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Obesity results from a caloric imbalance between energy intake, absorption and expenditure. In both rodents and humans, diet-induced thermogenesis contributes to energy expenditure and involves the activation of brown adipose tissue (BAT). We hypothesize that environmental toxicants commonly used as food additives or pesticides might reduce BAT thermogenesis through suppression of uncoupling protein 1 (UCP1) and this may contribute to the development of obesity. Using a step-wise screening approach, we discover that the organophosphate insecticide chlorpyrifos suppresses UCP1 and mitochondrial respiration in BAT at concentrations as low as 1 pM. In mice housed at thermoneutrality and fed a high-fat diet, chlorpyrifos impairs BAT mitochondrial function and diet-induced thermogenesis, promoting greater obesity, non-alcoholic fatty liver disease (NAFLD) and insulin resistance. This is associated with reductions in cAMP; activation of p38MAPK and AMPK; protein kinases critical for maintaining UCP1 and mitophagy, respectively in BAT. These data indicate that the commonly used pesticide chlorpyrifos, suppresses diet-induced thermogenesis and the activation of BAT, suggesting its use may contribute to the obesity epidemic., (© 2021. The Author(s).)

Objective: Infants born to mothers with obesity have greater adiposity, ectopic fat storage, and are at increased risk for childhood obesity and metabolic disease compared with infants of normal weight mothers, though the cellular mechanisms mediating these effects are unclear., Methods: We tested the hypothesis that human, umbilical cord-derived mesenchymal stem cells (MSCs) from infants born to obese (Ob-MSC) versus normal weight (NW-MSC) mothers demonstrate altered fatty acid metabolism consistent with adult obesity. In infant MSCs undergoing myogenesis in vitro, we measured cellular lipid metabolism and AMPK activity, AMPK activation in response to cellular nutrient stress, and MSC DNA methylation and mRNA content of genes related to oxidative metabolism., Results: We found that Ob-MSCs exhibit greater lipid accumulation, lower fatty acid oxidation (FAO), and dysregulation of AMPK activity when undergoing myogenesis in vitro. Further experiments revealed a clear phenotype distinction within the Ob-MSC group where more severe MSC metabolic perturbation corresponded to greater neonatal adiposity and umbilical cord blood insulin levels. Targeted analysis of DNA methylation array revealed Ob-MSC hypermethylation in genes regulating FAO (PRKAG2, ACC2, CPT1A, SDHC) and corresponding lower mRNA content of these genes. Moreover, MSC methylation was positively correlated with infant adiposity., Conclusions: These data suggest that greater infant adiposity is associated with suppressed AMPK activity and reduced lipid oxidation in MSCs from infants born to mothers with obesity and may be an important, early marker of underlying obesity risk., (Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Intestinal dysbiosis contributes to obesity and insulin resistance, but intervening with antibiotics, prebiotics, or probiotics can be limited by specificity or sustained changes in microbial composition. Postbiotics include bacterial components such as lipopolysaccharides, which have been shown to promote insulin resistance during metabolic endotoxemia. We found that bacterial cell wall-derived muramyl dipeptide (MDP) is an insulin-sensitizing postbiotic that requires NOD2. Injecting MDP lowered adipose inflammation and reduced glucose intolerance in obese mice without causing weight loss or altering the composition of the microbiome. MDP reduced hepatic insulin resistance during obesity and low-level endotoxemia. NOD1-activating muropeptides worsened glucose tolerance. IRF4 distinguished opposing glycemic responses to different types of peptidoglycan and was required for MDP/NOD2-induced insulin sensitization and lower metabolic tissue inflammation during obesity and endotoxemia. IRF4 was dispensable for exacerbated glucose intolerance via NOD1. Mifamurtide, an MDP-based drug with orphan drug status, was an insulin sensitizer at clinically relevant doses in obese mice., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The prevalence of obesity is high resulting from chronic imbalances between energy intake and expenditure. On the expenditure side, regular exercise is associated with health benefits, including enhanced brain function. The benefits of exercise are not immediate and require persistence to be realized. Brain regions associated with health-related decisions, such as whether or not to exercise or controlling the impulse to engage in immediately rewarding activities (e.g., sedentary behavior), include reward processing and cognitive control regions. A 9 month aerobic exercise study will be conducted in 180 sedentary adults (n = 90 healthy weight [BMI = 18.5 to 26.0 kg/m(2)]; n = 90 obese [BMI = 29.0 to 41.0 kg/m(2)) to examine the brain processes underlying reward processing and impulse control that may affect adherence in a new exercise regimen. The primary aim is to use functional magnetic resonance imaging (fMRI) to examine reward processing and impulse control among participants that adhere (exercise >80% of sessions) and those that do not adhere to a nine-month exercise intervention with secondary analyses comparing sedentary obese and sedentary healthy weight participants. Our results will provide valuable information characterizing brain activation underlying reward processing and impulse control in sedentary obese and healthy weight individuals. In addition, our results may identify brain activation predictors of adherence and success in the exercise program along with measuring the effects of exercise and improved fitness on brain activation., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Unlabelled: Exercise is recommended by public health agencies for weight management; however, the role of exercise is generally considered secondary to energy restriction. Few studies exist that have verified completion of exercise, measured the energy expenditure of exercise, and prescribed exercise with equivalent energy expenditure across individuals and genders., Objective: The objective of this study was to evaluate aerobic exercise, without energy restriction, on weight loss in sedentary overweight and obese men and women., Design and Methods: This investigation was a randomized, controlled, efficacy trial in 141 overweight and obese participants (body mass index, 31.0 ± 4.6 kg/m(2) ; age 22.6 ± 3.9 years). Participants were randomized (2:2:1 ratio) to exercise at either 400 kcal/session or 600 kcal/session or to a nonexercise control. Exercise was supervised, 5 days/week, for 10 months. All participants were instructed to maintain usual ad libitum diets. Because of the efficacy design, completion of ≥90% of exercise sessions was an a priori definition of per protocol, and these participants were included in the analysis., Results: Weight loss from baseline to 10 months for the 400 and 600 kcal/session groups was 3.9 ± 4.9 kg (4.3%) and 5.2 ± 5.6 kg (5.7%), respectively, compared with weight gain for controls of 0.5 ± 3.5 kg (0.5%) (P < 0.05). Differences for weight loss from baseline to 10 months between the exercise groups and differences between men and women within groups were not statistically significant., Conclusions: Supervised exercise, with equivalent energy expenditure, results in clinically significant weight loss with no significant difference between men and women., (Copyright © 2012 The Obesity Society.)

Objective: Weight gain is an important risk factor for gastroesophageal reflux disease (GERD); however, whether weight loss can lead to resolution of GERD symptoms is not clear. Our aim was to measure the impact of weight loss on GERD symptoms., Design and Methods: In a prospective cohort study at a tertiary referral center, overweight/obese subjects (BMI 25-39.9 kg/m2) were enrolled in a structured weight loss program. Weight loss strategies included dietary modifications, increased physical activity and behavioral changes. At baseline and at 6 months, BMI and waist circumference were measured and all participants completed a validated reflux disease questionnaire., Results: A total of 332 adult subjects, mean age 46 years and 66% women were prospectively enrolled. At baseline, the mean body weight, BMI, and waist circumference were 101 (±18) kg, 35 (±5) kg/m2 and 103 (±13) cm. At 6 months, majority of the subjects (97%) lost weight (average weight loss: 13 ± 7.7 kg) and as compared with baseline, there was a significant decrease in the overall prevalence of GERD (15 vs. 37%; P < 0.01) and the mean GERD symptom score (1.8 vs. 5.5; P < 0.01). Overall, 81% of the subjects had reduction in GERD symptom scores; 65% had complete resolution and 15% had partial resolution of reflux symptoms. There was a significant correlation between % body weight loss and reduction in GERD symptom scores (r = 0.17, P < 0.05)., Conclusions: In conclusion, the overall prevalence of GERD symptoms is high (37%) in overweight and obese subjects. A structured weight loss program can lead to complete resolution of GERD symptoms in the majority of these subjects., (Copyright © 2012 The Obesity Society.)

The increased prevalence of obesity and the lack of treatment success both argue for the design and evaluation of strategies to prevent the development of overweight and obesity. To date, the role of resistance training (RT) in this regard is largely unexplored. RT may be effective for weight management as a result of increased fat-free mass (FFM), which may result in increased resting metabolic rate and increased physical activity energy expenditure. However, the literature relative to the efficacy of RT protocols recommended for healthy adults to alter the aforementioned parameters is inconsistent or inadequately evaluated. We will conduct a 9 month randomized controlled efficacy trial to compare changes in body composition (fat mass, FFM, % body fat) and energy balance in response to 2 volumes of RT (1 vs. 3 sets vs. non-exercise control) both at the completion of training (9 months) and 1 year later (body composition). This investigation will be conducted in a sample of healthy, normal and overweight, sedentary, young adult men and women; a group at high risk for development of overweight and obesity. Our results will provide information relative to the minimum volume of RT that may be associated with body weight/fat gain which may inform the development of guidelines for RT to prevent weight gain or to alter body composition., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Of 79 overweight adults with intellectual or developmental disabilities who participated in a weight loss intervention, 73 completed the 6-month diet phase. The emphasis in the intervention was consumption of high volume, low calorie foods and beverages, including meal-replacement shakes. Lower calorie frozen entrees were recommended to control portion size. A walking activity was encouraged. Participants attended monthly meetings in which a small amount of cash was exchanged for self-recorded intake and exercise records completed on picture-based forms. Average weight loss was 13.2 pounds (6.3%) of baseline weight at 6 months, with weight loss shown by 64 of the 73 individuals enrolled. Those completing a 6-month follow-up phase showed weight loss of 9.4% of baseline. Increased choice and control are discussed as possible contributors to individual success.

Background: Diets high in either dairy or calcium during moderate weight reduction both prevent loss of bone mineral density (BMD) and suppress bone turnover. The purpose of this study was to determine whether recommended dairy and calcium intakes during weight maintenance favorably affect total body BMD (TBBMD) and bone mineral content (TBBMC) in obese adults., Methods: Obese men (n=49) and women (n=64), aged 40.8+/-0.6 years, underwent 12 weeks of moderate energy restriction (approximately 1200 kcal/day) followed by 24 weeks on either a low or recommended dairy weight maintenance diet. The TBBMC and TBBMD values were measured using dual energy X-ray absorptiometry at baseline, 12, 24 and 36 weeks. Concentrations of calcium, intact parathyroid hormone (iPTH), 25OH and 1,25 (OH)(2) vitamin D in plasma were also measured. Data were analyzed using a two-factor repeated measures analysis of variance., Results: After weight loss, women exhibited a small, but statistically significant, increase in TBBMC (1.17+/-0.57%), whereas TBBMD increased in the men (1.34+/-0.28%). The iPTH concentration decreased significantly in all subjects. Despite significantly greater intakes of calcium, vitamin D and protein compared with the recommended dairy diet, there were no treatment-related differences in outcome variables after 24 weeks of weight maintenance. The TBBMC remained unchanged in women during weight stabilization; both TBBMC and TBBMD decreased in men (-1.59+/-0.51% and -0.70+/-0.25%, respectively)., Conclusions: In summary, results of this study do not provide convincing evidence that moderate weight loss through energy restriction and mild exercise reduces TBBMC in obese men and women. Similarly, a weight-maintenance diet providing the recommended daily servings of dairy does not seem to affect changes in BMC after weight loss.

Objective: Moderate weight loss alters bone turnover and reduces bone mineral density in overweight men and women. However, it is not known whether bone turnover is normalized during weight maintenance postweight loss. Thus, the objective of the present study was to examine changes in serum bone turnover markers during 9 months of weight maintenance following weight reduction on a very low-energy diet (VLED) in obese men and women., Methods: Thirty-seven men (n = 13) and women (n = 24) aged 50 +/- 9.8 years underwent 3 months of weight reduction on a VLED ( approximately 500 kcal/d) followed by 9 months on either a low-carbohydrate or low-fat weight maintenance diet ( approximately 1600 kcal/d). Concentrations of osteocalcin (OC) and C-terminal peptide of type I collagen (CTX) in serum were measured using enzyme-linked immunosorbent assay at baseline and at months 3, 6, and 12. Serum parathyroid (PTH) concentrations were measured using a chemiluminescent immunoassay at all 4 time points. Data were analyzed using a 3-factor-repeated measures analysis of variance., Results: Average weight loss was 19% +/- 3% and, during the 9-month weight maintenance period, average weight gain was approximately 3%, with no differences due to diet composition. Serum concentrations of OC and CTX significantly increased after weight reduction and remained elevated during weight maintenance. Serum PTH was reduced after weight loss. Percent changes in OC and CTX were correlated during weight maintenance (r = -0.437, p = 0.008), but not during weight loss. Percent changes in CTX and body weight were negatively correlated during weight loss (r = -0.474, p = 0.003) and maintenance (r = -0.455, p = 0.006)., Conclusions: Weight loss induced via a VLED may result in an imbalance between bone formation and resorption and accelerate remodeling. The deleterious effect of energy restriction on bone remodeling rate appears to persist during weight maintenance.

Overweight and obesity affects more than 66% of the adult population and is associated with a variety of chronic diseases. Weight reduction reduces health risks associated with chronic diseases and is therefore encouraged by major health agencies. Guidelines of the National Heart, Lung, and Blood Institute (NHLBI) encourage a 10% reduction in weight, although considerable literature indicates reduction in health risk with 3% to 5% reduction in weight. Physical activity (PA) is recommended as a component of weight management for prevention of weight gain, for weight loss, and for prevention of weight regain after weight loss. In 2001, the American College of Sports Medicine (ACSM) published a Position Stand that recommended a minimum of 150 min wk(-1) of moderate-intensity PA for overweight and obese adults to improve health; however, 200-300 min wk(-1) was recommended for long-term weight loss. More recent evidence has supported this recommendation and has indicated more PA may be necessary to prevent weight regain after weight loss. To this end, we have reexamined the evidence from 1999 to determine whether there is a level at which PA is effective for prevention of weight gain, for weight loss, and prevention of weight regain. Evidence supports moderate-intensity PA between 150 and 250 min wk(-1) to be effective to prevent weight gain. Moderate-intensity PA between 150 and 250 min wk(-1) will provide only modest weight loss. Greater amounts of PA (>250 min wk(-1)) have been associated with clinically significant weight loss. Moderate-intensity PA between 150 and 250 min wk(-1) will improve weight loss in studies that use moderate diet restriction but not severe diet restriction. Cross-sectional and prospective studies indicate that after weight loss, weight maintenance is improved with PA >250 min wk(-1). However, no evidence from well-designed randomized controlled trials exists to judge the effectiveness of PA for prevention of weight regain after weight loss. Resistance training does not enhance weight loss but may increase fat-free mass and increase loss of fat mass and is associated with reductions in health risk. Existing evidence indicates that endurance PA or resistance training without weight loss improves health risk. There is inadequate evidence to determine whether PA prevents or attenuates detrimental changes in chronic disease risk during weight gain.

Objective: To examine weight loss maintenance among previous participants of a university-based behavioral weight management program and to compare behavioral strategies and perceived barriers between successful and unsuccessful maintainers., Method: Previous program participants (n=179) completed mailed surveys assessing current weight, weight control behaviors and perceived barriers to weight loss maintenance., Results: At 14.1+/-10.8 months following completion of treatment, survey respondents were on average 12.6+/-12.6 kg, or 11.3+/-10.7%, below baseline weight; 76.5% of respondents had successfully maintained weight, defined as maintaining a weight loss of at least 5% below baseline. Compared to unsuccessful maintainers, successful maintainers reported practicing four dietary and three physical activity weight control strategies more often and experiencing five barriers to healthy eating and exercise less often. After accounting for time since treatment and maximum weight loss while in treatment, the strongest correlates of successful weight loss maintenance were frequent exercise and perceived difficulty of weight management., Conclusions: Clinically meaningful weight loss maintenance was achieved by the majority of participants. Findings support the literature indicating that physical activity is one of the strongest predictors of successful weight loss maintenance. Findings also suggest that strategies to reduce the level of perceived effort required for long-term weight control may improve maintenance outcomes.

Objective: To examine the effects of ad libitum diets with three distinct levels of fat intake for the prevention of weight gain in sedentary, normal-weight and overweight men and women., Methods and Procedures: Three hundred and five participants were randomized to one of three diets. The diets targeted <25% of energy from fat (low fat (LF)), between 28 and 32% of energy from fat (moderate fat (MF)), or >35% of energy from fat (high fat (HF)). Participants consumed two meals per day on weekdays and one meal per day on weekends in a university cafeteria over a 12-week period. Energy and nutrient content of cafeteria foods were measured by digital photography. All meals and snacks consumed outside the cafeteria were measured by dietary recall. All analysis of energy and nutrient content was completed using Nutrition Data System for Research (NDS-R) version 2005., Results: Two hundred and sixty participants completed the study. LF gained 0.1 +/- 3.1 kg, MF gained 0.8 +/- 2.5 kg, and HF gained 1.0 +/- 2.2 kg and there was no gender or age effect. Longitudinal mixed modeling indicated a significant difference among the groups in weight over time (P = 0.0366). When adjusting for total energy intake, which was a significant predictor of weight over time, the global effect for the group was eliminated. Thus, increasing weight was a function of increasing energy but not increasing percentage of fat intake., Discussion: Energy intake, but not percentage of energy from fat, appears responsible for the observed weight gain. LF diets may contribute to weight maintenance and HF diets may promote weight gain due to the influence of fat intake on total energy intake.

Acute central administration of galanin has been reported to increase fat consumption. These experiments were designed to test the hypothesis that repeated injections of galanin would elicit hyperphagia and weight gain and that this response would depend on the available diet. Male Sprague-Dawley rats were fed high (56% energy) or low (10% energy) fat diets. Galanin (300 pmol) or saline vehicle was injected into the third ventricle twice daily for 7 days and three times daily for another 6 days. On both the high-carbohydrate and high-fat diets, twice daily galanin increased daytime food intake, but there was a compensatory decrease in nighttime intake. The addition of a third, nighttime injection of galanin was ineffective in producing an increase in total 24-h intake. There was no significant increase in body weight during galanin treatment in rats eating either diet although animals eating the high-fat diet gained more weight as reflected by a significant increase in epididymal fat pad weight. Galanin treatment had no effects on serum insulin, glucose or corticosterone concentrations, measured at the end of the experiment. However, animals fed the high-fat diet had significantly higher insulin concentrations at the time of sacrifice. Although repeated central infusions of galanin reliably stimulated daytime intake of both diets, they failed to increase total daily energy intake or body weight.