Genetic variation of lean body mass, changes of appetite, and weight loss in response to diet interventions: the POUNDS Lost trial.

AIMS Emerging evidence has implicated lean body mass (LBM) in regulating appetite and adiposity. We investigated whether the genetic risk score (GRS) for LBM modified the effects of weight-loss diets on changes in appetite and adiposity among overweight and obese individuals. MATERIALS AND METHODS In the 2-year Preventing Overweight Using Novel Dietary Strategies (POUNDS Lost) trial, we included 692 adults who were randomly assigned to 1 of 4 diets varying in macronutrient intake. A GRS was calculated using 5 single nucleotide polymorphisms (SNPs) associated with LBM. RESULTS The LBM-GRS was not associated with the baseline LBM measured by dual-energy x-ray absorptiometry in a subgroup (50%) of the study population. We found that LBM-GRS had significantly different associations with changes in appetite from baseline to 6 months according to the low-/high-fat group (p-interaction<0.001, 0.021, 0.005, and 0.024 for total appetite score, hunger, fullness, and prospective consumption, respectively). Individuals with lower LBM-GRS (indicating a greater genetic predisposition to LBM) was associated with greater decreases in the total appetite score (p < 0.001), hunger (p = 0.01), fullness (p = 0.001), and prospective consumption (p = 0.019) in the low-fat diet group, whereas no significant associations with these appetite measures were observed in the high-fat diet group. In addition, lower LBM-GRS was associated with a greater reduction in body weight (p = 0.003) and waist circumference (p = 0.011) among participants in a low-fat diet group, while no associations were observed in the high-fat diet group. The interactions attenuated along with weight regain from 6 months to 2 years. CONCLUSIONS Our findings suggest that genetic variation of LBM may differentially associate with appetite changes, and subsequently related to changes in body weight and waist circumference, according to dietary fat intake. This article is protected by copyright. All rights reserved.