The Mediation of Hepatic Lipogenesis Through Estrogens

Estrogens have been shown to protect against various diseases and disastrous metabolic consequences of poor diets. Although a large body of research demonstrates estrogen's ability to control food intake, adipogenesis, and oxidative stress, research regarding the effects of estrogens on hepatic lipogenesis, steatosis, and non-alcoholic fatty liver disease is only now accumulating. Estrogen deficiency in both human and rodent models directly results in the upregulation of hepatic lipogenic signaling - in both serum and hepatic triglyceride content - which leads to the development of fatty liver. In all models, estrogen replacement completely reverses these outcomes. Similar to the endogenous estrogen hormone, plant-derived phytoestrogens also appear to have beneficial effects related to prevention of hepatic lipogenic signaling and steatosis in rodent models. Additionally, such compounds can completely overcome the hepatic consequences that result from estrogen deficiency. While published research strongly supports that estrogens, both endogenous and exogenous, can protect against hepatic lipogenic signaling that can contribute to the development of non-alcoholic fatty liver diseases and adverse weight gain, little research exists on elucidating the mechanism behind this protection. Various pathways have been suggested, including manipulation of both leptin and signal transducer and activator of transcription 3 (STAT3) signaling. However, the discovery of x-box protein 1 elicits the identification of another potential pathway through which estrogen may be working. While the supportive work is strong, further research is needed to determine the mechanism behind the protection by estrogens from hepatic lipogenesis and associated diseases.