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

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 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 alpha/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). 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. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.