title: Effects of sitagliptin on nonalcoholic fatty liver disease in diet-induced obese rats.
abstract: BACKGROUND
  Studies investigating the effects of dipeptidyl peptidase-4 inhibitors on hepatic steatosis are lacking. We aimed to determine the effects of sitagliptin on nonalcoholic fatty liver disease (NAFLD) in rats with diet-induced obesity.
  
  
  METHODS
  A total of 24 adult female Sprague-Dawley rats, which were 24 weeks old and weighed 199-240 grams, were used. The rats were randomly separated into two groups. The control group (n=6) was fed with standard rat diet; the remaining rats (n=18) were fed with a high-fat diet (HFD) to induce NAFLD. After 12 weeks, rats that were fed with a HFD were randomly separated into two groups: (1) HFD-only group (n=8) was fed with a HFD for an additional 4 weeks, (2) HFD-sitagliptin group (n=10) received sitagliptin (3 mg/kg) for 4 weeks in addition to HFD. At the end of the study (16(th) week), blood samples were drawn from all rats to determine serum glucose, triglyceride, cholesterol, alanine aminotransferase (ALT), and plasma insulin levels. Insulin resistance was determined using the homeostasis model assessment of insulin resistance (HOMA-IR) index. Histopathologic evaluation of liver samples was undertaken.
  
  
  RESULTS
  The HFD-sitagliptin group had significantly lower serum glucose (140.8±18.8 vs. 224.7±20.6 mg/dL, P<0.001), plasma insulin (15.8±4.4 vs. 28.0±5.9 μIU/L, P<0.001), HOMA-IR index (4.9±1.8 vs. 15.9±2.3, P<0.001), serum triglycerides (199.0±108.7 vs. 468.0±370.7 mg/dL, P<0.001), and cholesterol (82.0±26.7 vs. 90.5±7.0, P<0.001) values compared to the HFD-only group. Hepatic steatosis was significantly less (mean score, 1 vs. 2; P<0.001) in the HFD-sitagliptin group compared to the HFD-only group, whereas there was no difference in hepatic inflammation (P=0.057), liver weight (P=0.068), and ALT levels (P=0.232).
  
  
  CONCLUSIONS
  Sitagliptin may improve hepatic steatosis by increasing insulin sensitivity and improving lipid profiles in rats.
authors.affiliation: Department of Internal Medicine, Gazi University Faculty of Medicine, Ankara, Turkey.
authors.forename: Selvihan Beysel
authors.initials: SB
authors.lastname: Akaslan
authors.forename: Ceyla Konca
authors.initials: CK
authors.lastname: Degertekin
authors.forename: Guldal
authors.initials: G
authors.lastname: Yilmaz
authors.forename: Nuri
authors.initials: N
authors.lastname: Cakir
authors.forename: Metin
authors.initials: M
authors.lastname: Arslan
authors.forename: Fusun Balos
authors.initials: FB
authors.lastname: Toruner
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D005234:Fatty Liver / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D065626:Non-alcoholic Fatty Liver Disease; D009765:Obesity / Q000150:complications; D011719:Pyrazines / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007328:Insulin; D011719:Pyrazines; D014230:Triazoles; D014280:Triglycerides; D002784:Cholesterol; D000410:Alanine Transaminase; D000068900:Sitagliptin Phosphate