Mice with low metabolic rates are not susceptible to weight gain when fed a high-fat diet.

OBJECTIVE: Mice divergently selected for high or low food intake (FI) at constant body mass differ in their resting metabolic rates (RMRs). Low-intake individuals (ML) have significantly lower RMR (by 30%) compared with those from the high-intake line (MH). We hypothesized that MLs might, therefore, be more likely to increase their body and fat mass when exposed to a high-fat diet (HFD). RESEARCH METHODS AND PROCEDURES: We exposed both lines to a diet with 44.9% calories from fat for 3 weeks while measuring FI, fecal production, and body mass and then returned the mice to standard chow. RESULTS: When exposed to the HFD, both lines significantly decreased their FI (MH, 40% to 45%; ML, 31% to 35%). This decrease occurred simultaneously with a significant increase in apparent energy absorption efficiency (AEAE). When returned to chow, FI and AEAE returned to the levels observed prior to HFD exposure. Because of the adjustments in FI, the absorbed energy was maintained in the MLs and, thus, body mass remained constant. The MH individuals overcompensated for the elevated energy content and AEAE on the HFD and, therefore, absorbed lower energy than when feeding on chow. These mice also did not significantly change their body mass when on the HFD and must have made adjustments in their energy expenditures. Both lines and both sexes increased in fat content on the HFD, but these effects were not different between lines or sexes. DISCUSSION: We found no support for the hypothesis that mice with low RMRs were more susceptible to weight gain when fed the HFD.