Gender-dimorphic regulation of muscular proteins in response to high fat diet and sex steroid hormones

To investigate the roles of gender-dependent obesity, we investigated the effects of high fat diet (HFD) and sex steroid hormones on the fiber-type dependent expression of contractile and metabolic regulatory pathway proteins in gastrocnemius (G) and soleus (S) muscle tissue of male and female rats. The results revealed that estrogen (E2) negatively influences body weight gain, whereas testosterone (DHT) has positive effects. Additionally, E2 appeared to play an essential role in initiating muscle contraction and mediating glucose and lipid metabolism events via AMPK and AKT pathways. The elevated expression of ERα contributed to the expression of muscular proteins in a fiber-type and gender-dependent manner. E2 treatment increased the protein levels of AMPK, thereby activating downstream lipid metabolic proteins such as PPARγ, ACSL1, LPL, and A-FABP. Such cooperatively activating proteins enhanced fatty acid oxidation, attenuating TG accumulation. E2 stimulated AKT and AMPK activation suggests that these proteins enhanced GLUT4 expression. More importantly, the S muscle of HFD-fed control females showed higher expressions of MYH, TPM1α, and TnI, while only MYH and TnI were upregulated in males treated with E2, indicating that females may be more resistant to HFD-increased metabolic complications. Similarly, E2 treatment enhanced metabolic regulatory proteins in males, indicating that they are more susceptible to metabolic dysregulation than females. To the best our knowledge, this is the first report to distinguish the fatty acid uptake and oxidation between two types of muscle in both genders.