Abstract
In this study we examined whether spontaneous locomotor activity could restore the leptin resistance induced by high fat diet (HFD) feeding in rats. Adult male rats were given HFD (fat content 60%) to make obese animal model. There was no difference in calorie intake between normal diet fed and HFD fed rats. On 50 days of HFD feeding, body weight, fat pad weight and the serum leptin level were increased. In these obese rats icv injection of leptin showed no inhibitory effect on food intake. These rats were moved to running wheel cage, in which they can run voluntarily. On 10 days of voluntary running in the wheel cage, fat pad weight and blood leptin level tended to decrease, and icv leptin injection inhibited food intake. The intracellular signal of leptin receptor activation was estimated by phosphorylation of STAT3 (pSTAT3) protein using immunohistochemistry in the brain of icv leptin injected rats. In HFD fed rats, the number of pSTAT3 positive cell was decreased in the arcuate nucleus (ARC) and the ventromedial nucleus of the hypothalamus (VMH). Voluntary running for 10 days increased the number of pSTAT3 positive cell in the VMH, but not in the ARC. These results suggest that 10-day voluntary running in the wheel cage restores the leptin resistance and the pSTAT3 signals within the VMH might be involved in this restoration of leptin resistance. [J Physiol Sci. 2008;58 Suppl:S94]