Gender dimorphism of body mass perception and regulation in mice

According to the set-point theory of body mass, changes in body mass are perceived by the body, leading to activation of compensatory feedback mechanisms, which in turn restores the set-point body mass. However, this theory is still under debate. To test if mass per se might be sensed and regulated, we implanted loads corresponding to 10% (HI) or 2% (LO, control) of body mass into mice in addition to sham-operated mice (SO). We recorded body mass, food intake, energy expenditure and body composition over 14 weeks. Both male and female mice showed an initial stress-induced loss of body mass, which was more pronounced in males. Subsequently, male HI mice displayed a permanently decreased biological body mass (MBB, body mass exclusive of the implant mass), equivalent to approximately half of the mass of the implant, and obtained by a decrease in fat mass compared to SO males. In contrast, female HI mice rapidly recovered and maintained their initial MBB and body composition following a mass load. Initial lean body mass was maintained in all male and female groups, and energy intake was similar in all male and female groups. Body mass changes could not be explained by measurable changes in energy intake or expenditure. We conclude that changes in body mass are perceived and partially compensated in male but not in female mice, suggesting that mass-specific regulation of body mass might not play a major role in overall body mass regulation. Different compartments of the body are possibly regulated by different signals and stimuli. Our results suggest that lean body mass rather than body mass per se seems to be tightly regulated. Higher efficiency of energy utilization in females compared to males could explain the gender-specific changes in energy balance.