The glucagon-like peptide-1 receptor agonist Exendin 4 has a protective role in ischemic injury of lean and steatotic liver by inhibiting cell death and stimulating lipolysis.

Journal Article (Journal Article)

Nonalcoholic fatty liver disease is an increasingly prevalent spectrum of conditions characterized by excess fat deposition within hepatocytes. Affected hepatocytes are known to be highly susceptible to ischemic insults, responding to injury with increased cell death, and commensurate liver dysfunction. Numerous clinical circumstances lead to hepatic ischemia. Mechanistically, specific means of reducing hepatic vulnerability to ischemia are of increasing clinical importance. In this study, we demonstrate that the glucagon-like peptide-1 receptor agonist Exendin 4 (Ex4) protects hepatocytes from ischemia reperfusion injury by mitigating necrosis and apoptosis. Importantly, this effect is more pronounced in steatotic livers, with significantly reducing cell death and facilitating the initiation of lipolysis. Ex4 treatment leads to increased lipid droplet fission, and phosphorylation of perilipin and hormone sensitive lipase - all hallmarks of lipolysis. Importantly, the protective effects of Ex4 are seen after a short course of perioperative treatment, potentially making this clinically relevant. Thus, we conclude that Ex4 has a role in protecting lean and fatty livers from ischemic injury. The rapidity of the effect and the clinical availability of Ex4 make this an attractive new therapeutic approach for treating fatty livers at the time of an ischemic insult.

Full Text

Duke Authors

Cited Authors

  • Gupta, NA; Kolachala, VL; Jiang, R; Abramowsky, C; Romero, R; Fifadara, N; Anania, F; Knechtle, S; Kirk, A

Published Date

  • November 2012

Published In

Volume / Issue

  • 181 / 5

Start / End Page

  • 1693 - 1701

PubMed ID

  • 22960075

Pubmed Central ID

  • PMC5691335

Electronic International Standard Serial Number (EISSN)

  • 1525-2191

Digital Object Identifier (DOI)

  • 10.1016/j.ajpath.2012.07.015


  • eng

Conference Location

  • United States