Lei Kaiwen, Chen Yan, Wu Jianxing, Lin Yiyu, Bai Yan, Cao Hua, Che Qishi, Guo Jiao, Su Zhengquan
Guangdong Engineering Research Center of Natural Products and New Drugs, Guangdong Provincial University Engineering Technology Research Center of Natural Products and Drugs, Guangdong Pharmaceutical University, Guangzhou 510006, China; Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Guangdong TCM Key Laboratory for Metabolic Diseases, Guangdong Pharmaceutical University, Guangzhou 510006, China.
School of Public Health, Guangdong Pharmaceutical University, Guangzhou 510310, China.
Int J Biol Macromol. 2025 May;307(Pt 4):142275. doi: 10.1016/j.ijbiomac.2025.142275. Epub 2025 Mar 18.
Metabolism associated fatty liver disease (MAFLD) has emerged as a growing global health challenge with limited effective treatments. Research on nuclear receptors offers promising new therapeutic avenues for MAFLD. The liver X receptor (LXR) has gained attention for its roles in tumors and metabolic and inflammatory diseases; However, its effects on MAFLD treatment remain a subject of debate. This review explores the therapeutic role of LXRα in MAFLD, focusing on its functions in the intestine, hepatic and adipose tissue, and summarizes recent advancements in LXRα ligands over the past five years. In the intestine, LXRα activation enhances the efflux of non-biliary cholesterol and reduces inflammation in the gut-liver axis by regulating intestinal high-density lipoprotein synthesis and its interaction with lipopolysaccharide. In the liver, LXRα activation facilitates cholesterol transport, influences hepatic lipid synthesis, and exerts anti-inflammatory effects. In adipose tissue, LXRα helps delay MAFLD progression by managing lipid autophagy and insulin resistance. Ligands that modulate LXRα transcriptional activity show considerable promise for MAFLD treatment.
代谢相关脂肪性肝病（MAFLD）已成为一个日益严峻的全球健康挑战，有效治疗方法有限。对核受体的研究为MAFLD提供了有前景的新治疗途径。肝脏X受体（LXR）因其在肿瘤、代谢和炎症性疾病中的作用而受到关注；然而，其对MAFLD治疗的影响仍存在争议。本综述探讨了LXRα在MAFLD中的治疗作用，重点关注其在肠道、肝脏和脂肪组织中的功能，并总结了过去五年中LXRα配体的最新进展。在肠道中，LXRα激活可增强非胆汁胆固醇的流出，并通过调节肠道高密度脂蛋白合成及其与脂多糖的相互作用来减轻肠-肝轴炎症。在肝脏中，LXRα激活促进胆固醇转运，影响肝脏脂质合成，并发挥抗炎作用。在脂肪组织中，LXRα通过管理脂质自噬和胰岛素抵抗来帮助延缓MAFLD的进展。调节LXRα转录活性的配体在MAFLD治疗方面显示出相当大的前景。
