Diabetes Metab J.  2012 Aug;36(4):262-267. 10.4093/dmj.2012.36.4.262.

GLP-1 Receptor Agonist and Non-Alcoholic Fatty Liver Disease

• Lee J
• Hong SW
• Rhee EJ
• Lee WY

• KMID: 2174417
• DOI: http://doi.org/10.4093/dmj.2012.36.4.262

Abstract

Non-alcoholic fatty liver disease (NAFLD), one of the most common liver diseases, is caused by the disruption of hepatic lipid homeostasis. It is associated with insulin resistance as seen in type 2 diabetes mellitus. Glucagon-like peptide-1 (GLP-1) is an incretin that increases insulin sensitivity and aids glucose metabolism. In recent in vivo and in vitro studies, GLP-1 presents a novel therapeutic approach against NAFLD by increasing fatty acid oxidation, decreasing lipogenesis, and improving hepatic glucose metabolism. In this report, we provide an overview of the role and mechanism of GLP-1 in relieving NAFLD.

Keyword

Fatty acid oxidation; Glucagon-like peptide 1; Non-alcoholic fatty liver disease

MeSH Terms

Diabetes Mellitus, Type 2
Fatty Liver
Glucagon-Like Peptide 1
Glucose
Homeostasis
Incretins
Insulin Resistance
Lipogenesis
Liver Diseases
Receptors, Glucagon
Fatty Liver
Glucagon-Like Peptide 1
Glucose
Incretins
Receptors, Glucagon

Figure

• 

  Fig. 1 Proposed regulatory mechanisms between silent mating type information regulation 2 homolog (SIRT1) and AMP-activated protein kinase (AMPK). (A) Activation of SIRT by activator leads to deacetylation of Lys48 residues on LKB1. LKB1 moves to the cytoplasm and then, phosphorylates and activates the AMPK. (B) The enhancement of AMP/ATP ratio stimulates AMPK activity. Activated AMPK regulates SIRT1, an NAD+-dependent protein deacetylase, by increasing NAD+ levels. NAM, nicotinamide; NAMPT, nicotinamide phosphoribosyltransferase (Adapted from Cantó et al., Curr Opin Lipidol 2009;20:98-105 [29]).

• 

  Fig. 2 Regulation of glucagon-like peptide-1 receptor (GLP-1R), SIRT1 and AMPK by exendin-4 (Ex-4) in HepG2 and Huh7 cells. (A) Cells were treated with 50, 100, or 500 nM Ex-4 for 24 hours. GLP-1R and β-actin were measured by western blot and real-time PCR. GLP-1R was normalized to β-actin. (B) Cells given 0.4 mM palmitic acid (PA) were treated with either vehicle or 50 to 100 nM Ex-4 for 24 hours. (C) Cells given 0.4 mM palmitic acid were treated with 100 nM Ex-4 in the absence or presence of 10 mM nicotinamide (NAM) or 10 µM compound C (CC) for 24 hours. (B, C) SIRT1, phosphorylated AMPKα at threonine 172, AMPK, and β-actin were measured by Western blot in HepG2 cells. SIRT1 and phosphorylated AMPKα were normalized to the β-actin and total AMPKα of each sample, respectively. aP<0.05, bP<0.01 compared with control, cP<0.05, compared with PA, and dP<0.05 compared with Ex-4 (Adapted from Lee J, et al. PLoS One 2012;7:e31394 [19]).

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