# Sex Hormones and Their Receptors Regulate Liver Energy Homeostasis

## TL;DR

This paper reviews how sex hormones and their receptors influence liver metabolism and energy balance, potentially offering new targets for treating fatty liver disease.

## Contribution

The paper integrates recent findings on how estrogen and androgen receptors specifically regulate lipid and glucose metabolism in the liver.

## Key findings

- Estradiol in females reduces lipogenesis and gluconeogenesis while promoting cholesterol secretion and glucose catabolism.
- Testosterone in males increases insulin receptor expression and glycogen synthesis while decreasing glucose uptake and lipogenesis.
- Sex hormone receptors are suggested as potential targets for preventing hepatic steatosis.

## Abstract

The liver is one of the most essential organs involved in the regulation of energy homeostasis. Hepatic steatosis, a major manifestation of metabolic syndrome, is associated with imbalance between lipid formation and breakdown, glucose production and catabolism, and cholesterol synthesis and secretion. Epidemiological studies show sex difference in the prevalence in fatty liver disease and suggest that sex hormones may play vital roles in regulating hepatic steatosis. In this review, we summarize current literature and discuss the role of estrogens and androgens and the mechanisms through which estrogen receptors and androgen receptors regulate lipid and glucose metabolism in the liver. In females, estradiol regulates liver metabolism via estrogen receptors by decreasing lipogenesis, gluconeogenesis, and fatty acid uptake, while enhancing lipolysis, cholesterol secretion, and glucose catabolism. In males, testosterone works via androgen receptors to increase insulin receptor expression and glycogen synthesis, decrease glucose uptake and lipogenesis, and promote cholesterol storage in the liver. These recent integrated concepts suggest that sex hormone receptors could be potential promising targets for the prevention of hepatic steatosis.