Wheel running eliminates high-fat preference and enhances leptin signaling in the ventral tegmental area.

Voluntary wheel running (WR) is a form of physical activity in rodents that influences ingestive behavior. This study examined the effects of WR on dietary preference and the potential role of leptin in mediating these effects. In a two-diet choice paradigm in which both palatable high-fat (HF) food and standard laboratory chow were provided ad libitum, rats displayed a strong preference for the former and chose to eat almost exclusively the HF diet over chow in sedentary conditions. With free access to running wheels, however, rats exhibited no preference for the HF food and consumed equal gram amounts of both chow and HF diets. The total daily caloric consumption during WR in the dietary choice protocol was equivalent to the amount of calories consumed daily by WR rats with only chow or only HF diet available, yet significantly less than sedentary chow caloric consumption. Two days after initiating WR, leptin signal transduction was examined in multiple selected brain sites following leptin injection into the third cerebral ventricle. The maximal leptin-stimulated STAT3 phosphorylation was enhanced only in the ventral tegmental area (VTA), but not in the arcuate nucleus, lateral hypothalamus, dorsal medial or ventral medial hypothalamus, or substantia nigra. In conclusion, wheel running appears to act either as an independent reinforcing factor or as a more favored activity to substitute for the consumption of a palatable HF diet, thus eliminating the preference for the HF food. Moreover, WR enhances leptin signaling specifically in the VTA, suggestive of a WR-evoked mechanism of heightened leptin function in the VTA to curb the drive to consume palatable HF foods.