The Physiology Of the WEight Reduced State (POWERS) study: overview and study design

Obesity is a multifactorial disease caused by physiological and environmental factors. Adults who have obesity are at increased risk for several additional chronic and infectious diseases, resulting in reduced life expectancy, compared to those with lower body mass indices. Weight loss (WL) has several clinical benefits to reducing these risks. However, among those who intentionally lose weight, it is common for some, or all, of the lost weight to be regained. There is evidence that changes affecting energy intake or expenditure, including metabolic adaptations in the weight-reduced state, work against maintaining WL. The Physiology Of the WEight Reduced State consortium (POWERS) designed a study to describe behavioral and metabolic adaptations to the weight reduced state and to examine their contributions to weight variability following WL. This is accomplished by quantifying physiological, psychosocial, behavioral and other factors before and after a behavioral intervention that induces WL. The primary goal of POWERS is to identify factors that explain the variability in weight change following intentional weight loss. This multi-center project includes a POWERS-designed WL intervention implemented at two clinical centers for 205 enrolled participants. Those losing at least 7% of their pre-intervention weight and attaining weight stability are followed in a 1-year observational phase that includes sequential physiological and behavioral phenotyping. It is anticipated that 70% of those enrolled in the WL program will enter the observational phase of the study and that 100 will complete the study. The primary outcome is weight change during the observational period with primary independent variables measuring energy intake and energy expenditure. Detailed endophenotypes of energy intake and energy expenditure are assessed using a combination of biospecimens, neuroimaging, objective measures (e.g., doubly labeled water, calorimetry, accelerometry, polysomnography), self-report questionnaires, and interviews to address their contributions to weight change variability up to 1 year following WL.