title: Potential roles of glucagon-like peptide-1-based therapies in treating non-alcoholic fatty liver disease.
abstract: Glucagon-like peptide-1 (GLP-1)-based therapies have demonstrated efficacy and safety in treating type 2 diabetes, which shares a similar pathophysiological mechanism with non-alcoholic fatty liver disease (NAFLD). Recent studies showed that glucose-induced GLP-1 secretion was decreased in patients with NAFLD and that the level of dipeptidyl peptidase-4, which inactivates intact GLP-1, was upregulated. Moreover, the expression of the GLP-1 receptor was downregulated in livers from patients with NAFLD, indicating an association of defective GLP-1 signalling with NAFLD. Notably, GLP-1-based therapies are reported to be effective in improving hepatic endpoints in patients with NAFLD, such as reducing hepatic fat content, hepatic steatosis and plasma transaminase levels, and preventing fibrosis. GLP-1-based therapies are beneficial for body weight control and glycaemic normalisation, which are important for the management of NAFLD. Moreover, clinical and preclinical studies showed that GLP-1-based agents might directly exert their actions on the liver through activation of functional GLP-1 receptors in hepatocytes. The possible mechanisms involve regulating gene expression that is associated with insulin resistance and lipid metabolism, and suppressing oxidative stress in the liver cells, thus preventing the development and progression of NAFLD. Based on these promising data, large-scale randomised controlled trials are warranted to assess the efficacy and safety of GLP-1-based therapies in treating NAFLD.
authors.affiliation: Ye Liu, Rui Wei, Tian-Pei Hong, Department of Endocrinology and Metabolism, Peking University Third Hospital, Beijing 100191, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Ye Liu, Rui Wei, Tian-Pei Hong, Department of Endocrinology and Metabolism, Peking University Third Hospital, Beijing 100191, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wei
authors.affiliation: Ye Liu, Rui Wei, Tian-Pei Hong, Department of Endocrinology and Metabolism, Peking University Third Hospital, Beijing 100191, China.
authors.forename: Tian-Pei
authors.initials: TP
authors.lastname: Hong
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D054795:Incretins / Q000627:therapeutic use*; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D018384:Oxidative Stress / Q000187:drug effects; D018027:Receptors, Glucagon / Q000819:agonists* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D000975:Antioxidants; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D054795:Incretins; D018027:Receptors, Glucagon; D052216:Glucagon-Like Peptide 1
keywords: Dipeptidyl peptidase-4; Glucagon-like peptide-1; Insulin resistance; Lipid metabolism; Non-alcoholic fatty liver disease; Oxidative stress
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