Ohyama T, Sato K, Yamazaki Y, Hashizume H, Horiguchi N, Kakizaki S, Mori M, Kusano M, Yamada M. MK-0626, a selective DPP-4 inhibitor, attenuates hepatic steatosis in ob/ob mice. World J Gastroenterol 2014; 20(43): 16227-16235 [PMID: 25473177 DOI: 10.3748/wjg.v20.i43.16227]
Corresponding Author of This Article
Ken Sato, MD, PhD, Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan. satoken@gunma-u.ac.jp
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Original Article
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Tatsuya Ohyama, Ken Sato, Yuichi Yamazaki, Hiroaki Hashizume, Norio Horiguchi, Satoru Kakizaki, Masatomo Mori, Masanobu Yamada, Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Gunma 371-8511, Japan
Motoyasu Kusano, Department of Endoscopy and Endoscopic Surgery, Gunma University Hospital, Gunma 371-8511, Japan
Author contributions: Sato K designed the research, wrote the paper, and analyzed the data; Ohyama T and Yamazaki Y performed the experiment; Hashizume H, Horiguchi N and Kakizaki S analyzed the data; Mori M and Kusano M revised the draft critically for important intellectual content; Yamada M gave final approval of the version to be published.
Supported by Merck Sharp and Dohme
Correspondence to: Ken Sato, MD, PhD, Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan. satoken@gunma-u.ac.jp
Telephone: +81-27-2208127 Fax: +81-27-2208136
Received: November 13, 2013 Revised: January 6, 2014 Accepted: June 14, 2014 Published online: November 21, 2014 Processing time: 372 Days and 2.8 Hours
Core Tip
Core tip: Administration of MK-0626, a dipeptidyl peptidase-4 inhibitor, ameliorated hepatic steatosis; reduced serum alanine aminotransferase, glucose, and insulin levels; reduced HOMA scores; and increased serum adiponectin levels in ob/ob mice. MK-0626 treatment significantly increased the mRNA expression of peroxisome proliferator-activated receptor α and microsomal triglyceride transfer protein but significantly reduced sterol regulatory element binding transcription factor-1c, fatty acid synthase and stearoyl-CoA desaturase-1. AMP-activated protein kinase (AMPK) activity was significantly increased. These results suggest that MK-0626 could attenuate hepatic steatosis by enhancing AMPK activity, inhibiting hepatic lipogenic gene expression, enhancing triglyceride secretion from the liver and increasing serum adiponectin levels.
