Voluntary exercise in the C57B1/6J mouse: phenotypic effects of varying dietary fat levels and hippocampal gene expression differences between high-level and low-level exercisers

The drive to exercise voluntarily likely results from complex interactions between genes in many organ systems and various psychological parameters, such as motivation and the perception of fatigue. Reproducible variations in exercise intensity and duration are well established in laboratory rodents, but the genes responsible remain largely unknown. Also, to date, studies addressing the adaptive changes to exercise that might prevent dietary-induced obesity have focused primarily on energy intake and nutrient oxidation/partitioning, as opposed to genetics. We hypothesize that increased voluntary physical activity may be a normal mechanism in certain rodent strains to deter dietary-induced obesity and that in an inbred strain of mice, environmentally sensitive genes must be responsible for observed differences in individual voluntary exercise performance. To study this theory, we have designed a set of experiments that establish an animal model to address whether different gene expression profiles can be detected using microarrays and confirmed with quantitative real-time PCR (qRT-PCR) in distinct exercise phenotypes. We also used the model to address whether dietary manipulations affect voluntary exercise performance in a single strain of inbred mice susceptible to dietary-induced obesity. We determined that animals weaned onto high fat diet exercise at levels significantly higher than those weaned onto low fat diet. These animals were able to maintain body weight and decrease body fat after three weeks of exercise. We also report the results and validation of three microarray comparisons using pooled RNA from the hippocampi of exercising animals. These data suggest that several genes from the HSP 70 family, specifically several molecular chaperones localized to the endoplasmic reticulum, are differentially regulated in running versus sedentary animals at several exercise time points. We suggest that increased voluntary physical activity may be an adaptive response in male C57Bl/6J mice that prevents dietary-induced obesity on high fat diets, and we demonstrate that differential gene expression profiles related to exercise could be identified in the brain using microarrays and qRT-PCR. We conclude that genes from the molecular chaperone family, a well-described environmentally sensitive gene family, are differentially regulated in response to voluntary exercise in an inbred mouse strain