Therapeutic effects of the dipeptidyl peptidase-IV inhibitor, sitagliptin, on non-alcoholic steatohepatitis in FLS-ob/ob male mice

  • Authors:
    • Takumi Onoyama
    • Masahiko Koda
    • Toshiaki Okamoto
    • Manabu Kishina
    • Tomomitsu Matono
    • Takaaki Sugihara
    • Yoshikazu Murawaki
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  • Published online on: September 15, 2015     https://doi.org/10.3892/mmr.2015.4329
  • Pages: 6895-6902
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Abstract

Non-alcoholic steatohepatitis is characterized by hepatic fat accumulation, inflammation and varying degrees of fibrosis. The dipeptidyl peptidase‑IV enzyme is important in glucose metabolism, as well as lipid accumulation, extracellular matrix metabolism and immune stimulation. Furthermore, the enzyme activity of dipeptidyl peptidase‑IV is known to be increased in non‑alcoholic steatohepatitis. Therefore, dipeptidyl peptidase‑IV inhibitors are potential therapeutic agents for non‑alcoholic steatohepatitis. The present study assessed the therapeutic effects of sitagliptin, a dipeptidyl peptidase‑IV inhibitor, on non‑alcoholic steatohepatitis using fatty liver Shionogi‑ob/ob male mice. Sitagliptin (2 mg/kg/day; n=10) or placebo (control; n=10) was orally administered to fatty liver Shionogi‑ob/ob mice for 12 weeks, and hepatic steatosis, fibrosis, inflammation and oxidative stress were assessed in comparison with the controls. Sitagliptin administration reduced body weight and blood glucose levels, and improved hepatic fibrosis. It also inhibited the gene expression levels of fatty acid synthase, transforming growth factor‑β1, tissue inhibitor of metalloproteinases‑1, procollagen‑type 1, tumor necrosis factor‑α, monocyte chemoattractant protein‑1 and enhanced peroxisome proliferator activated receptor‑α. Furthermore, a marked attenuation of hepatic stellate cell activation and Kupffer cells was observed in the sitagliptin group. A decrease in oxidative stress and apoptosis was also observed. Sitagliptin attenuated the progression of hepatic fibrosis by improving lipid metabolism, inflammation and oxidative stress in non-alcoholic steatohepatitis.
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November-2015
Volume 12 Issue 5

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Onoyama T, Koda M, Okamoto T, Kishina M, Matono T, Sugihara T and Murawaki Y: Therapeutic effects of the dipeptidyl peptidase-IV inhibitor, sitagliptin, on non-alcoholic steatohepatitis in FLS-ob/ob male mice. Mol Med Rep 12: 6895-6902, 2015
APA
Onoyama, T., Koda, M., Okamoto, T., Kishina, M., Matono, T., Sugihara, T., & Murawaki, Y. (2015). Therapeutic effects of the dipeptidyl peptidase-IV inhibitor, sitagliptin, on non-alcoholic steatohepatitis in FLS-ob/ob male mice. Molecular Medicine Reports, 12, 6895-6902. https://doi.org/10.3892/mmr.2015.4329
MLA
Onoyama, T., Koda, M., Okamoto, T., Kishina, M., Matono, T., Sugihara, T., Murawaki, Y."Therapeutic effects of the dipeptidyl peptidase-IV inhibitor, sitagliptin, on non-alcoholic steatohepatitis in FLS-ob/ob male mice". Molecular Medicine Reports 12.5 (2015): 6895-6902.
Chicago
Onoyama, T., Koda, M., Okamoto, T., Kishina, M., Matono, T., Sugihara, T., Murawaki, Y."Therapeutic effects of the dipeptidyl peptidase-IV inhibitor, sitagliptin, on non-alcoholic steatohepatitis in FLS-ob/ob male mice". Molecular Medicine Reports 12, no. 5 (2015): 6895-6902. https://doi.org/10.3892/mmr.2015.4329