Female mice respond differently to costly foraging versus food restriction

Experimental manipulation of foraging costs per food reward can be used to study the plasticity of physiological systems involved in energy metabolism. This approach is useful for understanding adaptations to natural variation in food availability. Earlier studies have shown that animals foraging on a fixed reward schedule decrease energy intake and expenditure. However, the extent to which these changes depend on decreased food intake or increased foraging costs per se has never been tested. We manipulated foraging costs per food reward in female Hsd:ICR(CD-1) laboratory mice, comparing animals faced with low (L) and high (H) foraging costs to non-foraging animals receiving a food restriction (R) matched to the intake of H animals. Mice in the H group ran as much as L mice did but ate significantly less. They concurrently reduced daily energy expenditure and resting metabolic rate, decreased the size of major metabolic organs and utilized body fat stores; mass-specific resting metabolic rate did not differ between groups. We found evidence that these alterations in energy balance may carry fitness costs. As a secondary response to our experimental treatment, H females and, eventually, some R females ceased to show signs of estrous cyclicity. Surprisingly, results of an immune challenge with keyhole limpet hemocyanin showed that primary immune response did not differ between L and H groups, and was actually higher in R mice. Our results demonstrate that high foraging costs per se--the combination of high activity and low food intake--have pronounced physiological effects in female mice.