Exercise plays a critical role in regulating glucose homeostasis and body weight. However, the mechanism of exercise on metabolic functions associated with the CNS has not been fully understood. C57BL6 male mice (n=45) were divided into three groups: normal chow diet, high-fat diet (HFD) treatment, and HFD along with voluntary running wheel exercise training for 12 weeks. Metabolic function was examined by the Comprehensive Lab Animal Monitoring System and magnetic resonance imaging; phenotypic analysis included measurements of body weight, food intake, glucose and insulin tolerance tests, as well as insulin and leptin sensitivity studies. By immunohistochemistry, the amount changes in the phosphorylation of signal transducer and activator of transcription 3, neuronal proliferative maker Ki67, apoptosis positive cells as well as pro-opiomelanocortin (POMC)-expressing neurons in the arcuate area of the hypothalamus was identified. We found that 12 weeks of voluntary exercise training partially reduced body weight gain and adiposity induced by an HFD. Insulin and leptin sensitivity were enhanced in the exercise training group verses the HFD group. Furthermore, the HFD-impaired POMC-expressing neuron is remarkably restored in the exercise training group. The restoration of POMC neuron number may be due to neuroprotective effects of exercise on POMC neurons, as evidenced by altered proliferation and apoptosis. In conclusion, our data suggest that voluntary exercise training improves metabolic symptoms induced by HFD, in part through protected POMC-expressing neuron from HFD and enhanced leptin signaling in the hypothalamus that regulates whole-body energy homeostasis.
Keywords: exercise; hypothalamus; metabolism; mouse; obesity.
© 2016 Society for Endocrinology.