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

Diabetes Obes Metab. 2020 Dec;22(12):2305-2315. doi: 10.1111/dom.14155. Epub 2020 Aug 20.


Aim: To investigate whether the genetic risk score (GRS) for lean body mass (LBM) modified the effects of weight-loss diets on changes in appetite and adiposity among overweight and obese individuals.

Participants and methods: In the 2-year Preventing Overweight Using Novel Dietary Strategies (POUNDS Lost) trial, we included 692 adults who were randomly assigned to one of four diets varying in macronutrient intake. A GRS was calculated using five single nucleotide polymorphisms 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 the LBM-GRS had significantly different associations with changes in appetite from baseline to 6 months according to low- or high-fat diet group (P-interaction < 0.001, 0.021, 0.005 and 0.024 for total appetite score, hunger, fullness and prospective consumption, respectively). 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 participants 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 greater reduction in body weight (P = 0.003) and waist circumference (P = 0.011) among participants in the 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 in LBM may be differentially associated with appetite changes, and may subsequently be related to changes in body weight and waist circumference, according to dietary fat intake.

Keywords: appetite; epidemiology; genetic risk score; lean body mass; weight loss.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Appetite* / genetics
  • Body Mass Index
  • Diet, Reducing
  • Humans
  • Overweight
  • Polymorphism, Single Nucleotide
  • Prospective Studies
  • Weight Loss* / genetics