Fig. 1: Overview of known and emerging nuclear receptors as targets in metabolic dysfunction-associated liver diseases (MASLD).

A Representation of nuclear receptors (NRs) bound to DNA response elements in a liver cell. NRs, such as, e.g., peroxisome proliferator-activated receptors (PPARs), liver X receptors (LXRs), and others, can form dimers (homo- or heterodimers with retinoid X receptor [RXR]) to regulate gene expression. NRs are depicted as squares A and B, red and blue circles represent respective ligands, cyan and yellow spheres represent recruited coregulators (CR). B General domain structures of nuclear receptors, including domains A/B (containing the transactivation domain), C (DNA-binding domain), D (hinge region), E (ligand-binding domain), and sometimes F (variable C-terminal domain, not depicted here). C Hallmarks of MASLD, formerly known as non-alcoholic fatty liver disease (NAFLD), along with a list of nuclear receptors involved in fatty liver disease and potential targets for therapeutic intervention. Key nuclear receptors discussed in this review include estrogen-related receptor alpha (ERRα), glucocorticoid receptor (GR), estrogen receptor (ER), liver receptor homolog-1 (LRH-1), and vitamin D receptor (VDR), alongside established nuclear receptors such as peroxisome proliferator-activated receptors (PPARs), farnesoid X receptor (FXR), liver X receptors (LXRs), pregnane X receptor (PXR), hepatocyte nuclear factor 4α (HNF4α), and thyroid hormone receptor beta (THRβ). D Illustration depicting the stages of liver disease progression, starting from fatty liver (steatosis), progressing to steatohepatitis, liver fibrosis, cirrhosis, and potentially hepatocellular carcinoma (HCC).