Removal of a high-fat diet, but not voluntary exercise, reverses obesity and diabetic-like symptoms in male C57BL/6J mice

OBJECTIVE Both the consumption of high-fat diets and exercise are known to produce alterations in metabolism and behavior. This study focuses on the effects of a change to a low-fat diet from a high-fat diet and voluntary exercise on obesity, type-2 diabetic-like symptoms, and locomotor behavior in male C57BL/6J mice. DESIGN Mice were initially given either a high-fat diet or regular chow, along with a cage with a running-wheel to mimic exercise, or one without, to determine to what extend exercise affects these symptoms. Then half of the mice given a high-fat diet were switched to regular chow to ascertain if the switch in diet would improve type-2 diabetic-like and obesity symptoms. RESULTS Wheel-running alone produced an improvement in insulin in mice continuously fed a high-fat diet ( p =0.006), but running-wheels did not produce any further improvements in mice with regular chow replacement ( p =0.999) or in controls ( p =0.996). Replacement of a high-fat diet with regular chow led to physiological improvements in insulin ( p =0.012) and leptin ( p <0.001), glucose tolerance ( p <0.001), and obesity ( p <0.001), more so than exercise alone. Mice consuming a high-fat diet without a wheel exhibited reduced home-cage activity compared to controls after the diet switch ( p =0.030), while no reduction was found in running-wheel activity between high-fat diet and regular chow consuming mice after switching diets ( p =0.516). CONCLUSIONS These results suggest that exercise is only partially beneficial to improving health outcomes in mice consuming a high-fat diet, whereas incorporating a better diet, even without exercise, improves quality of health and can suppress T2DM symptoms and related conditions more so than exercise alone.