Dual Role of Pregnane X Receptor in Nonalcoholic Fatty Liver Disease

Yuan Xu; Ziming An; Shufei Wang; Yiming Ni; Mingmei Zhou; Qin Feng; Xiaojun Gou; Meiling Xu; Ying Qi

doi:10.2174/0118761429259143230927110556

Dual Role of Pregnane X Receptor in Nonalcoholic Fatty Liver Disease

Curr Mol Pharmacol. 2023 Oct 13. doi: 10.2174/0118761429259143230927110556. Online ahead of print.

Authors

Yuan Xu^{1

2}, Ziming An³, Shufei Wang^{1

2}, Yiming Ni⁴, Mingmei Zhou⁴, Qin Feng³, Xiaojun Gou², Meiling Xu⁵, Ying Qi⁶

Affiliations

¹ Department of pharmacology, School of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi 712046, China.
² Central Laboratory, Baoshan District Hospital of Integrated Traditional Chinese and Western Medicine of Shanghai, Shanghai University of Traditional Chinese Medicine, Shanghai 201999, China.
³ Institute of Liver Disease, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
⁴ Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
⁵ Chongqing Emergency Medical Center, Chongqing University Central Hospital, Chongqing, 400014, China.
⁶ School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, 311121, China.

PMID: 37936450
DOI: 10.2174/0118761429259143230927110556

Abstract

The incidence of nonalcoholic fatty liver disease (NAFLD) has been rising worldwide in parallel with diabetes and metabolic syndrome. NAFLD refers to a spectrum of liver abnormalities with a variable course, ranging from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), eventually leading to cirrhosis and hepatocellular carcinoma. Pregnane X receptor (PXR), a member of the nuclear receptor superfamily, plays a prominent part in the regulation of endogenous metabolic genes in NAFLD. Recent studies have suggested that PXR has therapeutic potential for NAFLD, yet the relationship between PXR and NAFLD remains controversial. In this review, PXR is proposed to play a dual role in the development and progression of NAFLD. Its activation will aggravate steatosis of the liver, reduce inflammatory response, and prevent liver fibrosis. In addition, the interactions between PXR, substance metabolism, inflammation, fibrosis, and gut microbiota in non-alcoholic fatty liver were elucidated. Due to limited therapeutic options, a better understanding of the contribution of PXR to the pathogenesis of NAFLD should facilitate the design of innovative drugs targeting NAFLD.

Keywords: Metabolism.; Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis; Nuclear receptor; Pregnane X receptor (PXR).