Beneficial and deleterious effects of sitagliptin on a methionine/choline-deficient diet-induced steatohepatitis in rats

Non-alcoholic fat liver disease (NAFLD) is the most common chronic liver disease in the world. NAFLD is a spectrum of diseases ranging from simple steatosis to hepatic carcinoma. The complexity of pathomechanisms makes treatment difficult. The oral antidiabetic agents, dipeptidyl peptidase four inhibitors (DPP-4i) have been proposed as possible therapeutic agents. This study was performed using a well-established NAFLD model in rats to elucidate whether sitagliptin could prevent steatohepatitis. Rats were fed a methionine/choline-deficient (MCD) diet with or without sitagliptin treatment for six weeks. Liver tissue was examined to estimate sitagliptin's effect on the development of NASH. The MCD diet decreased the SAM/SAH ratio, and increased plasma levels of homocysteine, free fatty acids, and long-chain acylcarnitines in the MCD rats. MMP2 and Col1A2 expression also increased under the MCD diet. Sitagliptin treatment did not reverse these effects and increased steatosis and long-chain acylcarnitines. In conclusion, sitagliptin was ineffective to prevent from NAFLD in the MCD rat model. This result challenges previous data reporting beneficial effects and is consistent with the clinical trials' negative results. (C) 2021 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved.

Automated summary

NAFLD is a common chronic liver disease, and the study indicates that sitagliptin treatment is not effective in preventing NAFLD development, and may even cause adverse effects in the MCD rat model.