Emerging functions of the nuclear receptor LRH-1 in liver physiology and pathology

Biochim Biophys Acta Mol Basis Dis. 2021 Aug 1;1867(8):166145. doi: 10.1016/j.bbadis.2021.166145. Epub 2021 Apr 20.

Abstract

Nuclear receptors play pleiotropic roles in cell differentiation, development, proliferation, and metabolic processes to govern liver physiology and pathology. The nuclear receptor, liver receptor homolog-1 (LRH-1, NR5A2), originally identified in the liver as a regulator of bile acid and cholesterol homeostasis, was recently recognized to coordinate a multitude of other hepatic metabolic processes, including glucose and lipid processing, methyl group sensing, and cellular stress responses. In this review, we summarize the physiological and pathophysiological functions of LRH-1 in the liver, as well as the molecular mechanisms underlying these processes. This review also focuses on the recent advances highlighting LRH-1 as an attractive target for liver-associated diseases, such as non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC).

Keywords: HCC; Hepatocytes; NAFLD; NASH; NR5A2.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / metabolism
  • Cell Differentiation / physiology
  • Homeostasis / physiology
  • Humans
  • Liver / metabolism*
  • Liver Neoplasms / metabolism
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Receptors, Cytoplasmic and Nuclear / metabolism*

Substances

  • Receptors, Cytoplasmic and Nuclear