The role of the retinoid receptor, RAR/RXR heterodimer, in liver physiology

Activated by retinoids, metabolites of vitamin A, the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs) play important roles in a wide variety of biological processes, including embryo development, homeostasis, cell proliferation, differentiation and death. In this review, we summarized the functional roles of nuclear receptor RAR/RXR heterodimers in liver physiology. Specifically, RAR/RXR modulate the synthesis and metabolism of lipids and bile acids in hepatocytes, regulate cholesterol transport in macrophages, and repress fibrogenesis in hepatic stellate cells. We have also listed the specific genes that carry these functions and how RAR/RXR regulate their expression in liver cells, providing a mechanistic view of their roles in liver physiology. Meanwhile, we pointed out many questions regarding the detailed signaling of RAR/RXR in regulating the expression of liver genes, and hope future studies will address these issues. •RAR/RXR stimulates expression of FGF21 and FGF19, leading to increased fatty acid oxidation and reduced levels of NEFA and TG.•RAR/RXR modulates bile acid homeostasis by regulating the expression of genes involved in bile acid synthesis and transport.•RAR/RXR represses liver fibrosis by blocking hepatic stellate cell activation and proliferation.•RAR/RXR accelerates lipid metabolism in macrophages by stimulating cholesterol transport.