Sex difference in metabolic diseases and the role of estrogen in this sex-dependent regulation
(A) In premenopausal conditions, females show lower risk of metabolic diseases and higher estrogen levels than males, mainly due to the activated PI3K-Akt pathway. The females exhibit metabolic health, insulin sensitivity, and glucose tolerance. However, the difference is normalized by menopausal transition, hallmarked by decreased estrogen secretion in females. (B) Ovariectomized (OVX) females exhibit metabolic diseases (such as diabetes, cardiovascular disease, and fatty liver disease), insulin resistance, and glucose intolerance. Administration of estrogen in males and OVX females improves metabolic health, insulin sensitivity and glucose tolerance, normalizing the sex difference. The potential target of estrogen is the activation of PI3K/Akt signaling.