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. 2022 May;43(5):1133-1140.
doi: 10.1038/s41401-022-00883-w. Epub 2022 Feb 25.

The role of REV-ERB in NASH

Kristine Griffett  1 , Matthew E Hayes  2 , Michael P Boeckman  1 , Thomas P Burris  3
Affiliations

The role of REV-ERB in NASH

Kristine Griffett et al. Acta Pharmacol Sin. 2022 May.

Abstract

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: Heme; NASH; REV-ERB; circadian clock; inflammation; lipid and glucose metabolism.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
General organization of nuclear receptor structure and the REV-ERBs. The REV-ERB receptors lack the activation function-2 (AF-2) region within the C-terminal domain. Sequence identity (amino acid sequence was obtained from Uniprot) of each of the REV-ERB domains was compared and represented by percent identity as shown in the REV-ERBβ structure. The N-terminal domain was too variable for comparison between the isoforms. The A/B region, C region (DNA binding domain), D region (hinge), and E regions (ligand-binding domain) are indicated.
Fig. 2
Fig. 2
Synthetic REV-ERB ligands. Several unique chemical scaffolds that regulate REV-ERB activity are illustrated.
See this image and copyright information in PMC

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