Different Fasting Methods Combined With Running Exercise Regulate Glucose Metabolism via AMPK/SIRT1/BDNF Pathway in Mice

AIM: Intermittent fasting or exercise could be used as an adjunct to regulating abnormal glucose metabolism. However, the mechanism of action of intermittent fasting and exercise to regulate normal glucose metabolism is still unclear. We want to investigate the regulatory effect and mechanism of action of intermittent fasting combined with exercise on glucose metabolism in normal mice. METHODS: All mice were randomized into six groups of 12 animals each. The effects of 6-week alternate-day fasting (ADF) or time-restricted fasting (TRF) combined with running exercise on blood glucose regulation in normal C57BL/6 male mice were evaluated. The expressions of the proteins involved, AMPK, SIRT1, BDNF, MAPK, and Nrf2 signaling pathways, were detected by western blot. RESULTS: Running exercise could increase muscle glycogen content in mice, and both types of fasting combined with running exercise could decrease glycated serum protein and hepatic glycogen content. Furthermore, we found that fasting and exercise up-regulated the expressions of AMPK, PGC-1α, Glut-4, SIRT1, and PPAR-γ protein, and down-regulated the expression of FoxO1 protein, modulating the ability of the liver and skeletal muscle to uptake glucose and convert glucose-lipid metabolism. Meanwhile, fasting and running exercise increase hippocampal BDNF, activating the MAPK and Nrf2/HO-1 pathways to enhance antioxidant capacity. The regulatory effect of TRF on the above proteins was significantly greater than ADF. CONCLUSION: TRF was more effective than ADF in regulating glucose metabolism. Taken together, the regulatory effect of fasting combined with exercise on glucose metabolism was better than the effect of mono-fasting.