MK-0626,a selective DPP-4 inhibitor,attenuates hepatic steatosis in ob/ob mice

• Published in: World journal of gastroenterology : WJG Vol. 20; no. 43; pp. 16227 - 16235
• Main Authors: Ohyama, Tatsuya, Sato, Ken, Yamazaki, Yuichi, Hashizume, Hiroaki, Horiguchi, Norio, Kakizaki, Satoru, Mori, Masatomo, Kusano, Motoyasu, Yamada, Masanobu
• Format: Journal Article
• Language: English
• Published: United States Baishideng Publishing Group Inc 21.11.2014
• Subjects: Adiponectin - blood; AMP-Activated Protein Kinases - metabolism; Animals; Biomarkers - blood; Cytoprotection; Dipeptidyl; Dipeptidyl Peptidase 4 - metabolism; Dipeptidyl-Peptidase IV Inhibitors - pharmacology; Disease Models, Animal; Dose-Response Relationship, Drug; Enzyme Activation; Fatty Liver - blood; Fatty Liver - enzymology; Fatty Liver - etiology; Fatty Liver - genetics; Fatty Liver - pathology; Fatty Liver - prevention & control; Gene Expression Regulation; Hepatic; inhibitor; Lipogenesis - drug effects; Lipogenesis - genetics; Liver - drug effects; Liver - enzymology; Liver - pathology; Male; Mice, Obese; Obesity - blood; Obesity - complications; Obesity - drug therapy; Obesity - enzymology; Obesity - genetics; Original; peptidase-4; Signal Transduction - drug effects; steatosis; Time Factors; Triazoles - pharmacology; Triglycerides - blood; Microsomal triglyceride transfer protein; Dipeptidyl peptidase-4 inhibitor; ob/ob mice; Hepatic steatosis; AMP-activated protein kinase; Adiponectin
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v20.i43.16227

AIM: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 with1.5 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 micetreated 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<0.05vs 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 m RNA expression of peroxisome proliferator-activated receptorα/microsomal triglyceride transfer protein(1.5 MK,P<0.05 vs ob/ob;3 MK,P<0.01vs ob/ob)but reduced the sterol regulatory element binding transcription factor-1c/fatty acid synthase/stearoyl-Co A 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).CONCLUSION: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.