Review Article

The role of REV-ERB in NASH

Kristine Griffett1, Matthew E. Hayes2, Michael P. Boeckman1, Thomas P. Burris2
1 Center for Clinical Pharmacology, Washington University in St. Louis and University of Health Sciences & Pharmacy, St. Louis, MO 63110, USA
2 University of Florida Genetics Institute, Gainesville, FL 32610, USA
Correspondence to: Thomas P. Burris:,
DOI: 10.1038/s41401-022-00883-w
Received: 19 October 2021
Accepted: 28 January 2022
Advance online: 25 February 2022


REV-ERBs are atypical nuclear receptors as they function as ligand-regulated transcriptional repressors. The natural ligand for the REV-ERBs (REV-ERBα and REV-ERBβ) is heme, and heme-binding results in recruitment of transcriptional corepressor proteins such as N-CoR that mediates repression of REV-ERB target genes. These two receptors regulate a large range of physiological processes including several important in the pathophysiology of non-alcoholic steatohepatitis (NASH). These include carbohydrate and lipid metabolism as well as inflammatory pathways. A number of synthetic REV-ERB agonists have been developed as chemical tools and they show efficacy in animal models of NASH. Here, we will review the functions of REV-ERB with regard to their relevance to NASH as well as the potential to target REV-ERB for treatment of this disease.
Keywords: NASH; REV-ERB; Heme; circadian clock; lipid and glucose metabolism; inflammation

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