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. 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 were 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 / The MK-0626 treatment reduced the serum alanine aminotransferase levels (both treatment groups, P <0.05). The MK-0626 treatment reduced the serum alanine aminotransferase levels (P <0.05) (3 MK, P <0.05 vs ob / ob) and glucoses / insulin levels / calculated HOMA scores (1.5 MK, P <0.05 vs ob / ob; vs ob / ob) in a dose-dependen t manner. MK-0626 treatment increased the m RNA expression of peroxisome proliferator-activated receptor alpha / microsomal triglyceride transfer protein (1.5 MK, P <0.05 vs. ob / 3 MK, P <0.01 vs ob / ob) 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 (both treatment groups, P <0.01 vs ob / ob) .CONCLUSION: MK-0626 could attenuate hepatic steatosis through AMPK activity, inhibiting hepatic lipogenic gene expression, enhancing triglyceride secretion from liver and increasing serum adiponectin levels.