Exercise improves glucose and lipid metabolism in high fat diet feeding male mice through androgen/androgen receptor-mediated metabolism regulatory factors.

Exercise alleviates high fat diet (HFD)-induced glycolipid metabolism disorders, but the mechanisms are not discovered totally. Low androgen/androgen receptor (AR) levels are associated with glycolipid metabolism disorders in males, and androgen/AR modulate glycolipid metabolism-related regulators such as peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1-α), Forkhead box O1 (FoxO1), phosphoenolpyruvate carboxy kinase (PEPCK) and stearyl-coenzyme A desaturase 1 (SCD1). In the present study, we blockaded androgen (by castration) and inhibited or activated AR activity (by AR antagonist flutamide and agonist S4, respectively) to clarify androgen/AR's roles in exercise-induced alleviation of glycolipid metabolism disorders in male high fat diet (HFD) feeding mice and the underlying mechanisms. We found that: (1) exercise reversed HFD-induced glycolipid metabolism disorders, including restoring fasting blood glucose (FBG), glucose tolerance, TC and TG, accompanied with the increases of serum testosterone and AR in muscle and liver. (2) castration exacerbated HFD-induced impairment of glucose tolerance and increases of TC and TG, and abolished the lowering effect of exercise on FBG and TC. Flutamide further impaired glucose tolerance, increased plasm LDL content, and attenuated exercise-induced improvements of FBG and TG content. (3) exercise reduced the levels of FoxO1 and SCD1, increased PGC-1α in muscle and liver of HFD mice; whereas castration and flutamide reversed exercise-induced improvements of these indicators. Furthermore, S4 rectified the levels of FoxO1, PGC-1α and SCD1 in HFD mice even in absence of androgen. In conclusion, androgen/AR, especially AR, play important roles in alleviating glycolipid metabolism disorders in HFD mice at sedentary and exercise states, which might fulfill through FOXO1, PGC-1α and SCD1.