Xu Yuan, An Ziming, Wang Shufei, Ni Yiming, Zhou Mingmei, Feng Qin, Gou Xiaojun, Xu Meiling, Qi Ying
Department of pharmacology, School of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi 712046, China.
Central Laboratory, Baoshan District Hospital of Integrated Traditional Chinese and Western Medicine of Shanghai, Shanghai University of Traditional Chinese Medicine, Shanghai 201999, China.
Curr Mol Pharmacol. 2023 Oct 13. doi: 10.2174/0118761429259143230927110556.
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.
非酒精性脂肪性肝病（NAFLD）的发病率在全球范围内一直与糖尿病和代谢综合征同步上升。NAFLD指一系列肝脏异常情况，病程各异，从非酒精性脂肪肝（NAFL）到非酒精性脂肪性肝炎（NASH），最终导致肝硬化和肝细胞癌。孕烷X受体（PXR）是核受体超家族的一员，在NAFLD中内源性代谢基因的调控中发挥着重要作用。最近的研究表明，PXR对NAFLD具有治疗潜力，然而PXR与NAFLD之间的关系仍存在争议。在本综述中，提出PXR在NAFLD的发生和发展中起双重作用。其激活会加重肝脏脂肪变性，减轻炎症反应，并预防肝纤维化。此外，还阐明了非酒精性脂肪肝中PXR、物质代谢、炎症、纤维化和肠道微生物群之间的相互作用。由于治疗选择有限，更好地了解PXR对NAFLD发病机制的作用应有助于设计针对NAFLD的创新药物。
