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Exendin4, a glucagonlike peptide1 receptor agonist, modulates hepatic fatty acid composition and Δ5desaturase index in a murine model of nonalcoholic steatohepatitis

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Glucagonlike peptide1 (GLP1) is involved in the development of nonalcoholic steatohepatitis (NASH), which is characterized by fatty acid imbalance. The aim of this study was to investigate the effects of the GLP1 receptor (GLP1R) agonist, exendin4 (Ex4), on hepatic fatty acid metabolism and its key enzyme, Δ5desaturase, in a murine model of NASH. NASH was induced in db/db mice fed a methioninecholine deficient (MCD) diet. Ex4 (n=4) or saline [control (CON); n=4] was administered intraperitoneally for 8 weeks. Steatohepatitis activity was evaluated by nonalcoholic fatty liver disease (NAFLD) activity score. Hepatic fatty acid composition and Δ5desaturase index were analyzed by gas chromatography. Ex4 treatment significantly reduced body weight and the NAFLD activity score. Hepatic concentrations of longchain saturated fatty acids (SFAs) were significantly higher in the Ex4 group compared to the CON group (23240±955 vs. 31710±8436 µg/g•liver, P<0.05).Ex4 significantly reduced hepatic n3 polyunsaturated fatty acid (PUFA)/n6 PUFA ratio compared to the CON group (13.83±3.15 vs. 8.73±1.95, P<0.05). In addition, the hepatic Δ5desaturase index was significantly reduced in the Ex4 group compared to the CON group (31.1±12.4 vs. 10.5±3.1, P<0.05). In conclusion, the results showed that Ex4 improved steatohepatitis in a murine model of NASH. Furthermore, Ex4 altered hepatic longchain saturated and PUFA composition and reduced the Δ5desaturase index. Thus, Ex4 may improve NASH by regulating hepatic fatty acid metabolism.
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Document Type: Research Article

Affiliations: Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume 8300011, Japan

Publication date: January 1, 2014

More about this publication?
  • The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.

    The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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