title: The role of fibroblast growth factor 21 in the pathogenesis of non-alcoholic fatty liver disease and implications for therapy.
abstract: Non-alcoholic fatty liver disease (NAFLD) includes a cluster of liver disorders ranging from simple fatty liver to non-alcoholic steatohepatitis (NASH) and cirrhosis. Due to its liver and vascular complications, NAFLD has become a public health problem with high morbidity and mortality. The pathogenesis of NAFLD is considered a "multi-hit hypothesis" that involves lipotoxicity, oxidative stress, endoplasmic reticulum stress, a chronic inflammatory state and mitochondrial dysfunction. Fibroblast growth factor 21 (FGF21) is a member of the fibroblast growth factor family with multiple metabolic functions. FGF21 directly regulates lipid metabolism and reduces hepatic lipid accumulation in an insulin-independent manner. Several studies have shown that FGF21 can ameliorate the "multi-hits" in the pathogenesis of NAFLD. The administration of FGF21 reverses hepatic steatosis, counteracts obesity and alleviates insulin resistance in rodents and nonhuman primates. Using several strategies, we show that the reversal of simple fatty liver and NASH is mediated by activation of the FGF21 signaling pathway. In this review, we describe the molecular mechanisms involved in the onset and/or progression of NAFLD, and review the current literature to highlight the therapeutic procedures associated with the FGF21 signaling pathway for simple fatty liver and NASH, which are the two most important types of NAFLD.
authors.affiliation: Department of Endocrinology, Beijing Chao-yang Hospital, Capital Medical University, No. 8, Gongti South Road, Chaoyang District, Beijing 100020, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Endocrinology, Beijing Chao-yang Hospital, Capital Medical University, No. 8, Gongti South Road, Chaoyang District, Beijing 100020, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Endocrinology, Beijing Chao-yang Hospital, Capital Medical University, No. 8, Gongti South Road, Chaoyang District, Beijing 100020, China.
authors.forename: Yanjin
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Endocrinology, Beijing Chao-yang Hospital, Capital Medical University, No. 8, Gongti South Road, Chaoyang District, Beijing 100020, China. Electronic address: drwg6688@126.com.
authors.forename: Guang
authors.initials: G
authors.lastname: Wang
mesh_terms: D000818:Animals; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*
chemical_list: C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors
keywords: Fibroblast growth factor 21; Insulin resistance; Lipid metabolism; Non-alcoholic fatty liver disease