Genetically determined lean mass and dietary response

Weight loss attenuates many obesity-related co-morbidities, but is difficult to sustain with dietary change. Dietary adherence, not macronutrient composition, is a better predictor of weight loss. Weight loss-induced endocrine changes promote food intake and increase energy efficiency, contributing to the difficulty with dietary adherence and weight regain. Macronutrient preference is partly genetically determined, suggesting that personalized dietary interventions might be more successful. In this issue, Li et al. report that a genetic risk score comprising the cumulative weighted effects of variants previously associated with increased lean mass is associated with increased satiety and weight loss 6 months after initiating a low- but not a high-fat diet. The effects were attenuated by 2 years. These findings suggest that genetic variants may influence response to specific diet. Further studies are necessary to assess whether genetically determined lean mass is causally associated with dietary response. Significant progress has recently been made in identifying additional genetic determinants of lean mass, which will enable such investigations and potentially inform future nutritional studies.