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World J Gastroenterol. Jul 21, 2014; 20(27): 9090-9097
Published online Jul 21, 2014. doi: 10.3748/wjg.v20.i27.9090
Potential roles of glucagon-like peptide-1-based therapies in treating non-alcoholic fatty liver disease
Ye Liu, Rui Wei, Tian-Pei Hong
Ye Liu, Rui Wei, Tian-Pei Hong, Department of Endocrinology and Metabolism, Peking University Third Hospital, Beijing 100191, China
Author contributions: Liu Y collected the data and drafted the article; Wei R revised the article; Hong TP designed the work and supervised the data collection and writing of the article.
Supported by Chinese National 973 Program No. 2012CB517502; and the Research Fund for the Doctoral Program of Higher Education of China No. 20120001120069
Correspondence to: Tian-Pei Hong, MD, PhD, Chief, Department of Endocrinology and Metabolism, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191, China. tpho66@bjmu.edu.cn
Telephone: +86-10-82265515 Fax: +86-10-62017700
Received: December 30, 2013
Revised: March 30, 2014
Accepted: April 30, 2014
Published online: July 21, 2014
Processing time: 203 Days and 6.8 Hours
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.

Keywords: Non-alcoholic fatty liver disease; Glucagon-like peptide-1; Dipeptidyl peptidase-4; Insulin resistance; Oxidative stress; Lipid metabolism

Core tip: Recently, an association of defective glucagon-like peptide-1 (GLP-1) signalling with non-alcoholic fatty liver disease (NAFLD) has been documented. GLP-1-based therapies, which are well accepted in treating diabetes, are effective in improving hepatic endpoints in NAFLD. In addition to the benefits in controlling metabolic disorders, GLP-1-based agents may directly exert actions on the liver through activation of GLP-1 receptors in hepatocytes, resulting in the regulation of gene expression associated with insulin resistance and lipid metabolism, and the suppression of oxidative stress in liver cells. Therefore, GLP-1-based therapies may have potential roles in treating NAFLD.