非酒精性脂肪性肝病的治疗方法:既定靶点与药物

Therapeutic Approaches for Nonalcoholic Fatty Liver Disease: Established Targets and Drugs.

作者信息

Huang Xiaojing, Chen Huiling, Wen Song, Dong Meiyuan, Zhou Ligang, Yuan Xinlu

机构信息

Graduate School of Fudan University, Shanghai, People's Republic of China.

Department of Endocrinology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, People's Republic of China.

出版信息

Diabetes Metab Syndr Obes. 2023 Jun 21;16:1809-1819. doi: 10.2147/DMSO.S411400. eCollection 2023.

Abstract

Nonalcoholic fatty liver disease (NAFLD), as a multisystemic disease, is the most prevalent chronic liver disease characterized by extremely complex pathogenic mechanisms and multifactorial etiology, which often develops as a consequence of obesity, metabolic syndrome. Pathophysiological mechanisms involved in the development of NAFLD include diet, obesity, insulin resistance (IR), genetic and epigenetic determinants, intestinal dysbiosis, oxidative/nitrosative stress, autophagy dysregulation, hepatic inflammation, gut-liver axis, gut microbes, impaired mitochondrial metabolism and regulation of hepatic lipid metabolism. Some of the new drugs for the treatment of NAFLD are introduced here. All of them achieve therapeutic objectives by interfering with certain pathophysiological pathways of NAFLD, including fibroblast growth factors (FGF) analogues, peroxisome proliferator-activated receptors (PPARs) agonists, glucagon-like peptide-1 (GLP-1) agonists, G protein-coupled receptors (GPCRs), sodium-glucose cotransporter-2 inhibitors (SGLT-2i), farnesoid X receptor (FXR), fatty acid synthase inhibitor (FASNi), antioxidants, etc. This review describes some pathophysiological mechanisms of NAFLD and established targets and drugs.

摘要

非酒精性脂肪性肝病(NAFLD)作为一种多系统疾病,是最常见的慢性肝病,其致病机制极其复杂,病因多因素,常因肥胖、代谢综合征而发生。NAFLD发生发展涉及的病理生理机制包括饮食、肥胖、胰岛素抵抗(IR)、遗传和表观遗传决定因素、肠道菌群失调、氧化/亚硝化应激、自噬失调、肝脏炎症、肠-肝轴、肠道微生物、线粒体代谢受损以及肝脏脂质代谢调节。本文介绍了一些治疗NAFLD的新药。它们均通过干扰NAFLD的某些病理生理途径来实现治疗目标,包括成纤维细胞生长因子(FGF)类似物、过氧化物酶体增殖物激活受体(PPARs)激动剂、胰高血糖素样肽-1(GLP-1)激动剂、G蛋白偶联受体(GPCRs)、钠-葡萄糖协同转运蛋白2抑制剂(SGLT-2i)、法尼醇X受体(FXR)、脂肪酸合酶抑制剂(FASNi)、抗氧化剂等。本综述描述了NAFLD的一些病理生理机制以及已确定的靶点和药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80f8/10290856/3a79b60aae5f/DMSO-16-1809-g0001.jpg

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