Exendin‑4, a glucagon‑like peptide‑1 receptor agonist, modulates hepatic fatty acid composition and Δ‑5‑desaturase index in a murine model of non‑alcoholic steatohepatitis

Int J Mol Med. 2014 Sep;34(3):782-7. doi: 10.3892/ijmm.2014.1826. Epub 2014 Jun 27.

Abstract

Glucagon‑like peptide‑1 (GLP‑1) is involved in the development of non‑alcoholic steatohepatitis (NASH), which is characterized by fatty acid imbalance. The aim of this study was to investigate the effects of the GLP‑1 receptor (GLP‑1R) agonist, exendin‑4 (Ex‑4), on hepatic fatty acid metabolism and its key enzyme, Δ‑5‑desaturase, in a murine model of NASH. NASH was induced in db/db mice fed a methionine‑choline deficient (MCD) diet. Ex‑4 (n=4) or saline [control (CON); n=4] was administered intraperitoneally for 8 weeks. Steatohepatitis activity was evaluated by non‑alcoholic fatty liver disease (NAFLD) activity score. Hepatic fatty acid composition and Δ‑5‑desaturase index were analyzed by gas chromatography. Ex‑4 treatment significantly reduced body weight and the NAFLD activity score. Hepatic concentrations of long‑chain saturated fatty acids (SFAs) were significantly higher in the Ex‑4 group compared to the CON group (23240±955 vs. 31710±8436 µg/g•liver, P<0.05).Ex‑4 significantly reduced hepatic n‑3 polyunsaturated fatty acid (PUFA)/n‑6 PUFA ratio compared to the CON group (13.83±3.15 vs. 8.73±1.95, P<0.05). In addition, the hepatic Δ‑5‑desaturase index was significantly reduced in the Ex‑4 group compared to the CON group (31.1±12.4 vs. 10.5±3.1, P<0.05). In conclusion, the results showed that Ex‑4 improved steatohepatitis in a murine model of NASH. Furthermore, Ex‑4 altered hepatic long‑chain saturated and PUFA composition and reduced the Δ‑5‑desaturase index. Thus, Ex‑4 may improve NASH by regulating hepatic fatty acid metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Weight / drug effects
  • Delta-5 Fatty Acid Desaturase
  • Disease Models, Animal
  • Exenatide
  • Fatty Acid Desaturases / metabolism*
  • Fatty Acids / metabolism*
  • Glucagon-Like Peptide-1 Receptor
  • Liver / drug effects
  • Liver / enzymology*
  • Liver / pathology
  • Male
  • Mice
  • Models, Biological
  • Non-alcoholic Fatty Liver Disease / drug therapy*
  • Non-alcoholic Fatty Liver Disease / enzymology
  • Non-alcoholic Fatty Liver Disease / pathology*
  • Peptides / pharmacology
  • Peptides / therapeutic use*
  • Receptors, Glucagon / agonists*
  • Receptors, Glucagon / metabolism
  • Triglycerides / metabolism
  • Venoms / pharmacology
  • Venoms / therapeutic use*

Substances

  • Delta-5 Fatty Acid Desaturase
  • Fatty Acids
  • Glp1r protein, mouse
  • Glucagon-Like Peptide-1 Receptor
  • Peptides
  • Receptors, Glucagon
  • Triglycerides
  • Venoms
  • Exenatide
  • Fatty Acid Desaturases