UC Riverside

Elucidating genetic and environmental factors that affect physical activity, dietary choices, and their interactions is essential for attempts to ameliorate the obesity epidemic. Using mice selectively bred for high voluntary wheel-running behavior (four replicate HR lines) and their four non-selected control (C) lines, I investigated early-life effects on adult physical activity, preference for Western diet (WD), and whole-animal metabolic rate and fuel usage with WD.

Early-life access to wheels increased adult wheel running but had no statistical effect on spontaneous physical activity (SPA) of adult males in their attached home cages. The early-exercise effect on wheel running disappeared after one week, but body mass was reduced throughout the experiment. Early-life exercise reduced circulating leptin concentrations in HR lines, but increase them in C lines (genotype-by-environment interaction).

Both HR and C mice highly preferred WD, high in fat and sucrose, over standard chow. After 17 days of wheel acclimation, but not after six days, HR had a stronger preference for WD than did C mice, which further increased their wheel running and decreased their SPA. When a separate set of mice was switched from standard chow to WD, the effects on wheel running depended on both sex and linetype in a complicated fashion.

Fuel usage was studied indirectly by whole-animal respirometry. Female HR and C mice did not differ statistically in minimal resting metabolic rate, but the former had higher levels of maximal oxygen consumption during voluntary wheel running. Contrary to my hypothesis, I found no evidence for a reduced respiratory exchange ratio (which would indicate greater reliance on lipids) in HR mice at rest, during maximal voluntary exercise or measured over a 23-hour period, either on standard chow or with WD.

Overall, my research provides evidence for important, genetically based differences between the HR and C lines, sex differences, and sex-by-linetype interactions. These results encourage use of the HR mice as an anti-obesity model in further studies of the complex physiological and neurobiological mechanisms that interact with sex and genetic background in ways that may allow some individuals to resist the adverse effects of obesogenic environments.