Effects of exercise training programmes on fasting gastrointestinal appetite hormones in adults with overweight and obesity: A systematic review and meta-analysis.

A systematic review and meta-analysis was performed to determine the effect of exercise training on fasting gastrointestinal appetite hormones in adults living with overweight and obesity. For eligibility, only randomised controlled trials (duration ≥ four weeks) examining the effect of exercise training interventions were considered. This review was registered in the International Prospective Register of Systematic Reviews (CRD42020218976). The searches were performed on five databases: MEDLINE, EMBASE, Cochrane Library, Web of Science, and Scopus. The initial search identified 13204 records. Nine studies, which include sixteen exercise interventions, met the criteria for inclusion. Meta-analysis was calculated as the standardised mean difference (Cohen's d). Exercise training had no effect on fasting concentrations of total ghrelin (d: 1.06, 95% CI -0.38 to 2.50, P = 0.15), acylated ghrelin (d: 0.08, 95% CI: -0.31 to 0.47, P = 0.68) and peptide YY (PYY) (d = -0.16, 95% CI: -0.62 to 0.31, P = 0.51) compared to the control group. Analysis of body mass index (BMI) (d: -0.31, 95% CI: -0.50 to -0.12, P < 0.01) and body mass (d: -0.22, 95% CI: -0.42 to -0.03, P = 0.03) found a significant reduction after exercise compared to controls. Overall, exercise interventions did not modify fasting concentrations of total ghrelin, acylated ghrelin, and PYY in individuals with overweight or obesity, although they reduced body mass and BMI. Thus, any upregulation of appetite and energy intake in individuals with overweight and obesity participating in exercise programmes is unlikely to be related to fasting concentrations of gastrointestinal appetite hormones.

Effects of a 2-Year Primary Care Lifestyle Intervention on Cardiometabolic Risk Factors: A Cluster-Randomized Trial.

BACKGROUND: Intensive lifestyle interventions (ILIs) are the first-line approach to effectively treat obesity and manage associated cardiometabolic risk factors. Because few people have access to ILIs in academic health centers, primary care must implement similar approaches for a meaningful effect on obesity and cardiometabolic disease prevalence. To date, however, effective lifestyle-based obesity treatment in primary care is limited. We examined the effectiveness of a pragmatic ILI for weight loss delivered in primary care among a racially diverse, low-income population with obesity for improving cardiometabolic risk factors over 24 months. METHODS: The PROPEL trial (Promoting Successful Weight Loss in Primary Care in Louisiana) randomly allocated 18 clinics equally to usual care or an ILI and subsequently enrolled 803 (351 usual care, 452 ILI) adults (67% Black, 84% female) with obesity from participating clinics. The usual care group continued to receive their normal primary care. The ILI group received a 24-month high-intensity lifestyle-based obesity treatment program, embedded in the clinic setting and delivered by health coaches in weekly sessions initially and monthly sessions in months 7 through 24. RESULTS: As recently demonstrated, participants receiving the PROPEL ILI lost significantly more weight over 24 months than those receiving usual care (mean difference, -4.51% [95% CI, -5.93 to -3.10]; P<0.01). Fasting glucose decreased more in the ILI group compared with the usual care group at 12 months (mean difference, -7.1 mg/dL [95% CI, -12.0 to -2.1]; P<0.01) but not 24 months (mean difference, -0.8 mg/dL [95% CI, -6.2 to 4.6]; P=0.76). Increases in high-density lipoprotein cholesterol were greater in the ILI than in the usual care group at both time points (mean difference at 24 months, 4.6 mg/dL [95% CI, 2.9-6.3]; P<0.01). Total:high-density lipoprotein cholesterol ratio and metabolic syndrome severity (z score) decreased more in the ILI group than in the usual care group at both time points, with significant mean differences of the change of -0.31 (95% CI, -0.47 to -0.14; P<0.01) and -0.21 (95% CI, -0.36 to -0.06; P=0.01) at 24 months, respectively. Changes in total cholesterol, low-density lipoprotein cholesterol, triglycerides, and blood pressure did not differ significantly between groups at any time point. CONCLUSIONS: A pragmatic ILI consistent with national guidelines and delivered by trained health coaches in primary care produced clinically relevant improvements in cardiometabolic health in an underserved population over 24 months. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02561221.

Sleep extension and metabolic health in male overweight/obese short sleepers: A randomised controlled trial.

While limited evidence suggests that longer sleep durations can improve metabolic health in habitual short sleepers, there is no consensus on how sustained sleep extension can be achieved. A total of 18 men (mean [SD] age 41 [ 9] years), who were overweight/obese (mean [SD] body mass index 30 [3] kg/m2 ) and short sleepers at increased risk of type 2 diabetes were randomised to a 6-week sleep-extension programme based on cognitive behavioural principles (n = 10) or a control (n = 8) group. The primary outcome was 6-week change in actigraphic total sleep time (TST). Fasting plasma insulin, insulin resistance (Homeostatic Model Assessment for Insulin Resistance [HOMA-IR]), blood pressure, appetite-related hormones from a mixed-meal tolerance test, and continuous glucose levels were also measured. Baseline to 6-week change in TST was greater in the sleep-extension group, at 79 (95% confidence interval [CI] 68.90, 88.05) versus 6 (95% CI -4.43, 16.99) min. Change in the sleep-extension and control groups respectively also showed: lower fasting insulin (-11.03 [95% CI -22.70, 0.65] versus 7.07 [95% CI -4.60, 18.74] pmol/L); lower systolic (-11.09 [95% CI -17.49, -4.69] versus 0.76 [95% CI -5.64, 7.15] mmHg) and diastolic blood pressure (-12.16 [95% CI -17.74, -6.59] versus 1.38 [95% CI -4.19, 6.96] mmHg); lower mean amplitude of glucose excursions (0.34 [95% CI -0.57, -0.12] versus 0.05 [95% CI -0.20, 0.30] mmol/L); lower fasting peptide YY levels (-18.25 [95%CI -41.90, 5.41] versus 21.88 [95% CI -1.78, 45.53] pg/ml), and improved HOMA-IR (-0.51 [95% CI -0.98, -0.03] versus 0.28 [95% CI -0.20, 0.76]). Our protocol increased TST and improved markers of metabolic health in male overweight/obese short sleepers.

Association between weight loss, change in physical activity, and change in quality of life following a corporately sponsored, online weight loss program.

BACKGROUND: The physiological benefits associated with corporately sponsored weight loss programs are increasingly well documented. However, less is known about how these programs affect employees' quality of life (QoL). The purpose of the present analysis was to examine the association between weight loss, change in physical activity, and change in QoL following a corporately sponsored, online weight loss program. METHODS: We examined the relationship between weight loss, self-reported change in physical activity, and change in several QoL indices in 26,658 participants (79% women) after the initial 10 weeks of the online weight loss program. The trend in changes in each QoL index with increasing weight loss and change in physical activity was examined using logistic regression analysis. RESULTS: We observed greater improvements in each QoL index with increasing weight loss (p-for-trend, < 0.001) as well as with progressive increases in physical activity (p-for-trend, < 0.001). The combination of increasing weight loss and increases in physical activity were associated with the greatest improvements in each QoL index (additive effect). The percentage of employees reporting improvements in QoL ("improved" or "very much improved") was 64% for energy, 63% for mood, 33% for sleep, 65% for self-confidence, 68% for indigestion, and 39% for musculoskeletal pain. CONCLUSIONS: Among people, who engage with a commercial weight loss program, greater weight loss during the program was associated with greater improvements in QoL, and increases in physical activity further enhanced the QoL-related benefits.

Effect of 2 years of calorie restriction on liver biomarkers: results from the CALERIE phase 2 randomized controlled trial.

PURPOSE: Calorie restriction (CR) is an effective treatment for obesity-related liver and metabolic disease. However, CR studies in individuals without obesity are needed to see if CR could delay disease onset. Liver biomarkers indicate hepatic health and are linked to cardiometabolic disease. Our aim was to examine the effects of a 2-year CR intervention on liver biomarkers in healthy individuals without obesity. METHODS: The Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) study was a 2-year randomized controlled trial. Overall, 218 participants (body mass index: 25.1 ± 1.7 kg/m2) were enrolled into a control group (n = 75) that ate ad libitum (AL), or a CR group (n = 143) that aimed to decrease energy intake by 25%. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and bilirubin were measured during the trial. RESULTS: At month 24, relative to the AL group, ALP (- 7 ± 1 IU/L; P < 0.01) and GGT (- 0.11 ± 0.04 log IU/L; P = 0.02) decreased and bilirubin increased (0.21 ± 0.06 log mg/dL; P < 0.01) in the CR group; no between-group differences in ALT (- 1 ± 1 IU/L; P > 0.99) or AST (2 ± 2 IU/L; P = 0.68) were revealed. However, sex-by-treatment-by-time interactions (P < 0.01) were observed, with CR (vs. control) inducing reduced ALT and GGT and increased AST in men only (P ≤ 0.02). CONCLUSIONS: In metabolically healthy individuals without obesity, 2 years of CR improves several liver biomarkers, with potentially greater improvements in men. These data suggest that sustained CR may improve long-term liver and metabolic disease risk in healthy adults. TRIAL REGISTRATION: Clinicaltrials.gov (NCT00427193). Registered January 2007.

Meal composition during an ad libitum buffet meal and longitudinal predictions of weight and percent body fat change: The role of hyper-palatable, energy dense, and ultra-processed foods.

BACKGROUND: Foods that increase obesity risk are ubiquitous in the US food environment. Such foods may be the target of hedonic eating, which may facilitate weight gain and lead to obesity. The study tested whether meal composition during an ad libitum buffet meal was associated with 1-year weight and percent body fat changes among healthy younger adults without obesity. Hyper-palatable foods (HPF) were the study focus; comparisons were conducted with high energy dense (HED) and ultra-processed foods (UPF). DESIGN: Younger adults without obesity (N = 82; 43% male; mean age 26.8) completed an ad libitum buffet meal and provided body composition measurements at baseline and 1-year follow up. Multiple regression models tested associations between the proportion of the target food consumed (HPF, HED, or UPF) during the ad libitum meal and 1) weight change and 2) percent body fat change. The proportion of HPF was characterized by HPF group, specifically carbohydrate and sodium (CSOD) foods or fat and sodium (FSOD) foods. RESULTS: Participants who consumed a greater proportion of CSOD HPF in their ad libitum buffet meals had significantly greater weight change (b = 0.354, p = .003) and percent body fat change (b = 0.247, p = .036) at 1-year follow up. In contrast, no significant associations were found between the proportion of FSOD HPF, HED, or UPF consumed and anthropometric outcomes (p values = .099-.938). CONCLUSIONS: Eating a greater proportion of hyper-palatable CSOD foods ad libitum appears to be a pattern of hedonic eating, which may increase an individual's risk for weight and body fat gain in early adulthood.

True Interindividual Variability Exists in Postprandial Appetite Responses in Healthy Men But Is Not Moderated by the FTO Genotype.

BACKGROUND: After meal ingestion, a series of coordinated hormone responses occur concomitantly with changes in perceived appetite. It is not known whether interindividual variability in appetite exists in response to a meal. OBJECTIVES: The aim of this study was to 1) assess the reproducibility of appetite responses to a meal; 2) quantify individual differences in responses; and 3) explore any moderating influence of the fat mass and obesity associated (FTO) gene. METHODS: Using a replicated crossover design, 18 healthy men (mean ± SD age: 28.5 ± 9.8 y; BMI: 27.0 ± 5.0 kg/m2) recruited according to FTO genotype (9 AA, 9 TT) completed 2 identical control and 2 identical standardized meal conditions (5025 kJ) in randomized sequences. Perceived appetite and plasma acylated ghrelin, total peptide YY (PYY), insulin, and glucose concentrations were measured before and after interventions as primary outcomes. Interindividual differences were explored using Pearson's product-moment correlations between the first and second replicates of the control-adjusted meal response. Within-participant covariate-adjusted linear mixed models were used to quantify participant-by-condition and genotype-by-condition interactions. RESULTS: The meal suppressed acylated ghrelin and appetite perceptions [standardized effect size (ES): 0.18-4.26] and elevated total PYY, insulin, and glucose (ES: 1.96-21.60). For all variables, SD of change scores was greater in the meal than in the control conditions. Moderate-to-large positive correlations were observed between the 2 replicates of control-adjusted meal responses for all variables (r = 0.44-0.86, P ≤ 0.070). Participant-by-condition interactions were present for all variables (P ≤ 0.056). FTO genotype-by-condition interactions were nonsignificant (P ≥ 0.19) and treatment effect differences between genotype groups were small (ES ≤ 0.27) for all appetite parameters. CONCLUSIONS: Reproducibility of postprandial appetite responses is generally good. True interindividual variability is present beyond any random within-subject variation in healthy men but we detected no moderation by the FTO genotype. These findings highlight the importance of exploring individual differences in appetite for the prevention and treatment of obesity. This trial was registered at clinicaltrials.gov as NCT03771690.

Effect of different doses of supervised aerobic exercise on heart rate recovery in inactive adults who are overweight or obese: results from E-MECHANIC.

PURPOSE: Heart rate recovery (HRR) after exercise is an independent risk factor for cardiovascular disease and mortality. Regular aerobic exercise can improve HRR, yet little is known regarding the dose necessary to promote increases. The aim was to assess the impact of different doses of vigorous-intensity aerobic exercise on HRR in individuals with overweight/obesity. METHODS: Data from 137 sedentary adults with overweight/obesity from E-MECHANIC were analyzed. Participants were randomized to either a moderate-dose exercise group (8 kcal/kg body weight/week; KKW), a high-dose exercise group (20 KKW), or a non-exercise control group. HRR was defined as the difference between peak heart rate (HR) during a graded exercise test and the HR after exactly 1 min of active recovery at 1.5 mph and level grade. RESULTS: Change in HRR did not differ significantly by exercise group; therefore, the data from both exercise groups were combined. The combined exercise group showed an improvement in HRR of 2.7 bpm (95% CI 0.1, 5.4; p = 0.04) compared to the control group. Those participants who lost more weight during the intervention (non-compensators) increased HRR by 6.2 bpm (95% CI 2.8, 9.5; p < 0.01) compared to those who lost less weight (compensators). Multiple linear regression models indicated that improvements in HRR are independently associated with increases in VO2peak (ß = 0.4; 95% CI 0.1, 0.7; p = 0.04) but also influenced by concomitant weight loss (ß = 0.6; 95% CI 0.2, 1.1; p = 0.01). CONCLUSION: Exercise-induced improvements in 1-min HRR are likely due to increases in cardiorespiratory fitness as well as concomitant weight loss.

Change in self-efficacy, eating behaviors and food cravings during two years of calorie restriction in humans without obesity.

Calorie restriction (CR) enhances longevity in humans who are normal weight, overweight and obese. While dietary regimens can change self-efficacy, eating behaviors, and food cravings in individuals with obesity, the responses of these measures to prolonged CR in individuals who are exclusively not obese is unknown. The aim of this analysis was to test the effects of a two-year CR intervention on self-efficacy and eating attitudes and behaviors in humans without obesity by analyzing data from the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy Phase 2 (CALERIE 2) study. Participants (n = 218, BMI range = 21.3-29.0 kg/m2) were randomized to a 25% CR group or an ad libitum (AL) group. Eating attitudes and behaviors and self-efficacy were assessed using validated questionnaires at baseline, month 12, and month 24. Dietary restraint and self-efficacy increased in the CR compared to the AL group (ES ≥ 0.32). Increased self-efficacy was negatively related to weight change (ρ < -0.24). In the CR group, males showed a reduction in cravings for carbohydrates and fats at month 24, whereas females did not. The CR group showed elevations in state hunger, which were transient, and disinhibited eating (ES ≥ 0.37). In individuals without obesity, dietary restraint and self-efficacy could be important in promoting long-term CR for individuals looking to use CR as a tool to improve longevity.

Exploration of associations between the FTO rs9939609 genotype, fasting and postprandial appetite-related hormones and perceived appetite in healthy men and women.

BACKGROUND: The fat mass and obesity-associated gene (FTO) rs9939609 A-allele has been associated with obesity risk. Although the exact mechanisms involved remain unknown, the FTO rs9939609 A-allele has been associated with an impaired postprandial suppression of appetite. OBJECTIVES: To explore the influence of FTO rs9939609 genotype on fasting and postprandial appetite-related hormones and perceived appetite in a heterogeneous sample of men and women. DESIGN: 112 healthy men and women aged 18-50-years-old completed three laboratory visits for the assessment of FTO rs9939609 genotype, body composition, aerobic fitness, resting metabolic rate, visceral adipose tissue, liver fat, fasting leptin, and fasting and postprandial acylated ghrelin, total PYY, insulin, glucose and perceived appetite. Participants wore accelerometers for seven consecutive days for the assessment of physical activity and sedentary behaviour. Multivariable general linear models quantified differences between FTO rs9939609 groups for fasting and postprandial appetite outcomes, with and without the addition of a priori selected physiological and behavioural covariates. Sex-specific univariable Pearson's correlation coefficients were quantified between the appetite-related outcomes and individual characteristics. RESULTS: 95% confidence intervals for mean differences between FTO rs9939609 groups overlapped zero in unadjusted and adjusted general linear models for all fasting (P ≥ 0.28) and postprandial (P ≥ 0.19) appetite-related outcomes. Eta2 values for explained variance attributable to FTO rs9939609 were <5% for all outcomes. An exploratory correlation matrix indicated that associations between fasting and postprandial acylated ghrelin, total PYY and general or abdominal adiposity were also small (r = -0.23 to 0.15, P ≥ 0.09). Fasting leptin, glucose and insulin and postprandial insulin concentrations were associated with adiposity outcomes (r = 0.29 to 0.81, P ≤ 0.033). CONCLUSIONS: Associations between the FTO rs9939609 genotype and fasting or postprandial appetite-related outcomes were weak in healthy men and women.

Effects of sprint interval training on ectopic lipids and tissue-specific insulin sensitivity in men with non-alcoholic fatty liver disease.

PURPOSE: This study examined the feasibility of sprint interval exercise training (SIT) for men with non-alcoholic fatty liver disease (NAFLD) and its effects on intrahepatic triglyceride (IHTG), insulin sensitivity (hepatic and peripheral), visceral (VAT) and subcutaneous adipose tissue (ScAT). METHODS: Nine men with NAFLD (age 41 ± 8 years; BMI 31.7 ± 3.1 kg m-2; IHTG 15.6 ± 8.3%) were assessed at: (1) baseline (2) after a control phase of no intervention (pre-training) and (3) after 6 weeks of SIT (4-6 maximal 30 s cycling intervals, three times per week). IHTG, VAT and ScAT were measured using magnetic resonance spectroscopy or imaging and insulin sensitivity was assessed via dual-step hyperinsulinaemic-euglycaemic clamp with [6,6-D2] glucose tracer. RESULTS: Participants adhered to SIT, completing ≥ 96.7% of prescribed intervals. SIT increased peak oxygen uptake [[Formula: see text] peak: + 13.6% (95% CI 8.8-18.2%)] and elicited a relative reduction in IHTG [- 12.4% (- 31.6 to 6.7%)] and VAT [- 16.9% (- 24.4 to - 9.4%); n = 8], with no change in body weight or ScAT. Peripheral insulin sensitivity increased throughout the study (n = 8; significant main effect of phase) but changes from pre- to post-training were highly variable (range - 18.5 to + 58.7%) and not significant (P = 0.09), despite a moderate effect size (g* = 0.63). Hepatic insulin sensitivity was not influenced by SIT. CONCLUSIONS: SIT is feasible for men with NAFLD in a controlled laboratory setting and is able to reduce IHTG and VAT in the absence of weight loss.

Exercise-induced Changes in Central Adiposity During an RCT: Effect of Exercise Dose and Associations With Compensation.

CONTEXT: Exercise can decrease central adiposity, but the effect of exercise dose and the relationship between central adiposity and exercise-induced compensation is unclear. OBJECTIVE: Test the effect of exercise dose on central adiposity change and the association between central adiposity and exercise-induced weight compensation. METHODS: In this ancillary analysis of a 6-month randomized controlled trial, 170 participants with overweight or obesity (mean ± SD body mass index: 31.5 ± 4.7 kg/m2) were randomized to a control group or exercise groups that reflected exercise recommendations for health (8 kcal/kg/week [KKW]) or weight loss and weight maintenance (20 KKW). Waist circumference was measured, and dual-energy X-ray absorptiometry assessed central adiposity. Predicted weight change was estimated and weight compensation (weight change - predicted weight change) was calculated. RESULTS: Between-group change in waist circumference (control: .0 cm [95% CI, -1.0 to 1.0], 8 KKW: -.7 cm [95% CI, -1.7 to .4], 20 KKW: -1.3 cm [95% CI, -2.4 to -.2]) and visceral adipose tissue (VAT; control: -.02 kg [95% CI, -.07 to .04], 8 KKW: -.01 kg [95% CI, -.07 to .04], 20 KKW: -.04 kg [95% CI, -.10 to .02]) was similar (P ≥ .23). Most exercisers (82.6%) compensated (weight loss less than expected). Exercisers who compensated exhibited a 2.5-cm (95% CI, .8 to 4.2) and .23-kg (95% CI, .14 to .31) increase in waist circumference and VAT, respectively, vs those who did not (P < .01). Desire to eat predicted VAT change during exercise (ß = .21; P = .03). CONCLUSION: In the presence of significant weight compensation, exercise at doses recommended for health and weight loss and weight maintenance leads to negligible changes in central adiposity.

The Personalized Nutrition Study (POINTS): evaluation of a genetically informed weight loss approach, a Randomized Clinical Trial.

Weight loss (WL) differences between isocaloric high-carbohydrate and high-fat diets are generally small; however, individual WL varies within diet groups. Genotype patterns may modify diet effects, with carbohydrate-responsive genotypes losing more weight on high-carbohydrate diets (and vice versa for fat-responsive genotypes). We investigated whether 12-week WL (kg, primary outcome) differs between genotype-concordant and genotype-discordant diets. In this 12-week single-center WL trial, 145 participants with overweight/obesity were identified a priori as fat-responders or carbohydrate-responders based on their combined genotypes at ten genetic variants and randomized to a high-fat (n = 73) or high-carbohydrate diet (n = 72), yielding 4 groups: (1) fat-responders receiving high-fat diet, (2) fat-responders receiving high-carbohydrate diet, (3) carbohydrate-responders receiving high-fat diet, (4) carbohydrate-responders receiving high-carbohydrate diet. Dietitians delivered the WL intervention via 12 weekly diet-specific small group sessions. Outcome assessors were blind to diet assignment and genotype patterns. We included 122 participants (54.4 [SD:13.2] years, BMI 34.9 [SD:5.1] kg/m2, 84% women) in the analyses. Twelve-week WL did not differ between the genotype-concordant (-5.3 kg [SD:1.0]) and genotype-discordant diets (-4.8 kg [SD:1.1]; adjusted difference: -0.6 kg [95% CI: -2.1,0.9], p = 0.50). With the current ability to genotype participants as fat- or carbohydrate-responders, evidence does not support greater WL on genotype-concordant diets. ClinicalTrials identifier: NCT04145466.

Initial weight loss and early intervention adherence predict long-term weight loss during the Promoting Successful Weight Loss in Primary Care in Louisiana lifestyle intervention.

OBJECTIVE: This study tested whether initial weight change (WC), self-weighing, and adherence to the expected WC trajectory predict longer-term WC in an underserved primary-care population with obesity. METHODS: Data from the intervention group (n = 452; 88% women; 74% Black; BMI 37.3 kg/m2 [SD: 4.6]) of the Promoting Successful Weight Loss in Primary Care in Louisiana trial were analyzed. Initial (2-, 4-, and 8-week) percentage WC was calculated from baseline clinic weights and daily at-home weights. Weights were considered adherent if they were on the expected WC trajectory (10% at 6 months with lower [7.5%] and upper [12.5%] bounds). Linear mixed-effects models tested whether initial WC and the number of daily and adherent weights predicted WC at 6, 12, and 24 months. RESULTS: Percentage WC during the initial 2, 4, and 8 weeks predicted percentage WC at 6 (R2 = 0.15, R2 = 0.28, and R2 = 0.50), 12 (R2 = 0.11, R2 = 0.19, and R2 = 0.32), and 24 (R2 = 0.09, R2 = 0.11, and R2 = 0.16) months (all p < 0.01). Initial daily and adherent weights were significantly associated with WC as individual predictors, but they only marginally improved predictions beyond initial weight loss alone in multivariable models. CONCLUSIONS: These results highlight the importance of initial WC for predicting long-term WC and show that self-weighing and adherence to the expected WC trajectory can improve WC prediction.

Mediators of weight change in underserved patients with obesity: exploratory analyses from the Promoting Successful Weight Loss in Primary Care in Louisiana (PROPEL) cluster-randomized trial.

BACKGROUND: Intensive lifestyle interventions (ILIs) stimulate weight loss in underserved patients with obesity, but the mediators of weight change are unknown. OBJECTIVES: We aimed to identify the mediators of weight change during an ILI compared with usual care (UC) in underserved patients with obesity. METHODS: The PROPEL (Promoting Successful Weight Loss in Primary Care in Louisiana) trial randomly assigned 18 clinics (n = 803) to either an ILI or UC for 24 mo. The ILI group received an intensive lifestyle program; the UC group had routine care. Body weight was measured; further, eating behaviors (restraint, disinhibition), dietary intake (percentage fat intake, fruit and vegetable intake), physical activity, and weight- and health-related quality of life constructs were measured through questionnaires. Mediation analyses assessed whether questionnaire variables explained between-group variations in weight change during 2 periods: baseline to month 12 (n = 779) and month 12 to month 24 (n = 767). RESULTS: The ILI induced greater weight loss at month 12 compared with UC (between-group difference: -7.19 kg; 95% CI: -8.43, -6.07 kg). Improvements in disinhibition (-0.33 kg; 95% CI: -0.55, -0.10 kg), percentage fat intake (-0.25 kg; 95% CI: -0.50, -0.01 kg), physical activity (-0.26 kg; 95% CI: -0.41, -0.09 kg), and subjective fatigue (-0.28 kg; 95% CI: -0.46, -0.10 kg) at month 6 during the ILI partially explained this between-group difference. Greater weight loss occurred in the ILI at month 24, yet the ILI group gained 2.24 kg (95% CI: 1.32, 3.26 kg) compared with UC from month 12 to month 24. Change in fruit and vegetable intake (0.13 kg; 95% CI: 0.05, 0.21 kg) partially explained this response, and no variables attenuated the weight regain of the ILI group. CONCLUSIONS: In an underserved sample, weight change induced by an ILI compared with UC was mediated by several psychological and behavioral variables. These findings could help refine weight management regimens in underserved patients with obesity.This trial was registered at clinicaltrials.gov as NCT02561221.

Challenges in defining successful adherence to calorie restriction goals in humans: Results from CALERIE™ 2.

BACKGROUND: The Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE™) phase 2 trial tested the effects of two years of 25% calorie restriction (CR) on aging in humans. CALERIE 2 was one of the first studies to use a graph of predicted weight loss to: 1) provide a proxy of dietary adherence, and 2) promote dietary adherence. Assuming 25% CR, each participant's weight over time was predicted, with upper and lower bounds around predicted weights. Thus, the resulting weight graph included a zone or range of body weights that reflected adherence to 25% CR, and this was named the zone of adherence. Participants were considered adherent if their weight was in this zone. It is unlikely, however, that the entire zone reflects 25% CR. OBJECTIVES: To determine the level of CR associated with the zone of adherence and if the level of CR achieved by participants was within the zone. METHODS: Percent CR associated with the upper and lower bounds of the zone were determined via the Body Weight Planner (https://www.niddk.nih.gov/bwp) for participants in the CALERIE 2 CR group (N = 143). Percent CR achieved by participants was estimated with the intake-balance method. RESULTS: At month 24, the zone of adherence ranged from 10.4(0.0)% to 19.4(0.0)% CR [Mean(SEM)], and participants achieved 11.9(0.7)% CR and were in the zone. CONCLUSION: The results highlight the challenges of: 1) setting a single CR goal vs. a range of acceptable values, and 2) obtaining real-time and valid measures of CR adherence to facilitate adherence.

Calorie restriction improves lipid-related emerging cardiometabolic risk factors in healthy adults without obesity: Distinct influences of BMI and sex from CALERIE™ a multicentre, phase 2, randomised controlled trial.

BACKGROUND: For many cardiovascular risk factors there is no lower limit to which further reduction will result in decreased disease risk; this includes values within ranges considered normal for healthy adults. This seems to be true for new emerging metabolic risk factors identified by innovative technological advances. Further, there seems to be ever evolving evidence of differential responses to lifestyle interventions by sex and body compositions in the normal range. In this secondary analysis, we had the opportunity to test these principles for newly identified molecular biomarkers of cardiometabolic risk in a young (21-50 years), normal weight healthy population undergoing calorie restriction for two years. METHODS: The Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE™) was a 24-month, multicenter, randomized controlled trial (May 2007-November 2012) in healthy, adults without obesity to evaluate the potential for calorie restriction (CR) to promote anti-aging adaptations, including those associated with disease risk. 218 participants (age 37.9 ± 7.2 years and body mass index (BMI) 25.1 ± 1.7 kg/m2, mean±SD) were randomized 2:1 to 24 months of CR (prescribed as 25% reduction from baseline calorie intake) versus ad libitum (AL). Fasting plasma from baseline, 12, and 24 months was used for assessments of lipoproteins, metabolites, and inflammatory markers using nuclear magnetic resonance spectroscopy. FINDINGS: Averaging 11.9% CR, the CR group had reductions at 12 and 24 months in the cardiovascular disease risk markers, apolipoprotein B and GlycA, and risks for insulin resistance and type 2 diabetes-Lipoprotein Insulin Resistance Index and Diabetes Risk Index (all PCRvsAL ≤0.0009). Insulin resistance and diabetes risk improvements resulted from CR-induced alterations in lipoproteins, specifically reductions in triglyceride-rich lipoprotein particles and low-density lipoprotein particles, a shift to larger high-density lipoprotein particles (more effective cholesterol transporters), and reductions in branched chain amino acids (BCAAs) (all PCRvsAL ≤0.004). These CR responses were more pronounced in overweight than normal weight participants and greater in men than women. INTERPRETATION: In normal to slightly overweight adults without overt risk factors or disease, 12 months of ∼12% CR improved newly identified risk markers for atherosclerotic cardiovascular disease, insulin resistance and type 2 diabetes. These markers suggest that CR improves risks by reducing inflammation and BCAAs and shifting lipoproteins from atherogenic to cholesterol transporting. Additionally, these improvements are greater for men and for those with greater BMIs indicating sex and BMI-influences merit attention in future investigations of lifestyle-mediated improvements in disease risk factors. FUNDING: The CALERIE™ trial design and implementation were supported by a National Institutes of Health (NIH) U-grant provided to four institutions, the three intervention sites and a coordinating center (U01 AG022132, U01 AG020478, U01 AG020487 U01 AG020480). For this secondary analysis including sample acquisition and processing, data analysis and interpretation, additional funding was provided by the NIH to authors as follows: R01 AG054840 (MO, VBK); R33 AG070455 (KMH, DCP, MB, SBR, CKM, LMR, SKD, CFP, CJR, WEK); P30 DK072476 (CKM, LMR); and U54 GM104940 (CKM, LMR).

Effect of an office-based intervention on visceral adipose tissue: the WorkACTIVE-P randomized controlled trial.

Office-based activity reduces sedentariness, yet no randomized controlled trials (RCTs) have assessed how such activity influences visceral adipose tissue (VAT). This study examined the effect of an office-based, multicomponent activity intervention on VAT. The WorkACTIVE-P RCT enrolled sedentary office workers (body mass index: 31.4 (standard deviation (SD) 4.4) kg/m2) to an intervention (n = 20) or control (n = 20) group. For 3 months, the intervention group received an office-based pedal desk, further to an intervention promoting its use and increased walking. The control group maintained habitual activity. At baseline and follow-up, VAT, cardiometabolic disease risk markers, physical activity, and food intake were measured. Steps/day were not altered relative to control (P ≥ 0.51), but the pedal desk was utilized for 127 (SD 61) min/day. The intervention reduced VAT relative to control (-0.15 kg; 95% confidence interval (CI) = -0.29 to -0.01; P = 0.04). Moreover, the intervention decreased fasting glucose compared with control (-0.29 mmol/L; 95% CI = -0.51 to -0.06; P = 0.01), but no differences in other cardiometabolic disease markers or food intake were revealed (P ≥ 0.11). A multicomponent intervention decreased VAT in office workers who were overweight or obese. Though longer-term studies are needed, office-based, multicomponent activity regimens may lower cardiometabolic disease risk. Trial registered at ClinicalTrials.gov (NCT02561611). Novelty: In WorkACTIVE-P, a multicomponent activity intervention decreased visceral adipose tissue relative to control in office workers. The intervention also reduced glucose compared with control, though other metabolic risk markers and food intake were not altered. Such multicomponent interventions could help reduce cardiometabolic disease risk, but longer studies are needed.

Preference, Expected Burden, and Willingness to Use Digital and Traditional Methods to Assess Food and Alcohol Intake.

We conducted an online survey to examine the preference, expected burden, and willingness of people to use four different methods of assessing food and alcohol intake such as food/drink record, 24-h recall, Remote Food Photography Method© (RFPM, via SmartIntake® app), and a novel app (PortionSize®) that allows the in-app portion size estimation of foods/drinks by the user. For food (N = 1959) and alcohol (N = 466) intake assessment, 67.3% and 63.3%, respectively, preferred the RFPM/SmartIntake®, 51.9% and 53.4% preferred PortionSize®, 48.0% and 49.3% the food records, and 32.9% and 33.9% the 24-h recalls (difference in preference across all methods was p < 0.001 for food and alcohol intake). Ratings of burden and preference of methods were virtually superimposable, and we found strong correlations between high preference and low expected burden for all methods (all ρ ≥ 0.82; all p < 0.001). Willingness (mean (SD)) to use the RFPM/SmartIntake® (food: 6.6 (2.0); alcohol: 6.4 (2.4)) was greater than PortionSize® (food: 6.0 (2.2); alcohol: 6.0 (2.4); all p < 0.001) and 24-h recalls (food: 6.1 (2.2); alcohol: 5.7 (2.7); p < 0.001), but not different from food records (food: 6.6 (2.0); alcohol: 6.5 (2.3); all p ≥ 0.33). Our results can be used in conjunction with existing data on the reliability and validity of these methods in order to inform the selection of methods for the assessment of food and alcohol intake.

Effect of 8 weeks of supervised overfeeding on eating attitudes and behaviors, eating disorder symptoms, and body image: Results from the PROOF and EAT studies.

The physiological and metabolic effects of experimental overfeeding have been extensively studied, yet only few studies have assessed overfeeding effects on eating behaviors and psychological constructs. We analyzed two 8-week overfeeding studies, the PROOF Study (N = 25; 16 males; 16 African American; 24.1 years; 25.1 kg/m2, inpatient) and the EAT Study (N = 35; 29 males; 20 White; 26.7 years; 25.5 kg/m2, free-living). In both studies, participants were overfed 40% above baseline (daily) energy requirements for eight weeks, consuming all meals under direct supervision. We assessed eating attitudes and behaviors, eating disorder symptoms, and body image via validated questionnaires and visual analog scales at baseline, week (W) 4, and W8, and at two (PROOF: W16-Post, W24-Post) and three (EAT: W12-Post, W20-Post, W32-Post) follow-up visits, respectively. Hunger, desire to eat, and food cravings (carbohydrates, total cravings) decreased during overfeeding in both studies (all Cohen's d effect sizes ≥0.3, all p ≤ .048). Depressive symptoms and fear of fatness increased in both studies (all Cohen's d ≥ 0.4, p ≤ .020), though they were still within normal limits (t-scores ~43-49). Body dissatisfaction increased in both studies during overfeeding (all Cohen's d ≥ 0.4, all p ≤ .044) and remained increased during follow-up (PROOF: W16-Post, Cohen's d = 0.9, p = .004; EAT: W12-Post and W20-Post, all Cohen's d ≥ 0.4, all p ≤ .037). Overfeeding was associated with some deleterious effects, though most returned to baseline during follow-up. However, increases in body dissatisfaction remained up to three months post-overfeeding, highlighting the need to address body image disturbance among people who experience weight gain, even if much of the gained weight is subsequently lost. TRIAL REGISTRATION: The PROOF Study (ClinicalTrials.gov Identifier NCT00565149); the EAT Study (ClinicalTrials.gov Identifier NCT01672632).