title: MK-0626, a selective DPP-4 inhibitor, attenuates hepatic steatosis in ob/ob mice.
abstract: OBJECTIVE
  To investigate the mechanism and in vivo effects of MK-0626, a dipeptidyl peptidase-4 inhibitor, on hepatic steatosis using ob/ob mice.
  
  
  METHODS
  We analyzed obese (ob/ob) 8-wk-old male mice that had been randomly divided into two groups of ob/ob mice (n = 16 each) and were treated with 1.5 or 3 mg/kg MK-0626 and two control groups of untreated ob/ob mice and lean littermates (n = 16 each). All mice were fed a normal chow diet with or without MK-0626 for either four or eight weeks. Blood samples were collected, and total hepatectomy was performed.
  
  
  RESULTS
  The administration of dietary MK-0626 ameliorated the hepatic lipid accumulation in ob/ob mice treated with 3 mg/kg MK-0626 (3 MK), P < 0.05, vs untreated ob/ob mice (ob/ob). The MK-0626 treatment reduced the serum alanine aminotransferase levels (both treatment groups, P < 0.05 vs ob/ob) and glucoses/insulin levels/calculated HOMA scores (1.5 MK, P < 0.05 vs ob/ob; 3 MK, P < 0.01 vs ob/ob) and increased the serum adiponectin levels (3 MK, P < 0.05 vs ob/ob) in a dose-dependent manner. The MK-0626 treatment increased the mRNA expression of peroxisome proliferator-activated receptor α/microsomal triglyceride transfer protein (1.5 MK, P < 0.05 vs ob/ob; 3 MK, P < 0.01 vs ob/ob) but reduced the sterol regulatory element binding transcription factor-1c/fatty acid synthase/stearoyl-CoA desaturase-1 (both treatment groups, P < 0.01 vs ob/ob). The MK-0626 treatment increased the activity of AMP-activated protein kinase (AMPK) (both treatment groups, P < 0.01 vs ob/ob).
  
  
  CONCLUSIONS
  MK-0626 could attenuate hepatic steatosis through enhancing AMPK activity, inhibiting hepatic lipogenic gene expression, enhancing triglyceride secretion from liver and increasing serum adiponectin levels.
authors.affiliation: 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.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ohyama
authors.affiliation: 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.
authors.forename: Ken
authors.initials: K
authors.lastname: Sato
authors.affiliation: 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.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Yamazaki
authors.affiliation: 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.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hashizume
authors.affiliation: 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.
authors.forename: Norio
authors.initials: N
authors.lastname: Horiguchi
authors.affiliation: 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.
authors.forename: Satoru
authors.initials: S
authors.lastname: Kakizaki
authors.affiliation: 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.
authors.forename: Masatomo
authors.initials: M
authors.lastname: Mori
authors.affiliation: 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.
authors.forename: Motoyasu
authors.initials: M
authors.lastname: Kusano
authors.affiliation: 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.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Yamada
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D052242:Adiponectin / Q000097:blood; D000818:Animals; D015415:Biomarkers / Q000097:blood; D019610:Cytoprotection; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005234:Fatty Liver / Q000097:blood / Q000201:enzymology / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D005786:Gene Expression Regulation; D050155:Lipogenesis / Q000187:drug effects / Q000235:genetics; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D008820:Mice, Obese; D009765:Obesity / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014230:Triazoles / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D015415:Biomarkers; D054873:Dipeptidyl-Peptidase IV Inhibitors; C570834:MK0626; D014230:Triazoles; D014280:Triglycerides; D055372:AMP-Activated Protein Kinases; D018819:Dipeptidyl Peptidase 4; C545245:Dpp4 protein, mouse
keywords: AMP-activated protein kinase; Adiponectin; Dipeptidyl peptidase-4 inhibitor; Hepatic steatosis; Microsomal triglyceride transfer protein; ob/ob mice