The Dipeptidyl Peptidase-4 Inhibitor Teneligliptin Attenuates Hepatic Lipogenesis via AMPK Activation in Non-Alcoholic Fatty Liver Disease Model MiceReportar como inadecuado




The Dipeptidyl Peptidase-4 Inhibitor Teneligliptin Attenuates Hepatic Lipogenesis via AMPK Activation in Non-Alcoholic Fatty Liver Disease Model Mice - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

1

Department of Gastroenterology, Internal Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan

2

Informative Clinical Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan





*

Author to whom correspondence should be addressed.



Academic Editor: Amedeo Lonardo

Abstract Non-alcoholic fatty liver disease NAFLD, which is strongly associated with metabolic syndrome, is increasingly a major cause of hepatic disorder. Dipeptidyl peptidase DPP-4 inhibitors, anti-diabetic agents, are expected to be effective for the treatment of NAFLD. In the present study, we established a novel NAFLD model mouse using monosodium glutamate MSG and a high-fat diet HFD and investigated the effects of a DPP-4 inhibitor, teneligliptin, on the progression of NAFLD. Male MSG-HFD-treated mice were divided into two groups, one of which received teneligliptin in drinking water. Administration of MSG and HFD caused mice to develop severe fatty changes in the liver, but teneligliptin treatment improved hepatic steatosis and inflammation, as evaluated by the NAFLD activity score. Serum alanine aminotransferase and intrahepatic triglyceride levels were significantly decreased in teneligliptin-treated mice p < 0.05. Hepatic mRNA levels of the genes involved in de novo lipogenesis were significantly downregulated by teneligliptin p < 0.05. Moreover, teneligliptin increased hepatic expression levels of phosphorylated AMP-activated protein kinase AMPK protein. These findings suggest that teneligliptin attenuates lipogenesis in the liver by activating AMPK and downregulating the expression of genes involved in lipogenesis. DPP-4 inhibitors may be effective for the treatment of NAFLD and may be able to prevent its progression to non-alcoholic steatohepatitis. View Full-Text

Keywords: AMPK; DPP-4 inhibitor; lipogenesis; non-alcoholic fatty liver disease; NAFLD; SREBP1c; teneligliptin AMPK; DPP-4 inhibitor; lipogenesis; non-alcoholic fatty liver disease; NAFLD; SREBP1c; teneligliptin





Autor: Takayasu Ideta 1, Yohei Shirakami 1,2,* , Tsuneyuki Miyazaki 1, Takahiro Kochi 1, Hiroyasu Sakai 1, Hisataka Moriwaki 1 and Masahito Shimizu 1

Fuente: http://mdpi.com/



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