Liver is one of the most important organs involved in the 25 of energy homeostasis. Hepatic steatosis, an important hallmark of metabolic syndrome causes imbalance between lipid formation and breakdown, glucose production and catabolism, and cholesterol synthesis and secretion. Various epidemiological studies have suggested that there is gender disparity in the prevalence in fatty liver disease and sex hormones are crucially implicated in regulating hepatic steatosis. 

Liver steatosis, the hallmark feature of nonalcoholic fatty liver disease (NAFLD), is due to the excess of triglyceride (TG) accumulation within the hepatocytes. Its incidence is commonly associated with low levels of high density lipoprotein cholesterol (HDL-C) and high levels of low density lipoprotein cholesterol (LDL-C) in the circulation. Evidences demonstrate higher plasma level of LDL-C and lower plasma level of HDL-C in men and postmenopausal women in contrast to premenopausal women, indicative of the fact that lower circulating estrogen levels may enhance fat deposition in the liver.

Estradiol (E2) reduce lipoprotein lipase activity along with promotion of lipolysis by increasing expression of hormone-sensitive lipase and adipose triglycerides lipase in the liver, which in turn inhibits lipogenic gene expression and lipid uptake in the liver. Thus, as evident by numerous studies, estrogen signaling is crucial in both males and females in the regulation of lipogenesis.

Moreover, liver enzymes may also be controlled by circulating estrogen levels. A study showed that the subtle oscillations of estrogens taking place during the estrous cycle are adequate to impact liver gene expression, and that estrogen receptors are implicated in the pulsatile synthesis of fatty acids and cholesterol in the liver. Therefore, this study emphasised the significance of the maintenance of estrogen oscillation to limit fat deposition in the hepatic tissues in females, estrogen signaling via ER-α might cause this metabolically protective effect of estrogen.

Source: Shen M, Shi H. Sex Hormones and Their Receptors Regulate Liver Energy Homeostasis. Int J Endocrinol. 2015;2015:294278.