Increased physical activity may mediate weight gain through increases in energy expenditure (EE) and reductions in energy balance (EB). Methods for modulating mouse EE (e.g. – exercise, chemical uncouplers, etc.) have confounding effects, however, it is known that mouse EE linearly increases at temperatures below the thermoneutral zone.


Herein we performed indirect calorimetry experiments in male and female mice at two housing temperatures (20C vs. 30C) to assess how divergent EE impacts 7-day low-fat (LFD) and high-fat, high-sucrose (HFHS) diet-induced weight gain and body composition changes.


Mice housed at 30C have ~40% lower total EE compared to 20C mice regardless of diet or sex (p<0.0001). Energy intake (EI) was also reduced in 30C mice (~35% and ~25% for LFD & HFHS, respectively) compared to 20C mice regardless of sex (p<0.01). EB was increased with HFHS the same for both 20C & 30C mice (p<0.01). Importantly, no differences were observed in cage activity. For weight gain, no differences were observed during LFD; however, HFHS increased weight gain regardless of temperature or sex (p<0.01). Interestingly, no weight gain differences were observed between females due to HFHS at either temperature; while 30C male mice gained ~50% more weight on HFHS compared to 20C males (p<0.05), and ~80% more weight compared to 30C females (p<0.05). Further, HFHS produced increased gain in fat mass (FM) across all groups. 30C mice had ~50% greater increases in FM compared to 20C mice (p<0.05), and female had ~35% less FM gain compared to males on HFHS regardless of temperature (p<0.05). Gain in fat-free mass was greater in 20C females on HFHS compared to both 20C LFD females (85%, p<0.01), and 20C HFHS males (2.6-fold, p<0.01). Importantly, the 30C females fed HFHS had ~60% less gain in fat-free mass compared to 20C females (p<0.01).


Together, these data reveal an interaction between divergent EE and sex to impact diet-induced short-term weight gain and body composition.