Effects of sitagliptin on nonalcoholic fatty liver disease in diet-induced obese rats

• Published in: Metabolic syndrome and related disorders Vol. 11; no. 4; p. 243
• Main Authors: Akaslan, Selvihan Beysel, Degertekin, Ceyla Konca, Yilmaz, Guldal, Cakir, Nuri, Arslan, Metin, Toruner, Fusun Balos
• Format: Journal Article
• Language: English
• Published: United States 01-08-2013
• Subjects: Alanine Transaminase - blood; Animals; Blood Glucose - metabolism; Cholesterol - blood; Diet, High-Fat - adverse effects; Dipeptidyl-Peptidase IV Inhibitors - therapeutic use; Fatty Liver - blood; Fatty Liver - drug therapy; Fatty Liver - etiology; Female; Insulin - blood; Insulin Resistance; Liver - drug effects; Liver - metabolism; Liver - pathology; Non-alcoholic Fatty Liver Disease; Obesity - complications; Pyrazines - therapeutic use; Rats; Rats, Sprague-Dawley; Sitagliptin Phosphate; Triazoles - therapeutic use; Triglycerides - blood
• ISSN: 1557-8518
• DOI: 10.1089/met.2012.0128

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.
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.
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).
Sitagliptin may improve hepatic steatosis by increasing insulin sensitivity and improving lipid profiles in rats.