Onoyama_2015_Mol.Med.Rep_12_6895

Reference

Title : Therapeutic effects of the dipeptidyl peptidase-IV inhibitor, sitagliptin, on non-alcoholic steatohepatitis in FLS-ob\/ob male mice - Onoyama_2015_Mol.Med.Rep_12_6895
Author(s) : Onoyama T , Koda M , Okamoto T , Kishina M , Matono T , Sugihara T , Murawaki Y
Ref : Mol Med Rep , 12 :6895 , 2015
Abstract :

Non-alcoholic steatohepatitis is characterized by hepatic fat accumulation, inflammation and varying degrees of fibrosis. The dipeptidyl peptidaseIV enzyme is important in glucose metabolism, as well as lipid accumulation, extracellular matrix metabolism and immune stimulation. Furthermore, the enzyme activity of dipeptidyl peptidaseIV is known to be increased in nonalcoholic steatohepatitis. Therefore, dipeptidyl peptidaseIV inhibitors are potential therapeutic agents for nonalcoholic steatohepatitis. The present study assessed the therapeutic effects of sitagliptin, a dipeptidyl peptidaseIV inhibitor, on nonalcoholic steatohepatitis using fatty liver Shionogiob/ob male mice. Sitagliptin (2 mg/kg/day; n=10) or placebo (control; n=10) was orally administered to fatty liver Shionogiob/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 factorbeta1, tissue inhibitor of metalloproteinases1, procollagentype 1, tumor necrosis factoralpha, monocyte chemoattractant protein1 and enhanced peroxisome proliferator activated receptoralpha. 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.

PubMedSearch : Onoyama_2015_Mol.Med.Rep_12_6895
PubMedID: 26397061

Related information

Inhibitor Sitagliptin

Citations formats

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
Mol Med Rep 12 :6895

Onoyama T, Koda M, Okamoto T, Kishina M, Matono T, Sugihara T, Murawaki Y (2015)
Mol Med Rep 12 :6895