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Obesity is a chronic disease that affects more than 650 million adults worldwide. Obesity not only is a significant health concern on its own, but predisposes to cardiometabolic comorbidities, including coronary heart disease, dyslipidemia, hypertension, type 2 diabetes, and some cancers. Lifestyle interventions effectively promote weight loss of 5% to 10%, and pharmacological and surgical interventions even more, with some novel approved drugs inducing up to an average of 25% weight loss. Yet, maintaining weight loss over the long-term remains extremely challenging, and subsequent weight gain is typical. The mechanisms underlying weight regain remain to be fully elucidated. The purpose of this Pennington Biomedical Scientific Symposium was to review and highlight the complex interplay between the physiological, behavioral, and environmental systems controlling energy intake and expenditure. Each of these contributions were further discussed in the context of weight-loss maintenance, and systems-level viewpoints were highlighted to interpret gaps in current approaches. The invited speakers built upon the science of obesity and weight loss to collectively propose future research directions that will aid in revealing the complicated mechanisms involved in the weight-reduced state., (© 2023 The Obesity Society.)

Objective: This study tested the hypothesis that greater weight variability (WV; measured as root mean square error [RMSE]) during the first year of life predicts weight gain at year two and greater WV during the second year of life predicts greater weight gain at year three., Methods: This was a prospective study using mother and offspring data from the Avon Longitudinal Study of Parents and Children. Infant z-BMI (BMI z score) and WV scores were calculated separately during years one and two. Maternal demographic, weight, and nursing-related measures were also used in analyses., Results: Sample sizes in year-one and year-two analyses were 814 (448 male; 366 female) and 783 (432 male; 351 female), respectively. RMSE in year one significantly predicted z-BMI change in year two (β [SE]: 0.32 [0.12]; p = 0.01; adjusted R 2 = 0.07), controlling for z-BMI change in year one and z-BMI at birth. Similar significant prediction was found using year-two RMSE for year-three z-BMI (β [SE]: 0.33 [0.14]; p = 0.02; adjusted R 2 = 0.10). Maternal characteristics were not related to RMSE in year one or year two., Conclusions: Previous findings that WV predicts subsequent increases in body mass in adults were, for the first time, extended to infants., (© 2021 The Obesity Society.)

Objective: Response early in weight loss treatment predicts long-term weight change. Weight variability, independent of absolute early weight change, may also relate to long-term outcomes. This study examined whether weight variability early in treatment predicted later weight loss and maintenance., Methods: Participants were 183 completers of a yearlong behavioral weight loss program (mean age = 51, 81% female, 69% white, mean BMI = 35  kg/m 2 ). Weight variability was calculated using weights from the first 6 and 12 weekly treatment sessions. Multiple linear regressions examined whether weight variability predicted subsequent weight change 6, 12, and 24 months later., Results: Weight variability over 6- and 12-week periods predicted less subsequent weight loss at 12 months (6-week: β = 0.18, P = 0.02; 12-week: β = 0.33, P < 0.01) and 24 months (6-week: β = 0.17, P = 0.03; 12-week: β = 0.15, P = 0.05). Relationships held when adjusting for covariates. Weight variability was more strongly associated with 6-month weight change in men than women (β = 0.27, P = 0.01)., Conclusions: Elevated weight variability early in a weight loss program predicted poor long-term outcomes, possibly reflecting inconsistent weight control behaviors. Tracking weight variability could prove useful for improving treatment outcomes., (© 2017 The Obesity Society.)

Objective: This study was designed to compare weight loss through a traditional behavioral treatment (BT) approach that integrated skills for managing the obesogenic food environment (BT + E) with an approach that integrated environmental and acceptance-based skills (BT + EA). Moderators were examined as an exploratory aim., Methods: Adults (N = 283) were randomly assigned to treatment condition and provided with 26 group-based sessions over the course of 12 months. Weight was measured in the clinic at months 0, 6, and 12., Results: Change in weight over time did not significantly differ by condition. However, race significantly moderated the effect of condition on weight loss (P = 0.04), such that African-American participants lost less weight than non-Hispanic white participants in the BT (6.2% vs. 11.5%) and BT + E conditions (6.6% vs. 12.2%), but weight loss in these two groups was similar in the BT + EA condition (9.4% vs. 11.5%). Among African Americans, rates of achieving a clinically significant weight loss (i.e., > 5%) at 12 months were higher in BT + EA (80%) than BT (57%) or BT + E (48%) (P = 0.04)., Conclusions: This innovative behavioral approach shows promise for treatment of African Americans, which is notable given the lack of progress to date addressing racial disparities in obesity intervention efficacy., (© 2017 The Obesity Society.)

Objective: Prior neuroimaging research has shown that restrained and unrestrained eaters demonstrate differential brain activation in response to food cues that parallels their food intake in lab studies. These findings were extended by comparing brain activation in response to food cues in normal weight nondieters, historical dieters, and current dieters under the conditions that mimicked past lab studies., Methods: Participants (N = 30) were shown pictures of highly and moderately palatable food and neutral cues while being scanned in an fMRI BOLD paradigm following an 8-h fast and again after a liquid meal., Results: In the Fed state, historical dieters showed elevated reward circuitry activation in response to highly palatable food, as compared to nondieters and current dieters. In contrast, current dieters did not show the same pattern of activation as historical dieters, despite their shared history of frequent weight-loss dieting., Conclusions: The parallels between eating behavior and regional brain activation across groups suggest that (1) a neurophysiological response which could represent a vulnerability to overeat exists in some normal weight young women that may increase susceptibility to weight gain in the long term, and (2) current dieting temporarily reverses this vulnerability., (Copyright © 2013 The Obesity Society.)

Objective: To compare the presence or absence of meal replacements (MRs) and an energy density (ED) intervention to facilitate weight loss maintenance., Design and Methods: A total of 238 overweight primary care patients (mean body mass index = 39.5 kg/m(2) ) began the study; 132 completed the 12-week weight loss phase. Participants were randomly assigned to one of four maintenance conditions formed by crossing the presence or absence of MRs (MR+/MR-) and of the ED program (ED+/ED-) during a subsequent 9-month maintenance phase. Follow-up assessments occurred 1 and 2 years after treatment termination., Results: Participants initially lost 6.1 kg. Analyses of variance based on weight change from the beginning of the maintenance phase to the 2-year follow-up produced a significant interaction. All groups except ED+/MR- regained substantial weight during follow-up; the ED+/MR- group regained significantly less weight than the control group at both follow-up assessments. No significant effects of treatment were found for several variables that were expected to mediate these outcomes., Conclusions: Because weight losses achieved in lifestyle change programs for obesity are rarely maintained, the superior outcome achieved by the ED+/MR- condition is notable. Nonetheless, methodological issues and inability to identify a potential mediator of this outcome make replication of this finding essential., (© 2013 The Obesity Society.)

Objective: To determine whether acceptance-based behavioral treatment (ABT) would result in greater weight loss than standard behavioral treatment (SBT), and whether treatment effects were moderated by interventionist expertise or participants' susceptibility to eating cues. Recent research suggests that poor long-term weight-control outcomes are due to lapses in adherence to weight-control behaviors and that adherence might be improved by enhancing SBT with acceptance-based behavioral strategies., Design and Methods: Overweight participants (n = 128) were randomly assigned to 40 weeks of SBT or ABT., Results: Both groups produced significant weight loss, and when administered by experts, weight loss was significantly higher in ABT than SBT at post-treatment (13.17% vs. 7.54%) and 6-month follow-up (10.98% vs. 4.83%). Moreover, 64% of those receiving ABT from experts (vs. 46% for SBT) maintained at least a 10% weight loss by follow-up. Moderation analyses revealed a powerful advantage, at follow-up, of ABT over SBT in those potentially more susceptible to eating cues. For participants with greater baseline depression symptomology, weight loss at follow-up was 11.18% in ABT versus 4.63% in SBT; other comparisons were 10.51% versus 6.00% (emotional eating), 8.29% versus 6.35% (disinhibition), and 9.70% versus 4.46% (responsivity to food cues). Mediation analyses produced partial support for theorized food-related psychological acceptance as a mechanism of action., Conclusions: Results offer strong support for the incorporation of acceptance-based skills into behavioral weight loss treatments, particularly among those with greater levels of depression, responsivity to the food environment, disinhibition, and emotional eating, and especially when interventions are provided by weight-control experts., (Copyright © 2013 The Obesity Society.)

Obesity has been promoted by a food environment that encourages excessive caloric intake. An understanding of how the food environment contributes to obesogenic eating behavior in different types of individuals may facilitate healthy weight control efforts. In this study, Ecological Momentary Assessment (EMA) via palmtop computers was used to collect real-time information about participants' environment and eating patterns to predict overeating (i.e., greater than usual intake during routine meals/snacks, and eating outside of a participant's normal routine) that could lead to weight gain. Thirty-nine women (BMI = 21.6 ± 1.8; age = 20.1 ± 2.0 years; 61% white) of normal weight (BMI 18.5-25) completed the Three Factor Eating Questionnaire and the Power of Food Scale (PFS), and carried a palmtop computer for 7-10 days, which prompted them to answer questions about eating events, including a count of the types of good tasting high-calorie foods that were available. None of the self-report measures predicted overeating, but BMI interacted with the number of palatable foods available to predict overeating (P = 0.035). Compared to leaner individuals who reported a relatively low frequency of overeating regardless of the availability of palatable food, the probability of overeating among heavier individuals was very low in the absence of palatable food, but quickly increased in proportion to the number of palatable foods available. Our findings suggest that the eating behavior of those with higher relative weights is susceptible to the presence of palatable foods in the environment. Individuals practicing weight control may benefit from limiting their exposure to good tasting high-calorie food in their immediate environment.

The construct of disinhibition, as measured by the Eating Inventory, was recently found to have two factors: internal disinhibition (eating in response to cognitive and emotional cues) and external disinhibition (eating in response to environmental cues). This study examined whether early changes in disinhibition that occurred during a weight loss program predicted later weight loss maintenance. Participants were adults enrolled in a weight loss treatment study (n = 81, 16% men, BMI = 38.4 +/- 6.5 kg/m(2)). Two-thirds of participants were African Americans. Participants received a uniform, meal-replacement-based weight loss program in months 1-3 and one of four nutritionally focused programs for weight loss maintenance in months 4-12. Disinhibition and weight were assessed at clinic visits. Change in internal disinhibition from months 1-3 (i.e., the weight loss period) significantly predicted change in weight from month 4 to 12 (i.e., the weight maintenance period); this remained significant when treatment group, age, gender, ethnicity, baseline weight, baseline depression, baseline internal disinhibition, and initial weight loss were controlled for (P = 0.03). A comparable analysis examining change in external disinhibition found that it was not a significant predictor of weight maintenance (P = 0.43). Participants who experienced the biggest decreases in internal disinhibition during the initial phase of treatment had the most success maintaining their weight loss in the next phase of treatment. Long-term weight loss outcomes may be improved by spending sufficient treatment time teaching strategies for reducing eating in response to internal cues.

Background: Failure to maintain weight losses in lifestyle change programs continues to be a major problem and warrants investigation of innovative approaches to weight control., Objective: The goal of this study was to compare two novel group interventions, both aimed at improving weight loss maintenance, with a control group., Methods and Procedures: A total of 103 women lost weight on a meal replacement-supplemented diet and were then randomized to one of three conditions for the 14-week maintenance phase: cognitive-behavioral treatment (CBT); CBT with an enhanced food monitoring accuracy (EFMA) program; or these two interventions plus a reduced energy density eating (REDE) program. Assessments were conducted periodically through an 18-month postintervention. Outcome measures included weight and self-reported dietary intake. Data were analyzed using completers only as well as baseline-carried-forward imputation., Results: Participants lost an average of 7.6 +/- 2.6 kg during the weight loss phase and 1.8 +/- 2.3 kg during the maintenance phase. Results do not suggest that the EFMA intervention was successful in improving food monitoring accuracy. The REDE group decreased the energy density (ED) of their diets more so than the other two groups. However, neither the REDE nor the EFMA condition showed any advantage in weight loss maintenance. All groups regained weight between 6- and 18-month follow-ups., Discussion: Although no incremental weight maintenance benefit was observed in the EFMA or EFMA + REDE groups, the improvement in the ED of the REDE group's diet, if shown to be sustainable in future studies, could have weight maintenance benefits.

Myotonic dystrophy type 1 (DM1) is associated with both skeletal and cardiac muscle involvement. The aim of the present study was to determine whether familial clustering is observed in the severity of muscle involvement in DM1. We evaluated 51 sibling groups constituting 112 patients with genetically-verified DM1. The siblings were similar to each other in age, cytosine-thymine-guanine (CTG) repeat length, age at disease onset, muscular impairment rating score, and electrocardiographic markers of cardiac conduction disease. After adjusting for the similarities between siblings in age and CTG repeat length, the siblings remained similar to each other in measures of both skeletal and cardiac muscle involvement. These results suggest that factors other than CTG repeat length play a role in the severity and progression of the degenerative skeletal and cardiac muscle disease in DM1.