Appetite-Related Responses to Overfeeding and Longitudinal Weight Change in Obesity-Prone and Obesity-Resistant Adults.

OBJECTIVE: Appetite responses to 3 days of overfeeding (OF) were examined as correlates of longitudinal weight change in adults classified as obesity prone (OP) or obesity resistant (OR). METHODS: OP (n = 22) and OR (n = 30) adults consumed a controlled eucaloric and OF diet (140% of energy needs) for 3 days, followed by 3 days of ad libitum feeding. Hunger and satiety were evaluated by visual analog scales. Ghrelin and peptide YY (PYY) levels were measured during a 24-hour inpatient visit on day 3. Body weight and composition were measured annually for 4.0 ± 1.3 years. RESULTS: Dietary restraint and disinhibition were greater in OP than OR (mean difference: 3.5 ± 1.2 and 3.3 ± 0.9, respectively; P < 0.01) participants, and disinhibition was associated with longitudinal weight change (n = 48; r = 0.35; P = 0.02). Compared with the eucaloric diet, energy intake fell significantly in OR participants following OF (P = 0.03) but not in OP (P = 0.33) participants. Twenty-four-hour PYY area under the curve values increased with OF in OR (P = 0.02) but not in OP (P = 0.17) participants. Furthermore, changes in PYY levels with OF correlated with measured energy intake (r = -0.36; P = 0.01). CONCLUSIONS: Baseline disinhibition and PYY responses to OF differed between OP and OR adults. Dietary disinhibition was associated with 5-year longitudinal weight gain. Differences in appetite regulation may underlie differences in propensity for weight gain.

A Toolbox Approach to Obesity Treatment in Urban Safety-Net Primary Care Clinics: a Pragmatic Clinical Trial.

BACKGROUND: There is a need for new strategies to improve the success of obesity treatment within the primary care setting. OBJECTIVE: To determine if patients offered low out-of-pocket cost weight management tools achieved more weight loss compared to usual care. DESIGN: Twelve-month pragmatic clinical weight loss trial with a registry-based comparator group performed in primary care clinics of an urban safety-net hospital. PARTICIPANTS: From a large clinical registry, we randomly selected 428 patients to have the opportunity to receive the intervention. INTERVENTIONS: Medical weight management tools-partial meal replacements, recreation center vouchers, pharmacotherapy, commercial weight loss program vouchers, and a group behavioral weight loss program-for $5 or $10 monthly. Patients chose their tools, could switch tools, and could add a second tool at 6 months. MAIN MEASURES: The primary outcome was the proportion of intervention-eligible patients who achieved ≥ 5% weight loss. The main secondary outcome was the proportion of on-treatment patients who achieved ≥ 5% weight loss. KEY RESULTS: Overall, 71.3% (305 of 428) had available weight measurement data/PCP visit data to observe the primary outcome. At 12 months, 23.3% (71 of 305) of intervention-eligible participants and 15.7% (415 of 2640) of registry-based comparators had achieved 5% weight loss (p < 0.001). Of the on-treatment participants, 34.5% (39 of 113) achieved 5% weight loss. Mean percentage weight loss was - 3.15% ± 6.41% for on-treatment participants and - 0.30% ± 6.10% for comparators (p < 0.001). The initially preferred tools were meal replacements, pharmacotherapy, and recreation center passes. CONCLUSIONS: Access to a variety of low out-of-pocket cost weight management tools within primary care resulted in ≥ 5% body weight loss in approximately one quarter of low-income patients with obesity. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT01922934.

Associations Among Dietary Fat Oxidation Responses to Overfeeding and Weight Gain in Obesity-Prone and Resistant Adults.

OBJECTIVE: This study tested the hypothesis that 3 days of overfeeding (OF) decreases dietary fat oxidation and predicts longitudinal weight change in adults classified as obesity prone (OP) and obesity resistant (OR) based on self-identification and personal and family weight history. Changes in diurnal profiles of plasma metabolites and hormones were measured to probe mechanisms. METHODS: Adults identified as OP (n = 22; BMI: 23.9  ±  2.4 kg/m2 ) and OR (n = 30; BMI: 20.5  ±  2.2 kg/m2 ) completed 3 days of eucaloric (EU) feeding and 3 days of OF. On day 3, the 24-hour total and dietary fat oxidation was measured using room calorimetry and an oral 14 C tracer. Plasma glucose, insulin, triglycerides, and nonesterified fatty acid (NEFA) concentrations were frequently sampled over 24 hours. Body composition was measured annually for 4.0  ±  1.4 years in a subsample (n = 19 OP and 23 OR). RESULTS: Dietary fat oxidation over 24 hours was not altered by OF versus EU (P = 0.54). Weight gain in OP correlated with lower nocturnal NEFA concentrations during OF (r  = -0.60; P = 0.006) and impaired fuel selection over 24 hours (metabolic inflexibility, wake respiratory quotient-sleep respiratory quotient) (r = -0.48; P  = 0.04). CONCLUSIONS: Short-term OF did not alter dietary fat oxidation. Lower nocturnal NEFA availability and metabolic inflexibility to overfeeding may be factors contributing to weight gain.

Effects of Education and Experience on Primary Care Providers' Perspectives of Obesity Treatments during a Pragmatic Trial.

OBJECTIVE: To examine the impact of a 1-year pragmatic obesity trial on primary care providers' (PCPs) perspectives of treatment. METHODS: PCPs from four intervention clinics (PCP-I) and five control clinics (PCP-C) completed pre- and postintervention surveys on weight-loss counseling, comfort discussing obesity treatments, and perceived effectiveness of interventions; questions were rated on 0 to 10 Likert scales. Only PCP-I received patient updates and education about obesity management. RESULTS: Eighty PCPs completed preintervention surveys (pre: 71% female, 71% physicians); 82 PCPs completed postintervention surveys (post: 66% female, 70% physicians). PCPs were most comfortable discussing exercise before and after the trial (pre PCP-C: 8.22 [1.44], mean [standard deviation (SD)]; post PCP-C: 8.37 [1.24]; P = 0.8; pre/post PCP-I: 7.88 [1.51] vs. 7.80 [1.71]; P = 0.3). PCPs were initially least comfortable discussing phentermine/topiramate extended release (ER) but developed significantly more comfort after the trial, to a greater degree among PCP-I (pre/post PCP-C: 2.86 [2.66] vs. 3.73 [2.72], P < 0.001; pre/post PCP-I: 4.00 [2.57] vs. 6.17 [2.27], P < 0.001). After the trial, both PCPs rated exercise significantly less effective for weight loss, with a greater decrease in effectiveness rations among PCP-I (pre/post PCP-C: 7.73 [1.94] vs. 6.93 [2.35], P = 0.017; pre/post PCP-I: 6.27 [2.69] vs. 5.15 [2.31], P = 0.001). Both PCPs rated phentermine (pre/post PCP-C: 5.03 [2.05] vs. 5.50 [2.12], P = 0.002; pre/post PCP-I: 5.70 [1.64] vs. 6.83 [1.18], P = 0.001) and phentermine/topiramate ER (pre/post PCP-C: 3.91 [2.33] vs. 5.47 [2.54], P < 0.001; pre/post PCP-I: 5.58 [2.21] vs. 7.02 [1.47], P < 0.001) significantly more effective after the trial, though ratings were higher among PCP-I. CONCLUSIONS: PCPs initially overvalued exercise and undervalued weight-loss medications. PCPs exposed to education and experience gave higher comfort and effectiveness ratings to weight-loss medications.

Free-Living Responses in Energy Balance to Short-Term Overfeeding in Adults Differing in Propensity for Obesity.

OBJECTIVE: Free-living adaptive responses to short-term overfeeding (OF) were explored as predictors of longitudinal weight change in adults classified as having obesity resistance (OR) or obesity proneness (OP) based on self-identification and personal/family weight history. METHODS: Adults identified as OP (n = 21; BMI: 23.8 ± 2.5 kg/m2 ) and OR (n = 20; BMI: 20.2 ± 2.1 kg/m2 ) completed 3 days of eucaloric feeding (EU; 100% of energy needs) and 3 days of OF (140% of energy needs). Following each condition, adaptive responses in physical activity (PA), total daily energy expenditure, ad libitum energy intake, and energy balance were objectively measured for 3 days in a free-living environment. Body mass and composition were measured annually by using dual-energy x-ray absorptiometry for 5 years. Adaptive responses to OF were correlated with 5-year changes in body mass and composition. RESULTS: Increases in sedentary time correlated with longitudinally measured changes in fat mass (r = 0.34, P = 0.04) in the cohort taken as a whole. Those with OP reduced their levels of PA following OF, whereas those with OR maintained or increased their PA. No other variables were found to correlate with weight gain. CONCLUSIONS: Failure to decrease sedentary behavior following short-term OF is one mechanism that may be contributing to fat mass gain.

Ability to adjust nocturnal fat oxidation in response to overfeeding predicts 5-year weight gain in adults.

OBJECTIVE: To determine whether metabolic responses to short-term overfeeding predict longitudinal changes in body weight. METHODS: Twenty-four-hour energy expenditure (EE) and substrate utilization were measured at baseline in a room calorimeter following 3 days of eucaloric and hypercaloric feeding (40% excess) in a sample of lean adults (n: 34; age: 28 ± 2 y; BMI: 22 ± 3 kg/m2 ). Body mass and fat mass (dual-energy x-ray absorptiometry) were measured annually for 5 years. Regression analyses examined whether changes in EE and fuel use with overfeeding predicted body weight and composition changes over 5 years. RESULTS: Overfeeding increased EE and reduced fat oxidation when examined over the 24-hour, waking, and nocturnal periods. Absolute change in body mass over 5 years was 3.0 ± 0.6 kg (average rate of change = 0.7 ± 0.1 kg/y, P < 0.001). Lower nocturnal (but not 24-hour or waking) fat oxidation (r = -0.42, P = 0.01) and EE (r = -0.33, P = 0.05) with overfeeding were the strongest predictors of 5-year weight gain. When adjusted for covariates, changes in nocturnal fat oxidation and EE with overfeeding predicted 41% of the variance in weight change (P = 0.02). CONCLUSIONS: Failure to maintain fat oxidation at night following a period of overfeeding appears to be associated with a metabolic phenotype favoring weight gain.

Effect of frequent interruptions of prolonged sitting on self-perceived levels of energy, mood, food cravings and cognitive function.

BACKGROUND: While physical activity has been shown to improve cognitive performance and well-being, office workers are essentially sedentary. We compared the effects of physical activity performed as (i) one bout in the morning or (ii) as microbouts spread out across the day to (iii) a day spent sitting, on mood and energy levels and cognitive function. METHODS: In a randomized crossover trial, 30 sedentary adults completed each of three conditions: 6 h of uninterrupted sitting (SIT), SIT plus 30 min of moderate-intensity treadmill walking in the morning (ONE), and SIT plus six hourly 5-min microbouts of moderate-intensity treadmill walking (MICRO). Self-perceived energy, mood, and appetite were assessed with visual analog scales. Vigor and fatigue were assessed with the Profile of Mood State questionnaire. Cognitive function was measured using a flanker task and the Comprehensive Trail Making Test. Intervention effects were tested using linear mixed models. RESULTS: Both ONE and MICRO increased self-perceived energy and vigor compared to SIT (p < 0.05 for all). MICRO, but not ONE, improved mood, decreased levels of fatigue and reduced food cravings at the end of the day compared to SIT (p < 0.05 for all). Cognitive function was not significantly affected by condition. CONCLUSIONS: In addition to the beneficial impact of physical activity on levels of energy and vigor, spreading out physical activity throughout the day improved mood, decreased feelings of fatigue and affected appetite. Introducing short bouts of activity during the workday of sedentary office workers is a promising approach to improve overall well-being at work without negatively impacting cognitive performance. TRIAL REGISTRATION: NCT02717377 , registered 22 March 2016.

Twenty-four hour total and dietary fat oxidation in lean, obese and reduced-obese adults with and without a bout of exercise.

BACKGROUND: It has been hypothesized that obese and reduced-obese individuals have decreased oxidative capacity, which contributes to weight gain and regain. Recent data have challenged this concept. OBJECTIVE: To determine (1) whether total and dietary fat oxidation are decreased in obese and reduced-obese adults compared to lean but increase in response to an acute exercise bout and (2) whether regular physical activity attenuates these metabolic alterations. DESIGN: We measured 24-hr total (whole-room calorimetry) and dietary fat (14C-oleate) oxidation in Sedentary Lean (BMI = 21.5±1.6; n = 10), Sedentary Obese (BMI = 33.6±2.5; n = 9), Sedentary Reduced-Obese (RED-SED; BMI = 26.9±3.7; n = 7) and in Physically Active Reduced-Obese (RED-EX; BMI = 27.3±2.8; n = 12) men and women with or without an acute exercise bout where energy expended during exercise was not replaced. RESULTS: Although Red-SED and Red-EX had a similar level of fatness, aerobic capacity and metabolic profiles were better in Red-EX only compared to Obese subjects. No significant between-group differences were seen in 24-hr respiratory quotient (RQ, Lean: 0.831±0.044, Obese: 0.852±0.023, Red-SED: 0.864±0.037, Red-EX: 0.842±0.039), total and dietary fat oxidation. A single bout of exercise increased total (+27.8%, p<0.0001) and dietary (+6.6%, p = 0.048) fat oxidation across groups. Although exercise did not impact RQ during the day, it decreased RQ during sleep (p = 0.01) in all groups. Red-EX oxidized more fat overnight than Red-SED subjects under both resting (p = 0.036) and negative energy balance (p = 0.003) conditions, even after adjustment for fat-free mass. CONCLUSION: Obese and reduced-obese individuals oxidize as much fat as lean both under eucaloric and negative energy balance conditions, which does not support the hypothesis of reduced oxidative capacity in these groups. Reduced-obese individuals who exercise regularly have markers of metabolic health similar to those seen in lean adults. Both the acute and chronic effects of exercise were primarily observed at night suggesting an important role of sleep in the regulation of lipid metabolism.

The effects of overfeeding on spontaneous physical activity in obesity prone and obesity resistant humans.

Despite living in an environment that promotes weight gain in many individuals, some individuals maintain a thin phenotype while self-reporting expending little or no effort to control their weight. When compared with obesity prone (OP) individuals, we wondered if obesity resistant (OR) individuals would have higher levels of spontaneous physical activity (SPA) or respond to short-term overfeeding by increasing their level of SPA in a manner that could potentially limit future weight gain. SPA was measured in 55 subjects (23 OP and 32 OR) using a novel physical activity monitoring system (PAMS) that measured body position and movement while subjects were awake for 6 days, either in a controlled eucaloric condition or during 3 days of overfeeding (1.4 × basal energy) and for the subsequent 3 days (ad libitum recovery period). Pedometers were also used before and during use of the PAMS to provide an independent measure of SPA. SPA was quantified by the PAMS as fraction of recording time spent lying, sitting, or in an upright posture. Accelerometry, measured while subjects were in an upright posture, was used to categorize time spent in different levels of movement (standing, walking slowly, quickly, etc.). There were no differences in SPA between groups when examined across all study periods (P > 0.05). However, 3 days following overfeeding, OP subjects significantly decreased the amount of time they spent walking (-2.0% of time, P = 0.03), whereas OR subjects maintained their walking (+0.2%, P > 0.05). The principle findings of this study are that increased levels of SPA either during eucaloric feeding or following short term overfeeding likely do not significantly contribute to obesity resistance although a decrease in SPA following overfeeding may contribute to future weight gain in individuals prone to obesity.

Brown fat activity is not apparent in subjects with HIV lipodystrophy and increased resting energy expenditure.

The HIV lipodystrophy (LD) syndrome is associated with increased resting energy expenditure (REE), but the basis of this hypermetabolism has not been determined. The objective of this pilot study was to determine if brown fat is activated in subjects with HIV LD and increased REE. In this descriptive study of four subjects with HIV LD and marked hypermetabolism, REE was measured by indirect calorimetry and brown fat activity was determined by (18)F-fluorodeoxyglucose (FDG) positron-emission tomography (PET) combined with anatomic computed tomography (CT). Brown fat activity was not apparent in any subject with HIV LD and resting hypermetabolism. Therefore, brown fat activation is unlikely to be the principal cause of the increased REE associated with the HIV LD syndrome. Evidence of adaptive thermogenesis has been demonstrated in this syndrome, but this study suggests that tissues other than brown adipose tissue (BAT) are responsible. Further understanding of the chronic hypermetabolism associated with HIV LD could provide new insights into the regulation of energy balance.

Continuous glucose profiles in obese and normal-weight pregnant women on a controlled diet: metabolic determinants of fetal growth.

OBJECTIVE: We sought to define 24-h glycemia in normal-weight and obese pregnant women using continuous glucose monitoring (CGM) while they consumed a habitual and controlled diet both early and late in pregnancy. RESEARCH DESIGN AND METHODS: Glycemia was prospectively measured in early (15.7 ± 2.0 weeks' gestation) and late (27.7 ± 1.7 weeks' gestation) pregnancy in normal-weight (n = 22) and obese (n = 16) pregnant women on an ad libitum and controlled diet. Fasting glucose, triglycerides (early pregnancy only), nonesterified fatty acids (FFAs), and insulin also were measured. RESULTS: The 24-h glucose area under the curve was higher in obese women than in normal-weight women both early and late in pregnancy despite controlled diets. Nearly all fasting and postprandial glycemic parameters were higher in the obese women later in pregnancy, as were fasting insulin, triglycerides, and FFAs. Infants born to obese mothers had greater adiposity. Maternal BMI (r = 0.54, P = 0.01), late average daytime glucose (r = 0.48, P < 0.05), and late fasting insulin (r = 0.49, P < 0.05) correlated with infant percentage body fat. However, early fasting triglycerides (r = 0.67, P < 0.001) and late fasting FFAs (r = 0.54, P < 0.01) were even stronger correlates. CONCLUSIONS: This is the first study to demonstrate that obese women without diabetes have higher daytime and nocturnal glucose profiles than normal-weight women despite a controlled diet both early and late in gestation. Body fat in infants, not birth weight, was related to maternal BMI, glucose, insulin, and FFAs, but triglycerides were the strongest predictor. These metabolic findings may explain higher rates of infant macrosomia in obese women, which might be targeted in trials to prevent excess fetal growth.

Differences in eating behaviors between nonobese, weight stable young and older adults.

Habitual dietary intake, dietary cognitive restraint (CR), disinhibition and hunger are eating behaviors that influence energy balance in both young and older adults. Since the prevalence of overweight and obesity in older adults is steadily rising, it is important to identify eating behavior adaptations that allow individuals to maintain a healthy body weight with advancing age. The association of age with habitual dietary intake, dietary CR, dishinhibition and hunger was examined in 30 older (60-72 years) and 30 younger (18-25 years) nonobese, weight stable, nondieting healthy adults pair-matched by age group for sex, physical activity level (active >150 min of physical activity per week, sedentary <150 min of physical activity per week) and BMI. Dietary CR was significantly greater and hunger was significantly less in older compared to young adults (both P<0.05). Disinhibition scores, habitual energy and macronutrient intake did not differ between age groups. These results indicate that weight management in older, nonobese adults may be facilitated by increased dietary CR and decreased susceptibility to hunger with age. Additionally, changes in energy and macronutrient intake may not be necessary for successful weight management with advancing age.