanied by a number of interrelated compensatory adjustments in the periphery that work together to promote rapid and efficient weight regain. These metabolic adjustments to weight reduction are discussed in the context of a homeostatic feedback system that controls body weight.     

Pattern and cost of weight gain in previously obese women

Weight gain is common among postobese individuals, providing an opportunity to address the cost of weight regain on energy expenditure. We investigated the energy cost of weight regain over 1 yr in 28 women [age 39.5 +/- 1.3 (SE) yr; body mass index 24.2 +/- 0.5 kg/m(2)] with recent weight loss (>12 kg). Body composition, total energy expenditure (TEE) using doubly labeled water, resting metabolic rate (RMR), and thermic effect of a meal (TEM) were assessed at 0 and 12 mo. Metabolizable energy intake (MEI) was calculated from TEE and change in body composition. Fourteen women had a weight gain of 13.2 +/- 2.1 kg. Twelve-month cumulative excess MEI, calculated as the intake in excess of TEE at month 0, was 749 +/- 149 MJ. Of this, 462 +/- 83 MJ (62%) were stored as accrued tissue, and 287 +/- 72 MJ (38%) was increased TEE. Expressed per kilogram of body weight gain, the energy cost of weight gain was calculated to be 54.8 +/- 4.6 MJ/kg. Interestingly, weight regain time courses fell into three distinct patterns, possibly requiring varying countermeasures.     

Cardiac Parasympathetic Activity Is Increased by Weight Loss in Healthy Obese Women

Objective: We studied the effect of weight reduction on cardiac parasympathetic activity (PSA) in obese women. We also studied the relationship between the changes of PSA, resting energy expenditure (REE), and major cardiovascular risk factors. Research Methods and Procedures: Changes of cardiac vagal tone, an index of PSA, REE, and major cardiovascular risk factors, were measured in 52 healthy obese women after a 6‐month weight reduction. Ten of the women were remeasured at 12 and 24 months. Cardiac vagal tone was assessed by a vagal tone monitor and REE by indirect calorimeter. Results: Cardiac vagal tone increased significantly (p = 0.046), averaging a 9.5% weight loss in 6 months. The vagal tone increased further with weight loss during the following 6 months, and thereafter, it declined with weight regain. The increase of cardiac vagal tone correlated significantly with decreases of body weight, fat mass, waist circumference, serum insulin, and heart rate. REE adjusted for fat‐free mass and age did not change with weight loss and was not related to cardiac vagal tone at any time‐point. Discussion: Cardiac PSA activity increases with weight loss in obese women. This increase may not be maintained long‐term if body weight is regained. The rise of cardiac PSA is correlated with decreases of body fat mass, abdominal fat, serum insulin, and heart rate. Cardiac PSA is not related to REE.     

Dietary adherence during weight loss predicts weight regain

This study examined the relationship between previous dietary adherence during a low-calorie diet weight loss intervention and subsequent weight change during a 2-year follow-up for weight maintenance. One hundred and sixteen healthy, recently weight reduced (lost ~12 kg, BMI 22-25 kg/m2) premenopausal women were studied. Dietary adherence was assessed by doubly labeled water (DLW) and body composition change. Comparisons were made between the upper and lower tertiles for previous dietary adherence and subsequent weight change at 1- and 2-year follow-up. Percent weight regained was significantly lower (30.9 ± 6.7% vs. 66.7 ± 9.4%; P < 0.05) in the upper compared to the lower adherence tertile for previous weight loss dietary adherence (49.9 ± 8.8% vs. 96.8 ± 12.8% P < 0.05) at 1- and 2-year follow-up, respectively. This difference was partly explained by increases in daily activity-related energy expenditure (AEE) (+95 ± 45 kcal/day vs. -44 ± 42 kcal/day, P < 0.05) and lower daily energy intake (2,066 ± 71 kcal/day vs. 2,289 ± 62 kcal/day, P < 0.05) in the higher tertile for previous dietary adherence, compared to the lower. These findings suggest that higher adherence (i.e., higher tertile) to the previous low-calorie diet predicts lower weight regain over 2-year follow-up for weight maintenance, which is explained by lower energy intake and higher physical activity. Finally, how well an individual adheres to a low-calorie diet intervention during weight loss may be a useful tool for identifying individuals who are particularly vulnerable to subsequent weight regain.     

Effects of leptin replacement alone and with exendin-4 on food intake and weight regain in weight-reduced diet-induced obese rats

Weight loss in obese humans produces a relative leptin deficiency, which is postulated to activate potent orexigenic and energy conservation mechanisms to restrict weight loss and promote weight regain. Here we determined whether leptin replacement alone or with GLP-1 receptor agonist exendin-4 attenuates weight regain or promotes greater weight loss in weight-reduced diet-induced obese (DIO) rats. Forty percent restriction in daily intake of a high-fat diet in DIO rats for 4 wk reduced body weight by 12%, body fat by 29%, and plasma leptin by 67% and normalized leptin sensitivity. When food restriction ended, body weight, body fat, and plasma leptin increased rapidly. Daily administration of leptin [3-h intraperitoneal (ip) infusions (4 nmol·kg(-1)·h(-1))] at onset and end of dark period for 3 wk did not attenuate hyperphagia and weight regain, nor did it affect mean daily meal sizes or meal numbers. Exendin-4 (50 pmol·kg(-1)·h(-1)) infusions during the same intervals prevented postrestriction hyperphagia and weight regain by normalizing meal size. Coadministration of leptin and exendin-4 did not reduce body weight more than exendin-4 alone. Instead, leptin began to attenuate the inhibitory effects of exendin-4 on food intake, meal size, and weight regain by the end of the second week of administration. Plasma leptin in rats receiving leptin was sevenfold greater than in rats receiving vehicle and 17-fold greater than in rats receiving exendin-4. Together, these results do not support the hypothesis that leptin replacement alone or with exendin-4 attenuates weight regain or promotes greater weight loss in weight-reduced DIO rats.     

Randomised comparison of diets for maintaining obese subjects' weight after major weight loss: ad lib,low fat,high carbohydrate diet v fixed energy intake.

OBJECTIVES: To compare importance of rate of initial weight loss for long term outcome in obese patients and to compare efficacy of two different weight maintenance programmes. DESIGN: Subjects were randomised to either rapid or slow initial weight loss. Completing patients were re-randomised to one year weight maintenance programme of ad lib diet or fixed energy intake diet. Patients were followed up one year later. SETTING: University research department in Copenhagen, Denmark. SUBJECTS: 43 (41 women) obese adults (body mass index 27-40) who were otherwise healthy living in or around Copenhagen. INTERVENTIONS: 8 weeks of low energy diet (2 MJ/day) or 17 weeks of conventional diet (5 MJ/day), both supported by an anorectic compound (ephedrine 20 mg and caffeine 200 mg thrice daily); one year weight maintenance programme of ad lib, low fat, high carbohydrate diet or fixed energy intake diet (< or = 7.8 MJ/day), both with reinforcement sessions 2-3 times monthly. MAIN OUTCOME MEASURES: Mean initial weight loss and proportion of patients maintaining a weight loss of > 5 kg at follow up. RESULTS: Mean initial weight loss was 12.6 kg (95% confidence interval 10.9 to 14.3 kg) in rapid weight loss group and 12.6 (9.9 to 15.3) kg in conventional diet group. Rate of initial weight loss had no effect on weight maintenance after 6 or 12 months of weight maintenance or at follow up. After weight maintenance programme, the ad lib group had maintained 13.2 (8.1 to 18.3) kg of the initial weight loss of 13.5 (11.4 to 15.5) kg, and the fixed energy intake group had maintained 9.7 (6.1 to 13.3) kg of the initial 13.8 (11.8 to 15.7) kg weight loss (group difference 3.5 (-2.4 to 9.3) kg). Regained weight at follow up was greater in fixed energy intake group than in ad lib group (11.3 (7.1 to 15.5) kg v 5.4 (2.3 to 8.6) kg, group difference 5.9 (0.7 to 11.1) kg, P < 0.03). At follow up, 65% of ad lib group and 40% of fixed energy intake group had maintained a weight loss of > 5 kg (P < 0.07). CONCLUSION: Ad lib, low fat, high carbohydrate diet was superior to fixed energy intake for maintaining weight after a major weight loss. The rate of the initial weight loss did not influence long term outcome.     

High-volume exercise program in obese bariatric surgery patients: a randomized, controlled trial

Weight regain is a problem among many bariatric surgery patients. Whether a high-volume exercise program (HVEP), a strategy to limit weight regain, is feasible in these patients is unknown. The feasibility of an HVEP in obese post-bariatric-surgery patients was determined by randomizing 33 Roux-en-Y gastric bypass (RYGB) and gastric banding (GB) surgery patients with a mean BMI of 41 ± 6 kg/m2 to an HVEP or control group for 12 weeks. The HVEP group was instructed to expend ≥ 2,000 kcal/week in moderate-intensity exercise. All patients were counseled to limit energy intake. Treatment effect was assessed by repeated measures analysis. During the last 4 weeks of the study, 53% of the HVEP group expended ≥ 2,000 kcal/week and 82% expended ≥ 1,500 kcal/week. Step count, reported time spent and energy expended during moderate physical activity, maximal oxygen consumption relative to weight, and incremental area under the postprandial blood glucose curve were significantly improved over 12 weeks in the HVEP group compared to controls (group-by-week effect: P = 0.009-0.03). Both groups reported significant improvement in some quality-of-life scales. Changes in weight, energy and macronutrient intake, resting energy expenditure (REE), fasting lipids and glucose, and fasting and postprandial insulin concentrations were not different between the two groups. HVEP is feasible in about 50% of the patients and enhances physical fitness and reduces postprandial blood glucose in bariatric surgery patients.     

Chemical sympathectomy alters regulation of body weight during prolonged ICV leptin infusion

To assess the importance of the sympathetic nervous system in regulating body weight during prolonged leptin infusion, we evaluated food intake, body weight, and physical activity in conscious, unrestrained rats. Initial studies illustrated that prolonged intracerebroventricular (ICV) infusion of leptin enhanced substrate oxidation so that adipose tissue lipid stores were completely ablated, and muscle triglyceride and liver glycogen stores were depleted. After neonatal chemical sympathectomy, changes in weight and food intake were compared in groups of sympathectomized (SYM) and control (CON) adult animals during ICV infusion of leptin. CON animals lost 60 +/- 9 g over 10 days vs. 25 +/- 3 g in the SYM animals when food intake was matched between the two groups. Greater weight loss despite similar energy intake points to an important role of the sympathetic nervous system in stimulating energy expenditure during ICV leptin infusion by increasing the resting metabolic rate, since no differences in physical activity were observed between CON and SYM groups. In conclusion, activation of the SNS by leptin increases energy expenditure by augmenting the resting metabolic rate.     

Predictors of Long‐term Weight Maintenance

Objective: The purpose of this study was to evaluate available variables of a long‐term weight maintenance study to investigate possible factors predisposing to weight regain after a period of weight loss. Research Methods and Procedures: The Maastricht Weight Maintenance Study is an ongoing longitudinal study of healthy men and women (29 men and 62 women; 18 to 65 years of age; BMI = 30.2 ± 3.1 kg/m²). A variety of parameters were measured before and after a very‐low‐energy diet and after a follow‐up of at least 2 years. Results: Mean weight loss was 7.9 ± 3.6 kg, and percent weight regain was 113.8 ± 98.1%. Percent BMI regain was negatively associated with an increase in dietary restraint (r = ?0.47, p < 0.05). Percent weight regain was negatively correlated with baseline resting metabolic rate (r = ?0.38, p = 0.01) and baseline fat mass (r = ?0.24, p = 0.05) and positively correlated with the magnitude of change in body weight (BW) expressed as maximum amplitude of BW (r = 0.21, p < 0.05). In addition, amplitude of BW was positively correlated with the frequency of dieting (r = 0.57, p < 0.01). Discussion: The best predictors for weight maintenance after weight loss were an increase in dietary restraint during weight loss, a high baseline resting metabolic rate, a relatively high baseline fat mass favoring a fat‐free mass–sparing effect during weight loss, a rather stable BW, and a low frequency of dieting. Therefore, BW maintenance after BW loss seems to be a multifactorial issue, including mechanisms that regulate an individuals’ energy expenditure, body composition, and eating behavior in such a way that energy homeostasis is maintained.     

Exercise reduces appetite and traffics excess nutrients away from energetically efficient pathways of lipid deposition during the early stages of weight regain

The impact of regular exercise on energy balance, fuel utilization, and nutrient availability, during weight regain was studied in obese rats, which had lost 17% of their weight by a calorie-restricted, low-fat diet. Weight reduced rats were maintained for 6 wk with and without regular treadmill exercise (1 h/day, 6 days/wk, 15 m/min). In vivo tracers and indirect calorimetry were then used in combination to examine nutrient metabolism during weight maintenance (in energy balance) and during the first day of relapse when allowed to eat ad libitum (relapse). An additional group of relapsing, sedentary rats were provided just enough calories to create the same positive energy imbalance as the relapsing, exercised rats. Exercise attenuated the energy imbalance by 50%, reducing appetite and increasing energy requirements. Expenditure increased beyond the energetic cost of the exercise bout, as exercised rats expended more energy to store the same nutrient excess in sedentary rats with the matched energy imbalance. Compared with sedentary rats with the same energy imbalance, exercised rats exhibited the trafficking of dietary fat toward oxidation and away from storage in adipose tissue, as well as a higher net retention of fuel via de novo lipogenesis in adipose tissue. These metabolic changes in relapse were preceded by an increase in the skeletal muscle expression of genes involved in lipid uptake, mobilization, and oxidation. Our observations reveal a favorable shift in fuel utilization with regular exercise that increases the energetic cost of storing excess nutrients during relapse and alterations in circulating nutrients that may affect appetite. The attenuation of the biological drive to regain weight, involving both central and peripheral aspects of energy homeostasis, may explain, in part, the utility of regular exercise in preventing weight regain after weight loss.     

Roux‐en‐Y Gastric Bypass Enhances Energy Expenditure and Extends Lifespan in Diet‐induced Obese Rats

Gastrointestinal weight‐loss surgery (GIWLS) is currently the most effective treatment for severe obesity, with Roux en‐Y gastric bypass (RYGB) among the best of the available surgical options. Despite its widespread clinical use, the mechanisms by which RYGB induces its profound weight loss remain largely unknown. This procedure effects weight loss by altering the physiology of weight regulation and eating behavior rather than by simple mechanical restriction and/or malabsorption as previously thought. To study how RYGB affects the physiology of energy balance, we developed a rat model of this procedure. In this report, we demonstrate that RYGB in diet‐induced obese (DIO) rats induces a 25% weight loss, prolongs mean survival by 45%, and normalizes glucose homeostasis and lipid metabolism. RYGB induced a 19% increase in total and a 31% increase in resting energy expenditure (REE). These effects, along with a 17% decrease in food intake and a 4% decrease in nutrient absorption account for the normalization of body weight after this procedure. These effects indicate that surgery acts by altering the physiology of weight regulation and help to explain the effectiveness of RYGB in comparison to restrictive dieting and other forms of dietary and pharmacological therapies for obesity. The clinical effectiveness of RYGB and its physiological effects on body weight regulation and energy expenditure (EE) suggest that this operation provides a unique opportunity to explore the mechanisms of energy homeostasis and to identify novel therapies for obesity and related metabolic diseases.     

Effect of Regain of Body Weight on Regional Body Fat Distribution: Comparison Between Pre- and Postmenopausal Obese Women

The aim of our study was to determine if regain of body weight increases visceral fat in obese women and if regain of weight has a different effect upon pre- and postmenopausal women. Twenty obese women (11 pre- and 9 postmenopausal) underwent a very low energy diet (VLED) for 2 weeks to lose weight. They then regained body weight in spite of the recommended hypocaloric diet. No significant modifications in body fat distribution indexes were found by computed tomography between VLED and after regain of weight. No significant changes were found in metabolic variables. No interactions between menopausal status and regain of body weight were observed. In conclusion, regain of weight does not seem to cause an increase in visceral fat; both pre- and postmenopausal women showed the same body fat distribution before weight loss and after regain of weight.     

Acute Administration of Phenylpropanolamine Fails to Affect Resting Energy Expenditure in Men of Normal Weight

RUSHING, PA, SE WINDERS, SL WATSON, RC KLESGES. Acute administration of phenylpropanolamine fails to affect resting energy expenditure in men of normal weight. Studies have consistently found that dieters using over-the-counter weight control products containing phenylpropanolamine (PPA) are more successful at losing weight than those who do not. To explore the possibility that drug-induced metabolic changes contribute to weight loss associated with this compound, this study investigated the effects of PPA on resting metabolic rate in 20 healthy men of normal weight between the ages of 18 and 29. After the arrival of the subjects to the laboratory, blood pressure was taken and resting energy expenditure (REE) and respiratory quotient (RQ) were assessed for 20 minutes (Baseline) via indirect calorimetry. Half of the subjects were then given 75 mg of immediate-release PPA (administered orally via a gelatin capsule), while the other half received placebo. Immediately after drug administration, metabolic rate was measured for an additional 95 minutes (During Drug). After this assessment, blood pressure was again measured. Although significant increases in both systolic and diastolic blood pressure were observed after PPA administration, the drug had no effect on REE or RQ. These results, consistent with that previously reported in mildly overweight women, further establish that it is unlikely that drug-induced metabolic changes contribute to PPA-induced weight loss in humans.     

Estrogenic regulation of body weight in the female rat.

For a period of weeks subsequent to bilateral ovariectomy, female rats given unlimited access to food increased their food intakes and the rates at which they gained body weight; this resulted in elevated levels of body weight. Restricting ovariectomized (ovx) rats to their preoperative level of food intake (restricted diet), prevented this excessive gain in body weight. Estradiol benzoate (EB) treatments of 0.5 μg per day for 15 consecutive days partially reversed pre-occurring weight gain in obese ovx rats; this was accompanied by a reduction in food intake. In contrast, identical EB treatment for nonobese ovx rats (restricted diet) did not result in any loss of body weight or change in food intake. Oil-treated nonobese ovx rats gained a small amount of weight relative to their EB-treated counterparts, despite the similarity in their food intakes. Thus, part of the increased weight gain observed after ovariectomy may be independent of changes in food consumption, and related to removal of estrogenic influences from metabolic and behavioral processes involved in energy balance. The weight limiting actions of estradiol were far more pronounced in animals already obese or facing impending obesity than in animals in which excessive weight gain was prevented. The data also suggest that estradiol is more effective in preventing than in reversing the weight gain associated with ovariectomy, and that estrogenic influences on the body weight set point are manifested with very short latencies. These findings support earlier conclusions that estradiol does not regulate food intake directly, but secondarily controls consumption as a means of weight regulation.     

Lifestyle intervention leading to moderate weight loss normalizes postprandial triacylglycerolemia despite persisting obesity

Obesity is associated with impaired postprandial triacylglycerolemia, an independent risk factor for cardiovascular disease. Given that obesity is hard to treat, efforts should focus on treating its comorbidities. We aimed to investigate whether moderate weight loss normalizes postprandial triacylglycerol (TAG) concentrations, in the absence of the acute effects of negative energy balance. For this purpose, postprandial lipemia was investigated in eight obese but otherwise healthy, sedentary men (age: 41.3 ± 4.1 years, BMI: 36.5 ± 1.6 kg·m(-2)), once before and again after a 10% weight loss followed by ≥4 weeks of weight maintenance, and was compared with that of eight age-matched healthy lean men (BMI: 24.7 ± 0.6 kg·m(-2)). Dietary intervention consisted of reduced carbohydrate and saturated fat intake and increased monounsaturated fat intake. Obese volunteers were advised to increase physical activity using pedometers to record daily activity. Postprandial triacylglycerolemia after weight loss was reduced by 27-46% (P < 0.05), and became similar to that of lean men despite persisting obesity (BMI after weight loss: 32.9 ± 1.5 kg·m(-2)). Reduction in postprandial TAG responses was inversely correlated with the decrease in postprandial insulin sensitivity index (ISI) after weight loss (r = -0.714, P = 0.047). We conclude that moderate weight loss induced by a low-carbohydrate and saturated fat diet and a slight increase in daily physical activity normalizes postprandial triacylglycerolemia in obese men, independently of acute diet-induced negative energy balance, and possibly through enhancement of insulin action.     

Weight maintenance 2 years after participation in a weight loss program promoting low-energy density foods

Objective: Observational study designed to determine weight outcomes and associated dietary intake patterns for a sample of participants ≥1 year after completing the University of Alabama at Birmingham EatRight Weight Management Program. Research Methods and Procedures: Seventy‐four former participants (64% women) completed follow‐up visits ≥1 year after participating in EatRight, which promotes low‐energy density, high‐complex carbohydrate foods. Weight maintenance was defined as gaining <5% of body weight since completion of the EatRight program and staying below their program entry weight. Those who gained ≥5% of their body weight since completion were classified as gainers. Results: During EatRight, participants of the follow‐up study lost an average of 4.0 kg. After a mean follow‐up time of 2.2 years, the average weight change was +0.59 kg (mean BMI, 32.5 kg/m²). Seventy‐eight percent of participants gained <5% of their body weight; 46% had no weight regain or continued weight loss. Unadjusted mean intake for maintainers was 1608 kcal, whereas calorie intake for gainers was 1989 kcal. Despite eating slightly fewer calories (adjusted difference, 244; p = 0.058), maintainers ate a similar amount of food, resulting in a lower energy‐density pattern (p = 0.016) compared with those who regained ≥5% of body weight. Gainers also reported consuming larger portions of several food groups. Discussion: Our results indicate that low‐energy‐density eating habits are associated with long‐term weight maintenance. Those who maintain weight after the EatRight program consume a low‐energy‐density dietary pattern and smaller portions of food groups potentially high in energy density than those who regain weight.     

Normal vs. high‐protein weight loss diets in men: Effects on body composition and indices of metabolic syndrome

Objective:

This study assessed the effectiveness of a prescribed weight‐loss diet with 0.8 versus 1.4 g protein·kg^?1 day^?1 on changes in weight, body composition, indices of metabolic syndrome, and resting energy expenditure (REE) in overweight and obese men.

Design and Methods:

Men were randomized to groups that consumed diets containing 750 kcal day^?1 less than daily energy needs for weight maintenance with either normal protein (NP, n = 21) or higher protein (HP, n = 22) content for 12 weeks. The macronutrient distributions of the NP and HP diets were 25:60:15, and 25:50:25 percent energy from fat, carbohydrate, and protein, respectively. Assessments were made pre and post intervention. The subjects were retrospectively subgrouped into overweight and obese groups.

Results and Conclusion:

Both diet groups lost comparable body weight and fat. The HP group lost less lean body mass than the NP group (?1.9 ± 0.3 vs. ?3.0 ± 0.4 kg). The effects of protein and BMI status on lean body mass loss were additive. The reductions in total cholesterol, HDL‐C, triacylglycerol, glucose, and insulin, along with LDL‐C, total cholesterol‐to‐HDL‐C ratio, and HOMA‐IR, were not statistically different between NP and HP. Likewise, macronutrient distributions of the diet did not affect the reductions in REE, and blood pressure. In conclusion, energy restriction effectively improves multiple clinical indicators of cardiovascular health and glucose control, and consumption of a higher‐protein diet and accomplishing weight loss when overweight versus obese help men preserve lean body mass over a short period of time.

     

Effect of weight loss on the rate of muscle protein synthesis during fasted and fed conditions in obese older adults

Although weight loss ameliorates many of the metabolic abnormalities associated with obesity, there has been reluctance to prescribe weight loss in obese, older individuals because of the fear that it will cause debilitating loss of muscle mass and impair physical function. To gain insight into the mechanisms responsible for the weight loss-induced changes in muscle mass, we measured the rate of muscle protein synthesis (by using stable isotope labeled tracer methodology) during basal, postabsorptive conditions and during mixed meal ingestion in eight obese, older adults: (i) before weight loss therapy, (ii) ~3 months after starting the weight loss intervention (i.e., during the active weight loss phase), when subjects had lost ~7% of their initial body weight, and (iii) after they had lost ~10% of their body weight and maintained this new body weight for ~6 months (~12 months after starting the weight loss intervention). The basal muscle protein fractional synthesis rate (FSR) was not affected by weight loss. Mixed meal ingestion stimulated the rate of muscle protein synthesis, and the anabolic response (i.e., increase in the protein synthesis rate above basal values) was greater (P < 0.05) during negative energy balance and active weight loss at 3 months (0.033 ± 0.012%·per hour, mean ± s.e.m.) than during weight maintenance before and at 12 months of weight loss therapy (0.003 ± 0.003 and 0.008 ± 0.012%·per hour, respectively). We conclude that during dietary calorie restriction and weight loss in older adults, the rate of muscle protein synthesis is not impaired. Thus, the loss of muscle mass must be mediated predominately by adverse effects of dietary calorie restriction on muscle proteolysis.