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Background: MicroRNA 128-1 (miR-128-1) was recently linked to the evolutionary adaptation to famine and identified as a thrifty microRNA that controls energy expenditure, contributing to obesity and impaired glucose metabolism. Objectives: We investigated whether circulating miR-128-1-5p and its temporal changes in response to weight-loss diet interventions were related to regulating insulin resistance, adiposity, and energy expenditure in adults with overweight and obesity. We also examined whether habitual physical activity (PA) and different macronutrient intakes modified associations of changes in miR-128-1-5p with improved metabolic outcomes. Methods: This study included 495 adults who consumed weight-loss diets with different macronutrient intakes. Circulating levels of miR-128-1-5p were assessed at baseline and 6 mo after the interventions. Outcome measurements included changes in insulin resistance HOMA-IR, adiposity, and resting energy expenditure. Results: We observed significant relations between circulating miR-128-1-5p and the positive selection signals at the 2q21.3 locus assessed by the single nucleotide polymorphisms rs1446585 and rs4988235. Higher miR-128-1-5p levels were associated with greater HOMA-IR (β per 1 SD: 0.08 [SE 0.03]; P = 0.009), waist circumference (β, 1.16 [0.55]; P = 0.036), whole-body total % fat mass (β, 0.75 [0.30]; P = 0.013), and REE (β, 23 [11]; P = 0.037). In addition, higher miR-128-1-5p level was related to lower total PA index (β, -0.23 [0.07]; P = 0.001) and interacted with PA (Pinteraction < 0.05) on changes in HOMA-IR and adiposity. We found that greater increases in miR-128-1-5p levels after the interventions were associated with lesser improvements in HOMA-IR and adiposity in participants with no change/decreases in PA. Furthermore, we found that dietary fat (Pinteraction = 0.027) and protein (Pinteraction = 0.055) intakes modified relations between changes in miR-128-1-5p and REE. Conclusions: Circulating thrifty miRNA was linked to regulating body fat, insulin resistance, and energy metabolism. Temporal changes in circulating miR-128-1-5p were associated with better weight-loss outcomes during the interventions; habitual PA and dietary macronutrient intake may modify such relations. This trial was registered at clinicaltrials.gov as NCT00072995. [ABSTRACT FROM AUTHOR]

Background MicroRNAs (miRNAs) are short noncoding RNAs and important posttranscriptional regulators of gene expression. Adipose tissue is a major source of circulating miRNAs; adipose-related circulating miRNAs may regulate body fat distribution and glucose metabolism. Objectives We investigated how changes in adipose-related circulating microRNAs-99/100 (miR-99/100) in response to lifestyle interventions were associated with improved body fat distribution and reductions of diabetogenic ectopic fat depots among adults with abdominal obesity. Methods This study included adults with abdominal obesity from an 18-mo diet and physical activity intervention trial. Circulating miR-99a-5p, miR-99b-5p, and miR-100-5p were measured at baseline and 18 mo; changes in these miRNAs in response to the interventions were evaluated. The primary outcomes were changes in abdominal adipose tissue [visceral (VAT), deep subcutaneous (DSAT), and superficial subcutaneous (SSAT) adipose tissue; cm2] (n  = 144). The secondary outcomes were changes in ectopic fat accumulation in the liver (n  = 141) and pancreas (n  = 143). Results Greater decreases in miR-100-5p were associated with more reductions of VAT (β ± SE per 1-SD decrease: −9.63 ± 3.13 cm2; P  = 0.0025), DSAT (β ± SE: −5.48 ± 2.36 cm2; P  = 0.0218), SSAT (β ± SE: −4.64 ± 1.68 cm2; P  = 0.0067), and intrahepatic fat percentage (β ± SE: −1.54% ± 0.49%; P  = 0.0023) after the interventions. Similarly, participants with greater decrease in miR-99a-5p had larger 18-mo reductions of VAT (β ± SE: −10.12 ± 3.31 cm2 per 1-SD decrease; P  = 0.0027) and intrahepatic fat percentage (β ± SE: −1.28% ± 0.52%; P =  0.015). Further, decreases in circulating miR-99b-5p (β ± SE: per 1-SD decrease: −0.44% ± 0.21%; P  = 0.038) and miR-100-5p (β ± SE: −0.50% ± 0.23%; P  = 0.033) were associated with a decrease in pancreatic fat percentage, as well as improved glucose metabolism and insulin secretion at 18 mo. Conclusions Decreases in circulating miR-99-5p/100-5p expression induced by lifestyle interventions were related to improved body fat distribution and ectopic fat accumulation. Our study suggests that changes in circulating adipose-related miR-99-5p/100-5p may be linked to reducing diabetogenic fat depots in patients with abdominal obesity. This trial was registered at clinicaltrials.gov as NCT01530724. [ABSTRACT FROM AUTHOR]

Background The obesogenic environment of Western countries raises questions about its current management. Some clinical studies have explored hypnosis, although the current state of knowledge does not lead to definitive conclusions about its efficacy. Objectives We assessed the impact of Ericksonian hypnosis and self-hypnosis on disinhibition of eating in adults with obesity and high food impulsivity levels, compared with standard nutritional education. Methods From September 2014 to July 2015, adults with BMI (in kg/m2) of 30–40 and a high disinhibition score [>8 on the Three Factor Eating Questionnaire (TFEQ-51)] were included in a randomized controlled trial. The control and hypnosis groups received the same standard nutrition education in 8 workshops. In the hypnosis group, subjects had 8 sessions of hypnosis combined with training in self-hypnosis. Disinhibition (primary outcome) and other scores from the TFEQ-51 as well as anthropometric, food intake, cardiometabolic, and physical activity variables were collected at inclusion and at 8 mo. Results Of 82 randomly assigned adults, 70 participated in all sessions; 80 participated in ≥1 session and were included in the main analysis (hypnosis group, n  = 41; control group, n  = 39). After 8 mo of follow-up, disinhibition scores adjusted for baseline values were lower in the hypnosis group, with a mean between-group difference of 4.2 (95% CI: 2.8, 5.5; P  < 0.001); 67.7% of adults in the hypnosis group had normalized their disinhibition (compared with 11.1% in control; P  < 0.0001). Differences for weight (1.8 kg; 95% CI: −0.1, 3.7 kg; P  = 0.052), BMI (0.8; 95% CI: 0.1, 1.4; P  = 0.028), susceptibility to hunger score (2.2; 95% CI: 1.0, 3.3; P  < 0.001), and its 2 subscales also favored the hypnosis group. Conclusions In the management of adults with obesity and a high disinhibition score, hypnosis and self-hypnosis can significantly improve the deep mechanisms of eating behaviors and seem to have a beneficial effect on weight loss. This trial was registered at clinicaltrials.gov as NCT02292108. [ABSTRACT FROM AUTHOR]

According to a commonly held view, the obesity pandemic is caused by overconsumption of modern, highly palatable, energy-dense processed foods, exacerbated by a sedentary lifestyle. However, obesity rates remain at historic highs, despite a persistent focus on eating less and moving more, as guided by the energy balance model (EBM). This public health failure may arise from a fundamental limitation of the EBM itself. Conceptualizing obesity as a disorder of energy balance restates a principle of physics without considering the biological mechanisms that promote weight gain. An alternative paradigm, the carbohydrate-insulin model (CIM), proposes a reversal of causal direction. According to the CIM, increasing fat deposition in the body—resulting from the hormonal responses to a high-glycemic-load diet—drives positive energy balance. The CIM provides a conceptual framework with testable hypotheses for how various modifiable factors influence energy balance and fat storage. Rigorous research is needed to compare the validity of these 2 models, which have substantially different implications for obesity management, and to generate new models that best encompass the evidence. [ABSTRACT FROM AUTHOR]

Background Both obesity and hypogonadism are common in older men which could additively exacerbate age-related declines in cognitive function. However, little is known about the effects of lifestyle intervention plus testosterone replacement therapy in this population. Objectives In this secondary analysis of the LITROS (Lifestyle Intervention and Testosterone Replacement in Obese Seniors) trial, we examined whether testosterone replacement therapy would improve cognitive function when added to intensive lifestyle intervention in older men with obesity and hypogonadism. Methods Eighty-three older, obese hypogonadal men with frailty were randomly assigned to lifestyle therapy (weight management and exercise training) plus testosterone (LT + Test) or lifestyle therapy plus placebo (LT + Pbo) for 6 mo. For this report, the primary outcome was change in the global cognition composite z score. Secondary outcomes included changes in z score subcomponents: attention/information processing, memory, executive function, and language. Changes between groups were analyzed using mixed-model repeated-measures ANCOVAs following the intention-to-treat principle. Results Global cognition z score increased more in the LT + Test than in the LT + Pbo group (mean change: 0.49 compared with 0.21; between-group difference: −0.28; 95% CI: −0.45, −0.11; Cohen's d  = 0.74). Moreover, attention/information z score and memory z score increased more in the LT + Test than in the LT + Pbo group (mean change: 0.55 compared with 0.23; between-group difference: −0.32; 95% CI: −0.55, −0.09; Cohen's d  = 0.49 and mean change: 0.90 compared with 0.37; between-group difference: −0.53; 95% CI: −0.93, −0.13; Cohen's d  = 1.43, respectively). Multiple regression analyses showed that changes in peak oxygen consumption, strength, total testosterone, and luteinizing hormone were independent predictors of the improvement in global cognition (R2  = 0.38; P  < 0.001). Conclusions These findings suggest that in the high-risk population of older men with obesity and hypogonadism, testosterone replacement may improve cognitive function with lifestyle behaviors controlled via lifestyle intervention therapy. This trial was registered at clinicaltrials.gov as NCT02367105. [ABSTRACT FROM AUTHOR]

Background Lifestyle interventions are the first-line treatment for obesity, but participant weight loss is typically low. Objectives We evaluated the efficacy of an alternative lifestyle intervention [Healthy Weight for Living (HWL)] compared with a modified Diabetes Prevention Program (m-DPP). HWL was based on a revised health behavior change model emphasizing hunger management and the development of healthy food preferences. m-DPP was a standard Diabetes Prevention Program implemented with counselor time matched to HWL. Participants were adult dependents of military personnel and had overweight or obesity. Methods Participants were randomly assigned to HWL (n  = 121) or m-DPP (n  = 117), delivered primarily by group videoconference with additional midweek emails. The primary outcome was 12-mo weight change. Secondary outcomes included 6-mo changes in cardiometabolic risk factors and diet. Intention-to-treat (ITT) and complete case (CC) analyses were performed using linear mixed models. Results Retention did not differ between groups (72% and 66% for HWL and m-DPP at 12 mo, respectively; P  = 0.30). Mean ± SE adjusted 12-mo weight loss in the ITT cohort was 7.46 ± 0.85 kg for HWL and 7.32 ± 0.87 kg for m-DPP (P  = 0.91); in the CC cohort, it was 7.83 ± 0.82 kg for HWL and 6.86 ± 0.88 kg for m-DPP (P  = 0.43). Thirty-eight percent of HWL and 30% of m-DPP completers achieved ≥10% weight loss (P  = 0.32). Improvements in systolic blood pressure, LDL cholesterol, triglycerides, fasting glucose, general health, sleep, and mood were similar across groups; improvements in diastolic blood pressure were greater in m-DPP. Adjusted group mean reductions in energy intake were not significantly different between groups, but HWL participants were more adherent to their dietary prescription for lower glycemic index and high fiber and protein (P  = 0.05 to <0.001 for ITT). Conclusions HWL and m-DPP showed equivalent and clinically impactful mean weight loss with cardiometabolic benefits. These results identify an alternative approach for behavioral treatment of overweight and obesity. This trial was registered at clinicaltrials.gov as NCT02348853. [ABSTRACT FROM AUTHOR]

Weight regain remains the main challenge in obesity management, and its etiology remains elusive. The aim of the present review was to revise the available evidence regarding the "Compensatory Theory," which is an explanatory model of relapse in obesity treatment, and to propose alternative mechanisms that can contribute to weight regain. It has been proposed, and generally accepted as true, that when a person loses weight the body fights back, with physiological adaptations on both sides of the energy balance equation that try to bring body weight back to its original state: this is the Compensatory Theory. This theory proposes that the increased orexigenic drive to eat and the reduced energy expenditure that follow weight loss are the main drivers of relapse. However, evidence showing a link between these physiological adaptations to weight loss and weight regain is lacking. Here, we propose that the physiological adaptations to weight loss, both at the level of the homeostatic appetite control system and energy expenditure, are in fact a normalization to a lower body weight and not drivers of weight regain. In light of this we explore other potential mechanisms, both physiological and behavioral, that can contribute to the high incidence of relapse in obesity management. More research is needed to clearly ascertain whether the changes in energy expenditure and homeostatic appetite markers seen in reduced-obese individuals are a compensatory mechanism that drives relapse or a normalization towards a lower body weight, and to explore alternative hypotheses that explain relapse in obesity management. [ABSTRACT FROM AUTHOR]

Background Intermittent fasting (IF) and Paleolithic (Paleo) diets produce weight loss in controlled trials, but minimal evidence exists regarding long-term efficacy under free-living conditions without intense dietetic support. Objectives This exploratory, observational analysis examined adherence, dietary intake, weight loss, and metabolic outcomes in overweight adults who could choose to follow Mediterranean, IF, or Paleo diets, and standard exercise or high-intensity interval training (HIIT) programs, as part of a 12-mo randomized controlled trial investigating how different monitoring strategies influenced weight loss (control, daily self-weighing, hunger training, diet/exercise app, brief support). Methods A total of 250 overweight [BMI (in kg/m2) ≥27] healthy adults attended an individualized dietary education session (30 min) relevant to their self-selected diet. Dietary intake (3-d weighed diet records), weight, body composition, blood pressure, physical activity (0, 6, and 12 mo), and blood indexes (0 and 12 mo) were assessed. Mean (95% CI) changes from baseline were estimated using regression models. No correction was made for multiple tests. Results Although 54.4% chose IF, 27.2% Mediterranean, and 18.4% Paleo diets originally, only 54% (IF), 57% (Mediterranean), and 35% (Paleo) participants were still following their chosen diet at 12 mo (self-reported). At 12 mo, weight loss was −4.0 kg (95% CI: −5.1, −2.8 kg) in IF, −2.8 kg (−4.4, −1.2 kg) in Mediterranean, and −1.8 kg (−4.0, 0.5 kg) in Paleo participants. Sensitivity analyses showed that, due to substantial dropout, these may be overestimated by ≤1.2 kg, whereas diet adherence increased mean weight loss by 1.1, 1.8, and 0.3 kg, respectively. Reduced systolic blood pressure was observed with IF (−4.9 mm Hg;  −7.2, −2.6 mm Hg) and Mediterranean (−5.9 mm Hg; −9.0, −2.7 mm Hg) diets, and reduced glycated hemoglobin with the Mediterranean diet (−0.8 mmol/mol; −1.2, −0.4 mmol/mol). However, the between-group differences in most outcomes were not significant and these comparisons may be confounded due to the nonrandomized design. Conclusions Small differences in metabolic outcomes were apparent in participants following self-selected diets without intensive ongoing dietary support, even though dietary adherence declined rapidly. However, results should be interpreted with caution given the exploratory nature of analyses. This trial was registered with the Australian New Zealand Clinical Trials Registry as ACTRN12615000010594 at https://www.anzctr.org.au. [ABSTRACT FROM AUTHOR]

Metabolically healthy obesity refers to an obesity phenotype with no or little evidence of metabolic dysfunction. Lower liver fat content and visceral adipose tissue, greater insulin sensitivity and secretion, greater cardiorespiratory fitness, and a predominantly lower body (i.e. leg) fat deposition are key physiological traits of a metabolically healthy phenotype. About 35% of all subjects with obesity are metabolically healthy. These individuals have approximately half the risk of developing type 2 diabetes and cardiovascular disease compared with metabolically unhealthy subjects with obesity, but they still have a significantly greater risk (by 50–300%) compared with metabolically healthy lean subjects. Therefore, absence of metabolic risk factors in people with obesity should not be a contraindication for weight-loss treatment. Metabolically healthy obesity needs to be treated, and this need is reinforced by the fact that this phenotype is not stable over time, as ∼50% of these subjects will cease being metabolically healthy within ∼10 y. Intervening early is therefore important. Weight loss dose-dependently decreases visceral adipose tissue and liver fat content, and it improves multiorgan insulin sensitivity and β-cell function (i.e. it beneficially affects many of the physiological traits of a metabolically healthy phenotype); however, weight loss is very difficult to maintain. This typically results in disappointment among patients and hinders adherence, which is likely critical for the limited success of most weight-loss treatments in the long term. On the other hand, using ≥1 metabolic health targets in a non-weight-loss-centered treatment paradigm that includes prudent dietary changes and increased physical activity can serve as an appropriate first goal that can help motivate patients toward the long-term goals of obesity treatment. [ABSTRACT FROM AUTHOR]

Background Exercise is recommended for weight management, yet exercise produces less weight loss than expected, which is called weight compensation. The mechanisms for weight compensation are unclear. Objective The aim of this study was to identify the mechanisms responsible for compensation. Methods In a randomized controlled trial conducted at an academic research center, adults (n  = 198) with overweight or obesity were randomized for 24 wk to a no-exercise control group or 1 of 2 supervised exercise groups: 8 kcal/kg of body weight/wk (KKW) or 20 KKW. Outcome assessment occurred at weeks 0 and 24. Energy intake, activity, and resting metabolic rate (RMR) were measured with doubly labeled water (DLW; with and without adjustments for change in RMR), armband accelerometers, and indirect calorimetry, respectively. Appetite and compensatory health beliefs were measured by self-report. Results A per-protocol analysis included 171 participants (72.5% women; mean ± SD baseline body mass index: 31.5 ± 4.7 kg/m2). Significant (P  < 0.01) compensation occurred in the 8 KKW (mean: 1.5 kg; 95% CI: 0.9, 2.2 kg) and 20 KKW (mean: 2.7 kg; 95% CI: 2.0, 3.5 kg) groups, and compensation differed significantly between the exercise groups (P  = 0.01). Energy intake by adjusted DLW increased significantly (P  < 0.05) in the 8 KKW (mean: 90.7 kcal/d; 95% CI: 35.1, 146.4 kcal/d) and 20 KKW (mean: 123.6 kcal/d; 95% CI: 64.5, 182.7 kcal/d) groups compared with control (mean: −2.3 kcal/d; 95% CI: −58.0, 53.5 kcal/d). Results were similar without DLW adjustment. RMR and physical activity (excluding structured exercise) did not differentially change among the 3 groups. Participants with higher compared with lower compensation reported increased appetite ratings and beliefs that healthy behaviors can compensate for unhealthy behaviors. Furthermore, they increased craving for sweet foods, increased sleep disturbance, and had worsening bodily pain. Conclusions Compensation resulted from increased energy intake and concomitant increases in appetite, which can be treated with dietary or pharmacological interventions. Compensation was not due to activity or metabolic changes. This trial was registered at clinicaltrials.gov as NCT01264406. [ABSTRACT FROM AUTHOR]

Background: Body fat distribution is a marker of metabolic health independent of body size. Visceral fat accumulation has been suggested to result from a decreased expandability of the subcutaneous fat depots. Furthermore, the visceral fat may be easier to mobilize than the peripheral fat. We examined whether differences in abdominal obesity at baseline influenced prospective body-weight changes. Objective: In this study we examined whether body-fat distribution at baseline was associated with long-term and short-term weight changes. Design: We included 3 observational studies (ntotal = 7271) with mean follow-up times of 5-9 y and two 8-10-wk weight loss intervention studies (ntotal = 1091). We examined the association between baseline waist circumference and weight changes in a substitution regression model, where body weight, height, and fatfree mass were fixed so that a difference in waist circumference would reflect a difference in body fat distribution alone. The results were summarized in meta-analyses. Results: In the observational studies, we found no associations between baseline waist circumference and subsequent weight change in men (β: 0.03 kg; 95% CI: -0.01, 0.08 kg; P = 0.19), but a negligible inverse association in women (β: -0.05 kg; 95% CI: -0.08, -0.01 kg; P = 0.01). There was no association between baseline waist circumference and weight loss in the intervention studies (men: β: -0.05 kg; 95% CI: -0.13, 0.03 kg; P = 0.25; women: β: -0.00 kg; 95% CI: -0.03, 0.03 kg; P = 0.84). However, in all studies, the SDs of the weight change residuals were greater, the greater the waist circumference at baseline. This trend was statistically significant in women in most studies as well as in men in 1 of the studies. Conclusions: With narrow CIs in 3 observational studies and 2 weight loss interventions, we did not find any clinically or epidemiologically relevant association between baseline abdominal obesity and weight change. However, the present study suggests that a greater baseline abdominal obesity is a marker for greater weight fluctuations. The CCHS trial was registered at www.clinical trials.gov as NCT02993172. The Health2006 trial was registered at www.clinicaltrials.gov as NCT00316667. The ORG study was conducted before trial registration was required. The NUGENOB trial was registered at www.isrctn.com as ISRCTN25867281. The DiOGenes trial was registered at www.clinicaltrials.gov as NCT00390637. [ABSTRACT FROM AUTHOR]

Background: Lifestyle change treatments for weight loss produce medically meaningful weight reductions, but lost weight is usually regained. Meal replacements (MRs) represent one avenue for improving long-term weight loss. Another, nutrition-focused approach involves having participants make specific changes in the energy density, composition, and structure of the foods in their personal food environments. Objective: Three conditions were compared: behavior therapy (BT), BT plus MRs (BT+MR), and a nutrition-focused treatment aimed at modifying the home food environment (HFE). Design: Overweight and obese individuals (n = 262) were randomly assigned to 1 of the 3 conditions. Treatment occurred in weekly groups for 6 mo and in biweekly groups for 6 mo. Assessments were conducted at baseline and at 6, 12, 18, 24, and 36 mo. Multilevel models were used to estimate weight-change trajectories for each participant and to examine the treatment group effect on long-term weight loss. Results: A multilevel analysis indicated that all 3 groups showed significant weight loss over 12 mo that was gradually regained to the 36-mo follow-up. Mean ± SD percentages of baseline weight loss at 12 mo for BT, BT+MR, and HFE were 9.41% ± 7.92%, 10.37% ± 7.77%, and 10.97% ± 7.79%, respectively. Comparable percentages at 36 mo were 4.21%±8.64%, 3.06%±6.93%, and 4.49%±7.83%. Those in the HFE condition lost more weight than those receiving BT through the 36-mo assessment (P < 0.01), as reflected in 2 treatment × time interactions. Further analyses showed that HFE produced the largest increases in cognitive restraint and that this increase largely mediated the HFE group's improved weight loss. Conclusion: The nutrition-focused intervention studied here produced modestly greater long-term weight loss than BT, an effect that was largely explainable by an unexpected boost in cognitive restraint in this condition. This study was registered at clinicaltrials.gov as NCT01065974. [ABSTRACT FROM AUTHOR]

Background: Obesity is associated with reduced activation in the left dorsolateral prefrontal cortex (DLPFC), a region of the brain that plays a key role in the support of self-regulatory aspects of eating behavior and inhibitory control. Transcranial direct current stimulation (tDCS) is a noninvasive technique used to modulate brain activity. Objectives: We tested whether repeated anodal tDCS targeted at the left DLPFC (compared with sham tDCS) has an immediate effect on eating behavior during ad libitum food intake, resulting in weight change, and whether it might influence longer-term food intake-related appetite ratings in individuals with obesity. Design: In a randomized parallel-design study combining inpatient and outpatient assessments over 31 d, 23 individuals with obesity [12 men; mean ± SD body mass index (BMI; in kg/m²): 39.3 ± 8.42] received 15 sessions of anodal (i.e., enhancing cortical activity) or sham tDCS aimed at the left DLPFC. Ad libitum food intake was assessed through the use of a vending machine paradigm and snack food taste tests (SFTTs). Appetite was evaluated with a visual analog scale (VAS). Body weight was measured. We examined the effect of short-term (i.e., 3 sessions) and long-term (i.e., 15 sessions) tDCS on these variables. Results: Relative to sham tDCS, short-term anodal tDCS did not influence ad libitum intake of food from the vending machines. Accordingly, no effect on short-term or 4-wk weight change was observed. In the anodal tDCS group, compared with the sham group, VAS ratings for hunger and the urge to eat declined significantly more (P = 0.01 and P = 0.05, respectively), and total energy intake during an SFTT was relatively lower in satiated individuals (P = 0.01), after long-term tDCS. Conclusions: Short-term anodal tDCS of the left DLPFC did not have an immediate effect on ad libitum food intake or thereby weight change, relative to sham tDCS. Hunger and snack food intake were reduced only after a longer period of anodal tDCS in individuals with obesity. [ABSTRACT FROM AUTHOR]

Background: Emerging research suggests that redistributing total protein intake from 1 high-protein meal/d to multiple moderately high-protein meals improves 24-h muscle protein synthesis. Over time, this may promote positive changes in body composition. Objective: We sought to assess the effects of within-day protein intake distribution on changes in body composition during dietary energy restriction and resistance training. Design: In a randomized parallel-design study, 41 men and women [mean ± SEM age: 35 ± 2 y; body mass index (in kg/m²): 31.5 ± 0.5] consumed an energy-restricted diet (750 kcal/d below the requirement) for 16 wk while performing resistance training 3 d/wk. Subjects consumed 90 g protein/d (1.0 ± 0.03 g ⋅ kg-1 ⋅ d-1, 125% of the Recommended Dietary Allowance, at intervention week 1) in either a skewed (10 g at breakfast, 20 g at lunch, and 60 g at dinner; n = 20) or even (30 g each at breakfast, lunch, and dinner; n = 21) distribution pattern. Body composition was measured pre- and postintervention. Results: Over time, whole-body mass (least-squares mean ± SE: -7.9 ± 0.6 kg), whole-body lean mass ( - 1.0 ± 0.2 kg), whole-body fat mass (-6.9 ± 0.5 kg), appendicular lean mass (-0.7 ± 0.1 kg), and appendicular fat mass (-2.6 ± 0.2 kg) each decreased. The midthigh muscle area (0 ± 1 cm²) did not change over time, whereas the midcalf muscle area decreased (-3 ± 1 cm²). Within-day protein distribution did not differentially affect these body-composition responses. Conclusion: The effectiveness of dietary energy restriction combined with resistance training to improve body composition is not influenced by the within-day distribution of protein when adequate total protein is consumed. This trial was registered at clinicaltrials. gov as NCT02066948. [ABSTRACT FROM AUTHOR]

Background: A formula low-energy diet (LED) reduces weight effectively in obese patients with knee osteoarthritis, but the role of LED in long-term weight-loss maintenance is unclear. Objective: We aimed to determine the effect of intermittent LED compared with daily meal replacements on weight-loss maintenance and number of knee replacements over 3 y. Design: The design was a randomized trial with participants aged >50 y who had knee osteoarthritis and a body mass index [BMI (in kg/m²)] ≥30. Participants were recruited from the osteoarthritis outpatient clinic at Copenhagen University Hospital in Frederiksberg, Denmark; they had previously completed a 68-wk lifestyle intervention trial and achieved an average weight loss of 10.5 kg (10% of initial body weight). Participants were randomly assigned to either the intermittent treatment (IN) group with LED for 5 wk every 4 mo for 3 y or to daily meal replacements of 1--2 meals for 3 y [regular (RE) group]. Attention by dietitians and the amount of formula products were similar. Primary outcomes were changes in body weight and proportion of participants receiving knee replacements. Outcomes were analyzed on the intention-to-treat-population with the use of baseline-carried-forward imputation for missing data. Results: A total of 153 participants (means ± SDs: BMI: 33.3 ± 4.6; age: 63.8 ± 6.3 y; 83% women) were recruited between June and December 2009 and randomly assigned to the IN (n = 76) or RE (n = 77) group. A total of 53 and 56 participants, respectively, completed the trial. Weight increased by 0.68 and 1.75 kg in the IN and RE groups, respectively (mean difference: -1.06 kg; 95% CI: -2.75, 0.63 kg; P = 0.22). Alloplasty rates were low and did not differ (IN group: 8 of 76 participants; RE group: 12 of 77 participants; P = 0.35). Conclusions: After a mean 10% weight-loss and 1-y maintenance, additional use of daily meal replacements or intermittent LED resulted in weight-loss maintenance for 3 y. These results challenge the commonly held assumption that weight regain in the long term is inevitable. This trial was registered at clinicaltrials.gov as NCT00938808. [ABSTRACT FROM AUTHOR]

Background: Cholecystokinin (CCK) is an important satiety factor, acting at type 1 receptors (CCK1Rs) on vagal afferent neurons; however, CCK agonists have failed clinical trials for obesity. We postulated that CCK1R function might be defective in such patients due to abnormal membrane composition, such as that observed in cholesterol gallstone disease. Objective: Due to the challenges in directly studying CCK1Rs relevant to appetite control, our goal was to develop and apply a method to determine the impact of a patient's own cellular environment on CCK stimulus-activity coupling and to determine whether CCK sensitivity correlated with the metabolic phenotype of a high-risk population. Design: Wild-type CCK1Rs were expressed on leukocytes from 112 Hispanic patients by using adenoviral transduction and 24-h culture, with quantitation of cholesterol composition and intracellular calcium responses to CCK. Results were correlated with clinical, biochemical, and morphometric characteristics. Results: Broad ranges of cellular cholesterol and CCK responsiveness were observed, with elevated cholesterol correlated with reduced CCK sensitivity. This was prominent with increasing degrees of obesity and the presence of diabetes, particularly when poorly controlled. No single standard clinical metric correlated directly with CCK responsiveness. Reduced CCK sensitivity best correlated with elevated serum triglycerides in normal-weight participants and with low HDL concentrations and elevated glycated hemoglobin in obese and diabetic patients. Conclusions: CCK responsiveness varies widely across the population, with reduced signaling in patients with obesity and diabetes. This could explain the failure of CCK agonists in previous clinical trials and supports the rationale to develop corrective modulators to reverse this defective servomechanism for appetite control. This trial was registered at www.clinicaltrials.gov as NCT03121755. [ABSTRACT FROM AUTHOR]

Background: Obesity and associated metabolic disorders are related to impairments of the intestinal barrier. Objective: We examined lactulose:mannitol (Lac:Man) permeability in obese individuals with and without liver steatosis undergoing a weight-reduction program to test whether an effective weight-loss program improves gut barrier function and whether obese patients with or without liver steatosis differ in this function. Design: Twenty-seven adult, nondiabetic individuals [mean ± SD body mass index (BMI; in kg/m²): 43.7 ± 5.2; 78% with moderate or severe liver steatosis] were included in the follow-up intervention study (n =13 by month 12). All patients reduced their weight to a mean ± SD BMI of 36.4 ± 5.1 within 12 mo. We assessed barrier functions by the oral Lac:Man and the fecal zonulin tests. Insulin resistance was assessed by the homeostatic model assessment index (HOMA), and liver steatosis by sonography and the fatty liver index (FLI). Results: The Lac:Man ratio and circulating interleukin (IL) 6 concentration decreased during intervention from 0.080 (95% CI: 0.073, 0.093) to 0.027 (95% CI: 0.024, 0.034; P < 0.001) and from 4.2 ± 1.4 to 2.8 ± 1.6 pg/mL (P < 0.01), respectively. At study start, the Lac:Man ratio was higher in patients with moderate or severe steatosis than in those without any steatosis (P < 0.001). The Lac:Man ratio tended to correlate with HOMA (p = 0.55, P = 0.052), which correlated with FLI (p = 0.75, P < 0.01). A multiple-regression analysis led to a final model explaining FLI best through BMI, waist circumference, and the Lac:Man ratio. Conclusions: Intestinal permeability is increased in obese patients with steatosis compared with obese patients without. The increased permeability fell to within the previously reported normal range after weight reduction. The data suggest that a leaky gut barrier is linked with liver steatosis and could be a new target for future steatosis therapies. [ABSTRACT FROM AUTHOR]

Background: The effect of a weight-loss intervention on the masses of lean tissues and organs in humans is not well known. Objective: We studied the effects of a diet and exercise weight-loss intervention on skeletal muscle (SM) mass and selected organs over 2 y using MRI in overweight adults with type 2 diabetes. Design: Participants were 53 women and 39 men [mean ± SD: age 58 ± 7 y; body mass index (BMI; in kg/m²) 32 ± 3] enrolled in the Look AHEAD (Action for Health in Diabetes) trial and randomly assigned to an intensive lifestyle intervention (ILI) or diabetes support and education (DSE) on whom 2 y of data were collected. MRI-derived measurements of SM, heart, liver, kidney, spleen, and pancreas were acquired. Results: Adjusted for baseline weight, height, age, sex, and ethnicity, the ILI group weighed (mean ± SE) 6.6 ± 0.7 kg less after 1 y and 5.2 ± 0.7 kg less after 2 y, whereas the DSE group did not change significantly (--0.4 ± 0.6 and --1.0 ± 0.7 kg after 1 and 2 y, respectively; P-interaction < 0.001). Total SM decreased in both groups during year 1 (-- 1.4 ± 0.2 kg; P < 0.001) with appendicular SM regained during year 2. Liver and spleen masses decreased in the ILI group (--0.12 ± 0.02 and --0.006 ± 0.003 kg, respectively) but were unchanged in the DSE group (0.00 ± 0.02 and 0.004 ± 0.003 kg, respectively). Kidney mass decreased by 0.013 ± 0.003 kg (P < 0.001) over 2 y in both groups. Conclusions: Decreases in liver (in Caucasians but not African Americans) and spleen were detected after a 6.2-kg weight reduction compared with a control group. SM and kidney mass decreased in both groups. Appendicular SM was regained during the second year whereas trunk SM was not. No evidence of a disproportionate loss of high-metabolic rate organs (heart, liver, kidney, spleen) compared with SM was found. [ABSTRACT FROM AUTHOR]

Background: The effect of intensity and duration of physical activity (PA) on weight loss has been well described. However, the effect of the frequency of weekly PA on weight loss is still unknown. Objective: The purpose of this study was to evaluate the effect of the frequency of weekly PA sessions while maintaining the same total activity time on weight loss during a 24-wk weight loss program. Design: Overweight and obese women [n = 75; body mass index (BMI; in kg/m2): 27-37; age: 18-40 y] who had a normally sedentary lifestyle were randomly allocated to 1 of 2 intervention groups: a highfrequency physical activity (HF) or a low-frequency physical activity (LF) group. The HF group included 50 min/d PA, 6 d/wk (300 min/wk). The LF group included 100 min/d PA, 3 d/wk (300 min/wk). Both groups were advised to follow the same dietary weight loss program. Results: Both groups showed a significant decrease in anthropometric measurements and significant improvements in cardiometabolic disease risk characteristics over the 24 wk of the study. Compared with the HF group, the LF group had a greater decrease in weight (mean ± SD; LF: 9.58 ± 3.77 kg; HF: 7.78 ± 2.68 kg; P = 0.028), BMI (LF: 3.62 ± 1.56; HF: 2.97 ± 1.02; P = 0.029) and waist circumference (LF: 9.36 ± 4.02 cm; HF: 7.86 ± 2.41 cm; P = 0.031). However, there were no significant differences in carbohydrate metabolism characteristics or lipid profile after the 24 wk of intervention. Conclusion: Weekly PA undertaken over fewer sessions of longer duration during the week could be more effective for weight loss than when undertaken as more frequent shorter sessions in overweight and obese women on a weight loss program. This may be helpful for those who are neither willing nor able to schedule time for PA almost every day to achieve weight loss. This trial was registered at www.irct.ir as IRCT201402157754N4. [ABSTRACT FROM AUTHOR]

Background: Weight loss from calorie restriction (CR) and/or endurance exercise training (EX) is cardioprotective. However CR and EX also have weight loss-independent benefits. Objective: We tested the hypothesis that weight loss from calorie restriction and exercise combined (CREX) improves cardiovascular disease (CVD) risk factors more so than similar weight loss from CR or EX alone. Design: Overweight, sedentary men and women (n = 52; aged 45-65 y) were randomly assigned to undergo 6-8% weight loss by using CR, EX, or CREX. Outcomes were measured before and after weight loss and included maximal oxygen consumption (VO2max), resting blood pressure, fasting plasma lipids, glucose, C-reactive protein, and arterial stiffness [carotid-femoral pulse wave velocity (PWV) and carotid augmentation index (AI)]. Values are means ± SEs. Results: Reductions in body weight (~7%) were similar in all groups. VO2max changed in proportion to the amount of exercise performed (CR, -1% ± 3%; EX, +22% ± 3%; and CREX, +11% ± 3%). None of the changes in CVD risk factors differed between groups. For all groups combined, decreases were observed for systolic and diastolic blood pressure (-5 ± 1 and -4 ± 1 mm Hg, respectively; both P < 0.0008), total cholesterol (-17 ± 4 mg/dL; P < 0.0001), non-HDL cholesterol (-16 ± 3 mg/dL; P < 0.0001), triglycerides (-18 ± 8 mg/dL; P = 0.03), and glucose (-3 ± 1 mg/dL; P = 0.0003). No changes were observed for HDL cholesterol (P = 0.30), C-reactive protein (P = 0.10), PWV(P = 0.30), or AI (P = 0.84). These changes would be expected to decrease the lifetime risk of CVD from 46% to 36%. Conclusion: Matched weight losses from CR, EX, and CREX have substantial beneficial effects on CVD risk factors. However, the effects are not additive when weight loss is matched. This trial was registered at clinicaltrials.gov as NCT00777621. [ABSTRACT FROM AUTHOR]

Background: A hypothesis exists whereby an exercise- or dietary-induced negative energy balance reduces human subcutaneous white adipose tissue (scWAT) mass through the formation of brown-like adipocyte (brite) cells. However, the validity of biomarkers of brite formation has not been robustly evaluated in humans, and clinical data that link brite formation and weight loss are sparse. Objectives: We used rosiglitazone and primary adipocytes to stringently evaluate a set of biomarkers for brite formation and determined whether the expression of biomarker genes in scWAT could explain the change in body composition in response to exercise training combined with calorie restriction in obese and overweight women (n = 79). Design: Gene expression was derived from exon DNA microarrays and preadipocytes from obesity-resistant and -sensitive mice treated with rosiglitazone to generate candidate brite biomarkers from a microarray. These biomarkers were evaluated against data derived from scWAT RNA from obese and overweight women before and after supervised exercise 5 d/wk for 16 wk combined with modest calorie restriction (~0.84 MJ/d). Results: Forty percent of commonly used brite gene biomarkers exhibited an exon or strain-specific regulation. No biomarkers were positively related to weight loss in human scWAT. Greater weight loss was significantly associated with less uncoupling protein 1 expression (P = 0.006, R² = 0.09). In a follow-up global analysis, there were 161 genes that covaried with weight loss that were linked to greater CCAAT/enhancer binding protein a activity (z = 2.0, P = 6.6 x 10-7), liver X receptor α/β agonism (z = 2.1, P = 2.8 x 10-7), and inhibition of leptin-like signaling (z = 22.6, P = 3.9 x 10-5). Conclusion: We identify a subset of robust RNA biomarkers for brite formation and show that calorie-restriction-mediated weight loss in women dynamically remodels scWAT to take on a more-white rather than a more-brown adipocyte phenotype. [ABSTRACT FROM AUTHOR]

Background: Hormonal fluctuations during the menstrual cycle influence energy intake and expenditure as well as eating preferences and behavior. Objective: We examined the effect in healthy, overweight, premenopausal women of a diet and exercise weight-loss program that was designed to target and moderate the effects of the menstrual cycle compared with the effect of simple energy restriction. Design: A total of 60 healthy, overweight, premenopausal women were included in a 6-mo weight-loss program in which each subject consumed a diet of 1600 kcal/d. Subjects were randomly assigned to either a combined diet and exercise program that was tailored to metabolic changes of the menstrual cycle (Menstralean) or to undergo simple energy restriction (control). Results: Thirty-one women (19 Menstralean and 12 control women) completed the study [mean 6 SD body mass index (in kg/m²): 32.0 6 5.2]. Both groups lost weight during the study. In an intention-to-treat analysis, the Menstralean group did not achieve a clinically significant weight loss compared with that of the control group (P = 0.61). In per-protocol analyses, a more-pronounced weight loss of 4.3 6 1.4 kg (P = 0.002) was shown in adherent Menstralean subjects than in the control group. Conclusion: A differentiated diet and exercise program that is tailored to counteract food cravings and metabolic changes throughout the menstrual cycle may increase weight loss above that achieved with a traditional diet and exercise program in women who can comply with the program. This trial was registered at clinicaltrials.gov as NCT01622114. [ABSTRACT FROM AUTHOR]

Background: Maintenance of weight loss after a diet and exercise intervention is often low. Moreover, short follow-up periods and high attrition rates often impede translation of study results to clinical practice. Objective: The present study evaluated the long-term effectiveness of a randomized, tailor-made lifestyle intervention, consisting of diet and exercise, on the health and lifestyle of overweight, middle-aged women in primary care. Design: The intervention was part of a randomized controlled trial on the prevention of knee osteoarthritis [PROOF (PRevention of knee Osteoarthritis in Overweight Females) study]. The intervention lasted 2.5 y and consisted of visits to the dietitian and participation in physical activity classes, supervised by a physiotherapist. The outcome of main interest of the present study was weight change (in kg) 6-7 y after randomization. Additionally, the intervention's effect on change in physical activity was investigated. Results: After 6 mo, weight loss was significantly higher in the intervention group (adjusted difference: 1.34 kg; 95% CI: 0.46, 2.22 kg). Over time, this difference decreased and became nonsignificant after 24 mo. Per-protocol analyses showed similar results. After 6 mo, change in physical activity was significantly higher in the intervention group (15.2%; 95% CI: 28.6%, 1.7%). Over time, this difference increased up to 29.8% (95% CI: 2.3%, 57.2%) after 6.6 y of follow-up. Per-protocol analyses showed no significant differences in change in physical activity. Conclusions: A long-lasting intervention effect on change in physical activity was found, which increased over time. For weight change, smaller differences were found, which decreased over time. In future research, greater intervention effects on weight change are expected when higher compliance rates can be reached. The present study provides important recommendations for future research. The PROOF study was registered at http://www.isrctn.com as ISRCTN42823086. [ABSTRACT FROM AUTHOR]

Background: Obesity is a risk factor for developing several diseases, and although dietary pulses (nonoil seeds of legumes such as beans, lentils, chickpeas, and dry peas) are well positioned to aid in weight control, the effects of dietary pulses on weight loss are unclear. Objective: We summarized and quantified the effects of dietary pulse consumption on body weight, waist circumference, and body fat by conducting a systematic review and meta-analysis of randomized controlled trials. Design: We searched the databases MEDLINE, Embase, CINAHL, and the Cochrane Library through 11 May 2015 for randomized controlled trials of ≥3 wk of duration that compared the effects of diets containing whole dietary pulses with those of comparator diets without a dietary pulse intervention. Study quality was assessed by means of the Heyland Methodologic Quality Score, and risk of bias was assessed with the Cochrane Risk of Bias tool. Data were pooled with the use of generic inverse-variance random-effects models. Results: Findings from 21 trials (n = 940 participants) were included in the meta-analysis. The pooled analysis showed an overall significant weight reduction of –0.34 kg (95% CI: –0.63, –0.04 kg; P = 0.03) in diets containing dietary pulses (median intake of 132 g/d or ~1 serving/d) compared with diets without a dietary pulse intervention over a median duration of 6 wk. Significant weight loss was observed in matched negative–energy-balance (weight loss) diets (P = 0.02) and in neutral–energy-balance (weightmaintaining) diets (P = 0.03), and there was low evidence of between-study heterogeneity. Findings from 6 included trials also suggested that dietary pulse consumption may reduce body fat percentage. Conclusions: The inclusion of dietary pulses in a diet may be a beneficial weight-loss strategy because it leads to a modest weight-loss effect even when diets are not intended to be calorically restricted. Future studies are needed to determine the effects of dietary pulses on long-term weight-loss sustainability. This protocol was registered at clinicaltrials.gov as NCT01594567. [ABSTRACT FROM AUTHOR]

Background: Studies have suggested that the fat mass and obesity- associated (FTO) genotype is associated with individual variability in weight loss in response to diet/lifestyle interventions, but results are inconsistent. Objective: We aimed to provide a summary of the literature evaluating the relation between the FTO genotype and weight loss in response to diet/lifestyle interventions. Design: A search of English-language articles in the PubMed and Embase databases (through 30 April 2015) was performed. Eligible studies were diet/lifestyle weight-loss intervention studies conducted in adults that reported changes in body weight or body mass index (BMI) by the FTO variant rs9939609 (or its proxy). Differences in weight loss between FTO genotypes across studies were pooled with the use of fixed-effect models. Results: A meta-analysis of 10 studies (comprising 6951 participants) that reported the results of additive genetic models showed that individuals with the FTO TA genotype and AA genotype (those with the obesity-predisposing A allele) had 0.18-kg (95% CI: 20.09-, 0.45-kg; P = 0.19; NS) and 0.44-kg (95% CI: 0.09-, 0.79-kg; P = 0.015) greater weight loss, respectively, than those with the TT genotype. A metaanalysis of 14 studies (comprising 7700 participants) that reported the results of dominant genetic models indicated a 0.20-kg (20.43-, 0.04-kg) greater weight loss in the TA/AA genotype than in the TT genotype (P = 0.10). In addition, differences in weight loss between the AA genotype and TT genotype were significant in studies with a diet intervention only, adjustment for baseline BMI or body weight, and several other subgroups. However, the relatively small number of studies limited these stratified analyses, and there was no statistically significant difference between subgroups. Conclusions: This meta-analysis suggests that individuals carrying the homozygous FTO obesity-predisposing allele may lose more weight through diet/lifestyle interventions than noncarriers. Our data provide evidence for genetic variability in response to diet/lifestyle interventions on weight loss, although clinical applications of these findings need further investigations. [ABSTRACT FROM AUTHOR]

Background: A subset of obese individuals does not exhibit metabolically unfavorable features; this group is referred to as metabolically healthy obese (MHO). Serum concentrations of polychlorinated biphenyls (PCBs), which are chemicals with endocrine-disrupting properties, have been shown to be lower in MHO than in metabolically unhealthy obese (MUO). Objective: We studied PCB serum concentrations during and after weight loss and their relation with metabolic health. Design: We determined metabolic health features (weight, blood pressure, lipids, inflammation, and glucose metabolism) and serum PCB concentrations of 27 PCBs in a cohort of 184 overweight and obese subjects. Metabolic health was evaluated with the use of the criteria of the metabolic syndrome (MetS) [metabolic syndrome according to Adult Treatment Panel III criteria present (MetS+) or metabolic syndrome according to Adult Treatment Panel III criteria absent (MetS?)] or with extended criteria with inflammation and insulin resistance taken into account (MUO compared with MHO). Participants were treated with lifestyle counseling or bariatric surgery. A metabolic and toxicological re-evaluation was performed after 6 and 12 mo. Results: At baseline, serum ΣPCB concentrations were significantly higher in MUO than in MHO (ΣPCBs: 138 ±105 compared with 365 ± 481 ng/g lipid weight; P = 0.01) but not in MetS+ compared with MetS? subjects. No difference was detected in the percentage increase in PCB serum concentrations in MetS+ compared with MetS? subjects (median: 58% compared with 43% and 31% compared with 69% at 6 and 12 mo, respectively). The comparison of persistent with resolved MetS and MUO did not reveal any difference in ΣPCB concentration increments (median: 49% compared with 58% at 12 mo for MUO; P > 0.05). In a regression model with age, smoking, and body mass index corrected for, PCB serum concentrations at baseline were not predictive of the persistence or resolution of a metabolically unfavorable state. Conclusion: Our study indicates that the increment in serum concentrations of PCBs does not differ according to metabolic health and does not seem to influence the beneficial metabolic health effects of weight loss. [ABSTRACT FROM AUTHOR]

Background: A dietary protein intake higher than the Recommended Dietary Allowance during an energy deficit helps to preserve lean body mass (LBM), particularly when combined with exercise. Objective: The purpose of this study was to conduct a proof-of-principle trial to test whether manipulation of dietary protein intake during a marked energy deficit in addition to intense exercise training would affect changes in body composition. Design: We used a single-blind, randomized, parallel-group prospective trial. During a 4-wk period, we provided hypoenergetic (w40% reduction compared with requirements) diets providing 33 ± 1 kcal/ kg LBM to young men who were randomly assigned (n = 20/group) to consume either a lower-protein (1.2 g ⋅ kg-1 ⋅ d-1) control diet (CON) or a higher-protein (2.4 g ⋅ kg-1 ⋅ d-1) diet (PRO). All subjects performed resistance exercise training combined with high-intensity interval training for ± d/wk. A 4-compartment model assessment of body composition was made pre- and postintervention. Results: As a result of the intervention, LBM increased (P < 0.05) in the PRO group (1.2 ± 1.0 kg) and to a greater extent (P < 0.05) compared with the CON group (0.1 ± 1.0 kg). The PRO group had a greater loss of fat mass than did the CON group (PRO: 24.8 61.6 kg; CON: 23.5 ± 1.4kg; P < 0.05). All measures of exercise performance improved similarly in the PRO and CON groups as a result of the intervention with no effect of protein supplementation. Changes in serum cortisol during the intervention were associated with changes in body fat (r = 0.39, P = 0.01) and LBM (r = 20.34, P = 0.03). Conclusions: Our results showed that, during a marked energy deficit, consumption of a diet containing 2.4 g protein ⋅ kg-1 ⋅ d-1 was more effective than consumption of a diet containing 1.2 g protein ⋅ kg-1 ⋅ d-1 in promoting increases in LBM and losses of fat mass when combined with a high volume of resistance and anaerobic exercise. Changes in serum cortisol were associated with changes in body fat and LBM, but did not explain much variance in either measure. This trial was registered at clinicaltrials.gov as NCT01776359. [ABSTRACT FROM AUTHOR]

Background: Circulating amino acids, such as branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs), have been associated with diabetes risk; however, little is known about how a long-term dietary intervention for weight loss affects circulating amino acids. Objectives: We examined the effects of weight-loss diets on long-term changes in plasma amino acids and the associations of these changes with weight loss and the improvement of insulin resistance. Design: We repeatedly measured plasma amino acid profiles over 2 y in overweight or obese participants from 2 randomized, dietary intervention, weight-loss trials [774 subjects from the POUNDS LOST (Preventing Overweight Using Novel Dietary Strategies Trial) and 318 subjects from the DIRECT (Dietary Intervention Randomized Controlled Trial)]. Results: Intervention diets consistently lowered most of the amino acid concentrations, including BCAAs and AAAs, in both trials. In the POUNDS LOST, average-protein diets (15% of daily energy) showed stronger effects than did high-protein diets (25% of daily energy) on reducing concentrations of the diabetes-associated BCAA valine at 6 mo independent of the weight change. In both trials, weight loss was directly related to the concurrent reduction of the BCAAs leucine and isoleucine, the AAAs tyrosine and phenylalanine, and 4 other amino acids. For example, per kilogram of weight loss, there was a 0.04-SD decrease in log tyrosine (w0.6 mmol/L) in both trials. In addition, we showed that reductions in alanine and the AAA tyrosine were significantly related to improved insulin resistance (measured with the use of the homeostasis model assessment of insulin resistance), independent of weight loss, in both trials (both P < 0.05). For example, per 1-SD decrease in log tyrosine (~ 17 µmol/L), there was a 0.04-SD (~3%) improvement in insulin resistance in the POUNDS LOST and a 0.13-SD (~ 8%) improvement in insulin resistance in the DIRECT. Conclusion: Our findings underscore the potential importance of dietary interventions in improving amino acid profiles (i.e., reducing diabetes risk-enhancing amino acid concentrations) along with and beyond weight loss. The POUNDS LOST and the DIRECT were registered at clinicaltrials.gov as NCT00072995 and NCT00160108, respectively. [ABSTRACT FROM AUTHOR]

Background: Despite evidence for the beneficial effects of probiotics and low-fat dairy products, to our knowledge, no study has compared the beneficial effect on weight loss of consuming a probiotic yogurt (PY) compared with a standard low-fat yogurt (LF) during a hypoenergetic program. Objective: We compared the effect of the PY with LF yogurt consumption on body weight and cardiometabolic risk factors in women during a weight-loss program. Design: Overweight and obese women [body mass index (in kg/m²): 27-40; age: 18-50 y) who usually consumed standard LFs were asked to consume either PY or LF every day with their main meals for 12 wk while following a weight-loss program. Results: A total of 89 participants were randomly assigned to one of the 2 intervention groups. Baseline variables were not significantly different between groups. A statistically significant reduction in anthropometric measurements and significant improvements in cardiometabolic risk characteristics were observed over the 12 wk in both groups. However, no significant differences in weight loss and anthropometric measurements were seen between groups after the intervention. Compared with the LF group, the PY group had a greater (mean ± SD) decrease in total cholesterol (PY = -0.36 ± 0.10 mmol/L, LF = --0.31 ± 0.10 mmol/L; P = 0.024), low-density lipoprotein cholesterol (PY = -0.35 ± 0.10 mmol/L, LF = -0.31 ± 0.11 mmol/L; P = 0.018), homeostasis model assessment of insulin resistance (PY = -0.55 ± 0.32, LF = -0.42 ± 0.20; P = 0.002), 2-h postprandial glucose (PY = -0.61 ± 0.24 mmol/L, LF = -0.44 ± 0.19 mmol/L; P < 0.001), and fasting insulin concentration (PY = -1.76 ± 1.01 mU/mL, LF = -1.32 ± 0.62 mU/mL; P = 0.002), as secondary endpoints after the study. No significant differences were found for fasting plasma glucose, high-density lipoprotein cholesterol, or triglycerides within both groups after the 12 wk. Conclusion: Consumption of PY compared with LF with main meals showed no significant effects on weight loss. However, it may have positive effects on lipid profiles and insulin sensitivity during a weight-loss program. This trial was registered at http:// www.irct.ir/ as IRCT201402177754N8. [ABSTRACT FROM AUTHOR]

A correction to the article "Hypnosis Reduces Food Impulsivity in Patients With Obesity and High Levels of Disinhibition: HYPNODIET Randomized Controlled Clinical Trial," published in June 6, 2022 issue is presented.

Background: Obese people believe that drinking diet beverages (DBs) may be a simple strategy to achieve weight loss. However, nutritionists advise drinking water when attempting to lose weight. It is unclear how important drinking water instead of DBs is during a weight-loss program. Objective: In this study, we compared the effect on weight loss of either replacing DBs with water or continuing to consume DBs in adults during a 24-wk weight-loss program. Design: Overweight and obese women [n = 89; body mass index (BMI; in kg/m²): 27-40; age: 18-50 y] who usually consumed DBs in their diet were asked to either substitute water for DBs (water group) or continue drinking DBs 5 times/wk after their lunch for 24 wk (DB group) while on a weight-loss program. Results: Sixty-two participants (71%) completed the trial (32 in the DB group, 30 in the water group). Baseline variables were not statistically significantly different between groups. A statistically significant reduction in anthropometric measurements and statistically significant improvements in cardiometabolic risk characteristics were observed over 24 wk in both groups. Compared with the DB group, the water group had a greater decrease in weight (mean ± SD: water: 28.8 ± 1.9 kg; DBs: 27.6 ± 2.1 kg; P = 0.015, time 3 group), fasting insulin (mean ± SD: water: 22.84 ± 0.77 mU/L; DBs: 21.78 ± 1.25 mU/L, P < 0.001), homeostasis model assessment of insulin resistance (mean ± SD: water: 20.097 ± 0.049; DBs: 20.057 ± 0.042, P < 0.001), and 2-h postprandial glucose (mean ± SD: water: 21.02 ± 0.25 mmol/L; DBs: 20.72 ± 0.27 mmol/L; P < 0.001) over the 24 wk. However, there was no significant time 3 group interaction for waist circumference, fasting plasma glucose, and lipid profiles within both groups over 24 wk. Conclusions: Replacement of DBs with water after the main meal may lead to greater weight reduction during a weight-loss program. It may also offer clinical benefits to improve insulin resistance. This trial was registered at www.irct.ir/ as IRCT201402177754N5. [ABSTRACT FROM AUTHOR]

BACKGROUND: Resistance training (RT) improves muscle strength and overall physical function in older adults. RT may be particularly important in the obese elderly who have compromised muscle function. Whether caloric restriction (CR) acts synergistically with RT to enhance function is unknown. OBJECTIVE: As the primary goal of the Improving Muscle for Functional Independence Trial (I'M FIT), we determined the effects of adding CR for weight loss on muscle and physical function responses to RT in older overweight and obese adults. DESIGN: I'M FIT was a 5-mo trial in 126 older (65-79 y) overweight and obese men and women who were randomly assigned to a progressive, 3-d/wk, moderate-intensity RT intervention with a weight-loss intervention (RT+CR) or without a weight-loss intervention (RT). The primary outcome was maximal knee extensor strength; secondary outcomes were muscle power and quality, overall physical function, and total body and thigh compositions. RESULTS: Body mass decreased in the RT+CR group but not in the RT group. Fat mass, percentage of fat, and all thigh fat volumes decreased in both groups, but only the RT+CR group lost lean mass. Adjusted postintervention body- and thigh-composition measures were all lower with RT+CR except intermuscular adipose tissue (IMAT). Knee strength, power, and quality and the 4-m gait speed increased similarly in both groups. Adjusted postintervention means for a 400-m walk time and self-reported disability were better with RT+CR with no group differences in other functional measures, including knee strength. Participants with a lower percentage of fat and IMAT at baseline exhibited a greater improvement in the 400-m walk and knee strength and power. CONCLUSIONS: RT improved body composition (including reducing IMAT) and muscle strength and physical function in obese elderly, but those with higher initial adiposity experienced less improvement. The addition of CR during RT improves mobility and does not compromise other functional adaptations to RT. These findings support the incorporation of RT into obesity treatments for this population regardless of whether CR is part of the treatment. This trial was registered at clinicaltrials.gov as NCT01049698. [ABSTRACT FROM AUTHOR]

Background: Weight loss (WL) negatively affects bone mineral density (BMD) in older populations and has specifically been shown in women. Objective: In this prospective controlled trial, we examined variables of bone quality and endocrine changes after intentional WL in men. Design: Thirty-eight overweight and obese [mean ± SD body mass index (in kg/m²): 31.9 ± 4.4; age: 58 ± 6 y] men were recruited to either WL through caloric restriction or weight maintenance (WM) for 6 mo. Results: There was a 27.9 ± 4.4% and +0.2 ± 1.6% change in body weight in the WL and WM groups, respectively. There was a greater increase in femoral neck and total body BMD and bone mineral content (BMC) in the WM group than in the WL group (P-interaction effect < 0.05). In contrast, there was a trend for the tibia cortical thickness and area to decrease more in the WM group than in the WL group (P ≤ 0.08). There was a decrease in the periosteal circumference in both groups over time (P < 0.01) and no statistically significant changes in trabecular bone. Circulating total, free, and bioavailable estradiol decreased in the WL group compared with the WM group, and changes were different between groups (P < 0.05). Serum total and bioavailable testosterone increased in both groups (P < 0.01). Serum 25-hydroxyvitamin D increased to a similar extent in both groups (P < 0.05). Conclusions: Moderate WL in overweight and obese men did not decrease BMD at any anatomical site or alter cortical and trabecular bone and geometry. Also, despite increased BMD at some sites when maintaining excess body weight, cortical bone showed a trend in the opposite direction. This trial was registered at clinicaltrials.gov as NCT00472745. [ABSTRACT FROM AUTHOR]

Background: Intentional weight loss in obese older adults is a risk factor for muscle loss and sarcopenia. Objective: The objective was to examine the effect of a high whey protein-, leucine-, and vitamin D-enriched supplement on muscle mass preservation during intentional weight loss in obese older adults. Design: We included 80 obese older adults in a double-blind randomized controlled trial. During a 13-wk weight loss program, all subjects followed a hypocaloric diet (-600 kcal/d) and performed resistance training 3x/wk. Subjects were randomly allocated to a high whey protein-, leucine-, and vitamin D-enriched supplement including a mix of other macro- and micronutrients (150 kcal, 21 g protein; 10x/wk, intervention group) or an isocaloric control. Primary outcome was change in appendicular muscle mass. Secondary outcomes were body composition, handgrip strength, and physical performance. Data were analyzed by using ANCOVA and mixed linear models with sex and baseline value as covariates. Results: At baseline, mean ± SD age was 63 ± 5.6 y, and body mass index (in kg/m²) was 33 ± 4.4. During the trial, protein intake was 1.11 ± 0.28 g ⋅ kg body weight-1 ⋅ d-1 in the intervention group compared with 0.85 ± 0.24 g ⋅ kg body weight-1 ⋅ d-1in the control group (P < 0.001). Both intervention and control groups decreased in body weight (-3.4 ± 3.6 kg and -2.8 ± 2.8 kg; both P < 0.001) and fat mass (-3.2 ± 3.1 kg and -2.5 ± 2.4 kg; both P < 0.001), with no differences between groups. The 13-wk change in appendicular muscle mass, however, was different in the intervention and control groups [+0.4 ± 1.2 kg and -0.5 ± 2.1 kg, respectively; β = 0.95 kg (95% CI: 0.09, 1.81); P = 0.03]. Muscle strength and function improved over time without significant differences between groups. Conclusion: A high whey protein-, leucine-, and vitamin D-enriched supplement compared with isocaloric control preserves appendicular muscle mass in obese older adults during a hypocaloric diet and resistance exercise program and might therefore reduce the risk for sarcopenia. This trial was registered at the Dutch Trial Register (http://www.trialregister.nl) as NTR2751. [ABSTRACT FROM AUTHOR]

Background: There is a need for a better understanding of the factors that influence long-term weight outcomes after bariatric surgery. Objective: We examined whether pretreatment and posttreatment levels of cognitive restraint, disinhibition, and hunger and 1-y changes in these eating behaviors predict short- and long-term weight changes after surgical and conventional treatments of severe obesity. Design: Participants were from an ongoing, matched (nonrandomized) prospective intervention trial of the Swedish Obese Subjects (SOS) study. The current analyses included 2010 obese subjects who underwent bariatric surgery and 1916 contemporaneously matched obese controls who received conventional treatment. Physical measurements (e.g., weight and height) and questionnaires (e.g., Three-Factor Eating Questionnaire) were completed before the intervention and 0.5, 1, 2, 3, 4, 6, 8, and 10 y after the start of the treatment. Structural equation modeling was used as the main analytic strategy. Results: The surgery group lost more weight and reported greater decreases in disinhibition and hunger at 1- and 10-y follow-ups (all P < 0.001 in both sexes) than the control group did. Pretreatment eating behaviors were unrelated to subsequent weight changes in surgically treated patients. However, patients who had lower levels of 6-mo and 1-y disinhibition and hunger (β = 0.13-0.29, P, 0.01 in men; β = 0.11-0.28, P < 0.001 in women) and experienced larger 1-y decreases in these behaviors (β = 0.31-0.48, P < 0.001 in men; J3 = 0.24-0.51, P < 0.001 in women) lost more weight 2, 6, and 10 y after surgery. In control patients, larger 1-y increases in cognitive restraint predicted a greater 2-y weight loss in both sexes. Conclusion: A higher tendency to eat in response to various internal and external cues shortly after surgery predicted less-successful short-and long-term weight outcomes, making postoperative susceptibility for uncontrolled eating an important indicator of targeted interventions. This trial was registered at clinicaltrials.gov as NCT01479452. Am J ClinNutr 2015; 101:16-24. [ABSTRACT FROM AUTHOR]

Background: A high catabolic rate characterizes the acute phase of critical illness. Guidelines recommend an early nutritional support, regardless of the previous nutritional status. Objective: We aimed to assess whether the nutritional status of patients, which was defined by the body mass index (BMI) at admission in an intensive care unit (ICU), affected the time of nutritional support initiation. Design: We conducted a cohort study that reported a retrospective analysis of a multicenter ICU database (OUTCOMEREA) by using data prospectively entered from January 1997 to October 2012. Patients who needed orotracheal intubation within the first 72 h and >3 d were included. Results: Data from 3257 ICU stays were analyzed. The delay before feeding was different according to BMI groups (P = 0.035). The delay was longer in obese patients [BMI (in kg/m²) ≥ 30; n = 663] than in other patients with either low weight (BMI < 20; n = 501), normal weight (BMI ≥20 and <25; n = 1135), or overweight (BMI ≥25 and <30; n = 958). The association between nutritional status and a delay in nutrition initiation was independent of potential confounding factors such as age, sex, and diabetes or other chronic diseases. In comparison with normal weight, the adjusted RR (95% CI) associated with a delayed nutrition initiation was 0.92 (0.86, 0.98) for patients with low weight, 1.00 (0.94, 1.05) for overweight patients, and 1.06 (1.00, 1.12) for obese patients (P = 0.004). Conclusions: The initiation of nutritional support was delayed in obese ICU patients. Randomized controlled trials that address consequences of early compared with delayed beginnings of nutritional support in critically ill obese patients are needed. [ABSTRACT FROM AUTHOR]

Background: The brain is crucial for the control of food intake, reward, and energy homeostasis. Objective: We hypothesized that 1) brain circuits involved in energy homeostasis and reward show different functional connectivity patterns between obese and lean individuals and 2) food intake affects functional connectivity differentially in obese and lean individuals. Therefore, we compared the connectivity of the hypothalamus, amygdala, and posterior cingulate cortex, each probing a distinct network related to energy homeostasis and reward, between obese subjects and lean subjects in the fasting state and after meal ingestion. Design: We acquired 3 Tesla resting-state functional magnetic resonance imaging scans after an overnight fast and after ingestion of a liquid mixed meal in 46 obese female participants [19 with normal glucose tolerance and 27 with type 2 diabetes mellitus (T2DM)] and 12 lean subjects. Functional connectivity of our regions of interest was assessed by using a seed-based correlation approach. Results: No significant differences between normal-glucose-tolerant and T2DM subjects were observed. In the fasting state, the total obese group had stronger hypothalamic connectivity with the medial prefrontal cortex and the dorsal striatum than did the lean subjects. The amygdala was differentially connected to the right insula in obese compared with lean subjects. Food intake dampened hypothalamic connectivity with the frontal regions in lean subjects, whereas these connections were barely affected in obese subjects. Conclusions: Our results indicate that functional connectivity in several brain networks, particularly the homeostatic and cognitive control network and the reward network, was different between obese and lean subjects. In the fasting state, obesity appears to be associated with stronger functional connectivity between brain areas involved in cognitive control, motivation, and reward, whereas these connections are largely unaffected by food intake in obese compared with lean subjects. This trial was registered at clinicaltrials.gov as NCT01167959. [ABSTRACT FROM AUTHOR]

Background: Obesity impairs cognition and health-related quality of life (HRQOL) in older adults; however, the appropriate treatment of obese older adults remains controversial. Objective: The objective was to determine the independent and combined effects of weight loss and exercise on cognition, mood, and HRQOL in obese older adults. Design: One hundred seven frail, obese older adults were randomly assigned to a control, weight-management (diet), exercise, or weight-management-plus-exercise (diet-exercise) group for 1 y. In this secondary analysis, main outcomes were Modified Mini-Mental State Examination (3MS) and total Impact of Weight on Quality of Life-Lite (IWQOL) scores. Other outcomes included Word Fluency Test, Trail Making Test Parts A and B, and Geriatric Depression Scale (GDS) scores. Results: Scores on the 3MS improved more in the diet (mean±SE: 1.7±0.4), exercise (2.8±0.4), and diet-exercise (2.9±0.4) groups than in the control group (0.1±0.4) (between-group P = 0.0001-0.04); scores in the diet-exercise group improved more than in the diet group but not more than in the exercise group. Scores on the Word Fluency Test improved more in the exercise (4.1±0.8) and diet-exercise (4.2±0.7) groups than in the control group (20.8 ± 0.8; both P = 0.001). For the Trail Making Test Part A, scores in the diet-exercise group (-11.8±1.9) improved more than in the control group (-0.8±1.9) (P = 0.001); a similar finding was observed for the Trail Making Test Part B. Scores on the IWQOL improved more in the diet (7.6±1.6), exercise (10.1±1.6), and diet-exercise (14.0±1.4) groups than in the control group (0.3±1.6) (P = 0.0001-0.03); scores in the diet-exercise group improved more than in the diet group but not more than in the exercise group. In the diet-exercise group, peak oxygen consumption and strength changes were independent predictors of 3MS changes; weight and strength changes were independent predictors of IWQOL changes. GDS scores did not change. Conclusions: Weight loss and exercise each improve cognition and HRQOL, but their combination may provide benefits similar to exercise alone. These findings could inform practice guidelines with regard to optimal treatment strategies for obese older adults. [ABSTRACT FROM AUTHOR]

Background: A common obesity-risk variant rs9939609 in the fat mass- and obesity-associated (FTO) gene was recently shown to affect appetite, and the gene is sensitive to the regulation of amino acids. Objective: We examined the interaction between FTO genotype and protein intake on the long-term changes in appetite in a randomized controlled trial. Design: We genotyped FTO rs9939609 in 737 overweight adults in the 2-y Preventing Overweight Using Novel Dietary Strategies trial and assessed 4 appetite-related traits including cravings, fullness, hunger, and prospective consumption. Results: We showed that dietary protein significantly modified genetic effects on changes in food cravings and appetite scores at 6 mo after adjustment for age, sex, ethnicity, baseline body mass index, weight change, and baseline value for respective outcomes (P-interaction = 0.027 and 0.048, respectively). The A allele was associated with a greater decrease in food cravings and appetite scores in participants with high-protein--diet intake (P = 0.027 and 0.047, respectively) but not in subjects in the low-protein--diet group (P = 0.384 and 0.078, respectively). The weight regain from 6 to 24 mo attenuated gene-protein interactions. Protein intakes did not modify FTO genotype effects on other appetite measures. Conclusion: Our data suggest that individuals with the FTO rs9939609 A allele might obtain more benefits in a reduction of food cravings and appetite by choosing a hypocaloric and higher-protein weight-loss diet. This trial was registered at clinicaltrials.gov as NCT00072995. [ABSTRACT FROM AUTHOR]

Background: Vitamin D deficiency is associated with obesity; whether repletion supports weight loss and changes obesity-related biomarkers is unknown. Objective: We compared 12 mo of vitamin D3 supplementation with placebo on weight, body composition, insulin, and C-reactive protein (CRP) in postmenopausal women in a weight-loss intervention. Design: A total of 218 overweight/obese women (50-75 y of age) with serum 25-hydroxyvitamin D [25(OH)D] ≥10 ng/mL but <32 ng/mL were randomly assigned to weight loss + 2000 IU oral vitamin D3/d or weight loss + daily placebo. The weight-loss intervention included a reduced-calorie diet (10% weight loss goal) and 225 min/wk of moderate-to-vigorous aerobic activity. Mean 12-mo changes in weight, body composition, serum insulin, CRP, and 25(OH)D were compared between groups (intent-to-treat) by using generalized estimating equations. Results: A total of 86% of participants completed the 12-mo measurements. The mean (95% CI) change in 25(OH)D was 13.6 (11.6, 15.4) ng/mL in the vitamin D3 arm compared with -1.3 (-2.6, -0.3) ng/mL in the placebo arm (P < 0.0001). Changes in weight [-7.1 (-8.7, -5.7) compared with -7.4 (-8.1, -5.4) kg], body mass index (in kg/m²: both -2.8), waist circumference [-4.9 (-6.7, -2.9) compared with -4.5 (-5.6, -2.6) cm], percentage body fat [-4.1 (-4.9, -2.9) compared with -3.5 (-4.5, -2.5)], trunk fat [-4.1 (-4.7, -3.0) compared with -3.7 (-4.3, -2.9) kg], insulin [-2.5 (-3.4, -1.7) compared with -2.4 (-3.3, -1.4) μU/mL], and CRP [-0.9 (-1.2, -0.6) compared with -0.79 (-0.9, -0.4) mg/mL] were similar between groups (all P > 0.05). Compared with women who achieved 25(OH)D <32 ng/mL, women randomly assigned to vitamin D who became replete (ie, 25(OH)D ≥32 ng/mL) lost more weight [-8.8 (-11.1, -6.9) compared with -5.6 (-7.2, -5.0) kg; P = 0.05], waist circumference [-6.6 (-9.3, -4.3) compared with -2.5 (-4.6, -2.0) cm; P = 0.02], and percentage body fat [-4.7 (-6.1, -3.5) compared with -2.6 (-3.9, -2.2); P = 0.04]. Among women with complete pill counts (97% adherence), the mean decrease in CRP was 1.18 mg/mL (46%) in the vitamin D arm compared with 0.46 mg/mL (25%) in the placebo arm (P = 0.03). Conclusions: Vitamin D3 supplementation during weight loss did not increase weight loss or associated factors compared with placebo; however, women who became replete experienced greater improvements. This trial was registered at clinicaltrials.gov as NCT01240213. [ABSTRACT FROM AUTHOR]

Background: Circadian rhythm has been shown to be related to glucose metabolism and risk of diabetes, probably through effects on energy balance. Recent genome-wide association studies identified variants in circadian rhythme-related genes (CRY2 and MTNR1B)associated with glucose homeostasis. Objective: We tested whether CRY2 and MTNR1B genotypes affected changes in measures of energy expenditure in response to a weight-loss diet intervention in a 2-y randomized clinical trial, the POUNDS (Preventing Overweight Using Novel Dietary Strategies) LOST Trial. Design: The variants CRY2 rs11605924 (n = 721) and MTNR1B rs10830963 (n = 722) were genotyped in overweight or obese adults who were randomly assigned to 1 of 4 weight-loss diets that differed in their proportions of macronutrients. Respiratory quotient (RQ) and resting metabolic rate (RMR) were measured. Results: By 2 y of diet intervention, the A allele of CRY2 rs11605924 was significantly associated with a greater reduction in RQ (P = 0.03) and a greater increase in RMR and RMR/kg (both P = 0.04). The G allele of MTNR1B rs10830963 was significantly associated with a greater increase in RQ (P = 0.01) but was not related to changes in RMR and RMR/kg. In addition, we found significant gene-diet fat interactions for both CRY2 (P-interaction = 0.02) and MTNR1B (P-interaction, 0.001) in relation to 2-y changes in RQ. Conclusions: Our data indicate that variants in the circadian-related genes CRY2 and MTNR1B may affect long-term changes in energy expenditure, and dietary fat intake may modify the genetic effects. This trial was registered at www.clinicaltrials.gov as NCT00072995. [ABSTRACT FROM AUTHOR]

Background: Worksites are potentially effective locations for obesity control because they provide opportunities for group intervention and social support. Studies are needed to identify effective interventions in these settings. Objective: We examined the effects of a multicomponent lifestyle intervention on weight loss and prevention of regain in 4 worksites (2 intervention and 2 control sites). Design: Overweight and obese employees (n = 133) enrolled in this pilot worksite-randomized controlled trial with a 0-6-mo weight-loss phase and a 6-12-mo structured weight-maintenance phase. The intervention combined recommendations to consume a reduced-energy, low-glycemic load, high-fiber diet with behavioral change education. Outcome measurements included changes in body weight and cardiometabolic risk factors. Results: The mean ± SEM weight loss was substantial in intervention participants, whereas control subjects gained weight (-8.0 ± 0.7 compared with +0.9 ± 0.5 kg, respectively; P < 0.001), and 89% of participants completed the weight-loss phase. Intervention effects were not significant at the 0.05 level but would have been at the 0.10 level (P = 0.08) in a mixed model in which the worksite nested within group was a random factor. There were also significant improvements in cardiometabolic risk factors in intervention compared with control subjects regarding fasting total cholesterol, glucose, systolic blood pressure, and diastolic blood pressure (P = 0.02 for each). No significant weight regain was observed in participants who enrolled in the structured weight-maintenance program (0.5 ± 0.7 kg; P = 0.65), and overweight and obese employees in intervention worksites who were not enrolled in the weight-loss program lost weight compared with subjects in control worksites (-1.3 ± 0.5 compared with +0.7 ± 0.2 kg, respectively; P = 0.02). Conclusion: Worksites can be effective for achieving clinically important reductions in body weight and improved cardiometabolic risk factors. This trial was registered at clinicaltrials.gov as NCT01470222. [ABSTRACT FROM AUTHOR]

Background: Flexibility of food reward-related brain signaling (FRS) between food and nonfood stimuli may differ between overweight and normal-weight subjects and depend on a fasted or satiated state. Objective: The objective was to assess this flexibility in response to visual food and nonfood cues. Design: Twenty normal-weight [mean ± SEM BMI (in kg/m²) = 22.7 ± 0.2; mean ± SEM age = 22.4 ± 0.4 y] and 20 overweight (BMI = 28.1 ± 0.3; age = 24.0 ± 0.7 y) participants completed 2 fMRI scans. Subjects arrived in a fasted state and consumed a breakfast consisting of 20% of subject-specific energy requirements between 2 successive scans. A block paradigm and a food > nonfood contrast was used to determine FRS. Results: An overall stimulus x condition x subject group effect was observed in the anterior cingulate cortex (ACC) (P < 0.006, F(1,38) = 9.12) and right putamen (P < 0.006, F(1,38) = 9.27). In all participants, FRS decreased from the fasted to the satiated state in the cingulate (P < 0.005, t(39) = 3.15) and right prefrontal cortex (PFC) (P < 0.006, f(39) = 3.00). In the fasted state, they showed FRS in the PFC (P < 0.004, t(39) = 3.17), left insula (P < 0.009, t(39)) = 2.95), right insula (P < 0.005, t(39) = 3.12), cingulate cortex (P < 0.004, f(39) = 3.21), and thalamus (P < 0.006, t = 2.96). In the satiated state, FRS was limited to the left insula (P < 0.005, r(39) = 3.21), right insula (P < 0.006, t(39) = 3.04), and cingulate cortex (P < 0.005, t(39) = 3.15). Regarding subject group, in the fasted state, FRS in the ACC was more pronounced in overweight than in normal-weight subjects (P < 0.005, F(1,38) = 9.71), whereas in the satiated state, FRS was less pronounced in overweight than in normal-weight subjects in the ACC (P < 0.006, F(1,38) = 9.18) and PFC (P < 0.006, F(1,38) = 8.86), which suggests lower inhibitory control in the overweight. Conclusion: FRS was higher in the overweight in the satiated state; however, when sufficiently satiated, the overweight showed decreased inhibitory control signalling, which facilitates overeating. This trial was registered in the Dutch clinical trial register as NTR2174. [ABSTRACT FROM AUTHOR]

Background: The apolipoprotein A5 gene (AP0A5) is a major gene that regulates lipid metabolism and is modulated by dietary factors. A novel variant rs964184 in APOA5 was identified to be associated with lipids in genome-wide association studies. Objective: We examined whether this variant modified changes in lipid concentrations in response to a 2-y weight-loss diet intervention in a randomized trial. Design: The current analyses were secondary analyses of a data set from the Pounds Lost Trial. We genotyped APOA5 rs964184 in 734 overweight or obese adults who were randomly assigned to one of 4 diets that differed in percentages of energy derived from fat, protein, and carbohydrate for 2 y. We evaluated changes in fasting serum concentrations of total cholesterol (TC), LDL cholesterol, HDL cholesterol, and triglycéride from baseline to 2 y of follow-up. Results: After a 2-y dietary intervention, we showed significant interactions between the APOA5 rs964184 polymorphism and dietary fat intake (low compared with high) in the determination of changes in TC, LDL cholesterol, and HDL cholesterol (P-interaction = 0.007, 0.017, and 0.006, respectively). In the low-fat intake group (20% of energy derived from fat), carriers of the risk alíele (G alíele) exhibited greater reductions in TC and LDL cholesterol than did noncarriers (P = 0.036 and 0.039, respectively), whereas in the high-fat diet group (40% of energy derived from fat), participants with the G alíele had a greater increase in HDL cholesterol than did participants without this alíele (P = 0.038). Conclusion: Our data showed better improvement in lipid profiles from long-term low-fat diet intake in the APOA5 rs964184 risk alíele. The Pounds Lost Trial was registered at clinicaltrials.gov as NCT00072995. [ABSTRACT FROM AUTHOR]

Background: Current evidence suggests a combined treatment of postpartum weight loss of diet and exercise. However, to our knowledge, neither their separate and interactive effects nor long-term outcomes have been evaluated. Objective: We evaluated whether a 12-wk dietary behavior modification (D) treatment to decrease energy intake, physical exercise behavior modification (E) treatment to implement moderate aerobic exercise, or combined dietary and physical exercise behavior modification (DE) treatment compared with control (usual care) (C) reduces body weight in lactating women measured at the end of treatment and at a 1-y follow-up 9 mo after treatment termination. Design: At 10-14 wk postpartum, 68 lactating Swedish women with a prepregnancy BMI (in kg/m~) of 25-35 were randomly assigned to D, E, DE, or C groups. Measurements were made at baseline, after the intervention, and again at a 1-y follow-up 9 mo later. A 2 X 2 factorial approach was used to analyze main and interaction effects of treatments. Results: Weight changes after the intervention and 1-y follow-up were -8.3 ± 4.2 and -10.2 ± 5.7 kg, respectively, in the D group; -2.4 ± 3.2 and -2.7 ± 5.9 kg, respectively, in the E group; -6.9 ± 3.0 and -7.3 ± 6.3 kg, respectively, in the DE group; and -0.8 ± 3.0 and -0.9 ± 6.6 kg, respectively, in the C group. The main effects of D treatment, but not of E treatment, on weight were significant at both times (P < 0.001). Conclusions: Dietary treatment provided clinically relevant weight loss in lactating postpartum women, which was sustained at 9 mo after treatment. The combined treatment did not yield significant weight or body-composition changes beyond those of dietary treatment alone. This trial was registered at clinicaltrials.gov as NCT01343238. Am J Clin Nutr 2012;96:698-705. [ABSTRACT FROM AUTHOR]

Background: Acute studies with alginate-based preloads suggested that these strong gelling fibers may induce increased feelings of satiety and reduce energy intakes. However, the long-term efficacy and safety of alginate supplementation on body weight regulation are lacking. Objective: The primary aim of the study was to investigate the effects in subjects of alginate supplementation in conjunction with energy restriction (-300 kcal/d) on loss of body weight and fat and, second, on metabolic risk markers in comparison with in a placebo group. Design: In a parallel, double-blind, placebo-controlled study, we randomly assigned 96 obese subjects to either an energy-restricted diet plus a placebo preload supplement or an energy-restricted diet plus an alginate-based preload supplement (15 g fiber). The preload was administered as a beverage 3 times/d before main meals for a period of 12 wk. Results: No differences in loss of body weight and fat between groups were shown in the intension-to-treat (ITT) analysis (P > 0.1). However, in the complete analysis (n = 80), we showed a greater weight loss with alginate (6.78 ± 3.67 kg) than with the placebo (5.04 ± 3.40 kg) (P = 0.03), which was mainly attributed to a reduction in the percentage of body fat (P = 0.03). In the ITT analysis, a larger decrease in systolic and diastolic blood pressure was shown in the placebo group than in the alginate group (P < 0.05). Plasma concentrations of glucose, insulin, C-reactive protein, and ghrelin, HOMA-IR, and lipid metabolism did not differ between treatment groups in the ITT analysis (P > 0.1). Conclusion: These results suggest that alginate supplementation as an adjunct to energy restriction may improve weight loss in obese subjects who complete a 12-wk dietary intervention. This trial was registered at clinical trials.gov as NCT01231178. Am J Clin Nutr 2012;96:5-13. [ABSTRACT FROM AUTHOR]

Background: Dietary variety is a factor that influences consumption but has received little attention in obesity treatment. Objective: This study examined the effect of limiting the variety of different non-nutrient-dense, energy-dense foods (NND-EDFs) (ie, chips, ice cream, cookies) on dietary intake and weight loss during an 18-mo lifestyle intervention. Design: Two hundred two adults aged 51.3 ± 9.5 y with a BMI (in kg/m2) 34.9 ± 4.3 (57.8% women, 92.2% white) were randomly assigned to 1 of 2 interventions: Lifestyle (1200-1500 kcal/d, ≤30% of energy as fat; n = 101) or Lifestyle + limited variety (LV) (limit variety of NND-EDFs, ie, 2 choices; n = 101). Both interventions involved 48 group sessions. Dietary intake, NND-EDF hedonics, NND-EDF variety in the home, and weight were assessed at 0, 6, 12, and 18 mo. Results: Intent-to-treat analyses showed that the Lifestyle+LV group consumed less variety (P < 0.01) and energy daily (P < 0.05) from NND-EDFs than did the Lifestyle group at 6, 12, and 18 mo. The Lifestyle+LV group consumed less total energy daily (P < 0.05) at 6 mo than did the Lifestyle group. The Lifestyle+LV group reported less (P < 0.05) NND-EDF variety in the home at 6 and 18 mo than did the Lifestyle group. The hedonics of one chosen NND-EDF decreased more (P < 0.05) in the Lifestyle+LV group. Despite these effects, no difference in percentage weight loss occurred at 18 mo (Lifestyle+LV: -9.9 ± 7.6%; Lifestyle: -9.6 ± 9.2%). Conclusions: Limitations in dietary variety decreased intakes in the targeted area but did not affect weight loss. Limiting variety in more areas may be needed to improve weight loss and weight-loss maintenance. This trial was registered at clinicaltrials.gov as NCT01096719. [ABSTRACT FROM AUTHOR]

Background: Obesity is a serious chronic disease. Controlled-release phentermine/topiramate (PHEN/TPM CR), as an adjunct to lifestyle modification, has previously shown significant weight loss compared with placebo in a 56-wk study in overweight and obese subjects with ≥2 weight-related comorbidities. Objective: This study evaluated the long-term efficacy and safety of PHEN/TPM CR in overweight and obese subjects with cardiometabolic disease. Design: This was a placebo-controlled, double-blind, 52-wk extension study; volunteers at selected sites continued with original randomly assigned treatment [placebo, 7.5 mg phentermine/46 mg controlled-release topiramate (7.5/46), or 15 mg phentermine/92 mg controlled-release topiramate (15/92)] to complete a total of 108 wk. All subjects participated in a lifestyle-modification program. Results: Of 866 eligible subjects, 676 (78%) elected to continue in the extension. Overall, 84.0% of subjects completed the study, with similar completion rates between treatment groups. At week 108, PHEN/TPM CR was associated with significant, sustained weight loss (intent-to-treat with last observation carried forward; P < 0.0001 compared with placebo); least-squares mean percentage changes from baseline in body weight were -1.8%, -9.3%, and -10.5% for placebo, 7.5/46, and 15/92, respectively. Significantly more PHEN/TPM CR-treated subjects at each dose achieved ≥5%, ≥10%, ≥15%, and ≥20% weight loss compared with placebo (P < 0.001). PHEN/TPM CR improved cardiovascular and metabolic variables and decreased rates of incident diabetes in comparison with placebo. PHEN/TPM CR was well tolerated over 108 wk, with reduced rates of adverse events occurring between weeks 56 and 108 compared with rates between weeks 0 and 56. Conclusion: PHEN/TPM CR in conjunction with lifestyle modification may provide a well-tolerated and effective option for the sustained treatment of obesity complicated by cardiometabolic disease. [ABSTRACT FROM AUTHOR]

The article presents a study that determines the efficacy of conjugated linoleic acid (CLA) with regard to change in fat and body mass index in children. The study included 62 prepubertal children aged six to 10 years old who were overweight or obese but otherwise healthy. It revealed that CLA supplementation can decrease body fatness in childeren who were overweight or obese.

The author discusses the adipocytes function in exercise energetics and adaptation to starvation. He mentions that the highly palatable foods' obesogenic environment with hidden sugars and fats can promote obesity and metabolic syndrome, while vegetables and fruit can counteract metabolic syndrome. He states that the integration of increased physical activity and plant-based diet to change modern lifestyles and diets hold out the greatest hope for the solution on the epidemic of obesity.