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  • Sitagliptin reduces insulin resistance and improves rat liver steatosis via the SIRT1/AMPKα pathway.

Sitagliptin reduces insulin resistance and improves rat liver steatosis via the SIRT1/AMPKα pathway.

Experimental and therapeutic medicine (2018-09-15)
Tian Shen, Bilin Xu, Tao Lei, Lin Chen, Cuiping Zhang, Zhenhua Ni
ABSTRACT

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease. It is asymptomatic at presentation and is frequently identified among individuals with metabolic dysfunction, including obesity and diabetes. NAFLD is primarily characterized by the accumulation of triacylglycerol in the liver. Since insulin resistance and fat metabolism dysregulation are major causes of type 2 diabetes and NAFLD, anti-diabetes agents are widely considered as potential therapy strategies for NAFLD. Sitagliptin, an inhibitor of dipeptidyl peptidase-4, has been developed as an oral anti-hyperglycemic agent. In the present study, the effect of sitagliptin on the progression of NAFLD was evaluated in a rat model fed with a high fat diet (HFD). It was identified that sitagliptin significantly suppressed lipid accumulation in rat blood and liver and improved insulin resistance. Furthermore, it was revealed that sitagliptin reactivated the HFD-suppressed SIRT1/AMPK axis pathway and upregulated its downstream target genes, modulating fatty acid metabolism. These findings demonstrate a preventive effect of sitagliptin on hepatic lipid dysregulation and suggest that sitagliptin has potential as a clinical therapeutic strategy for NAFLD.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Serum Triglyceride Determination Kit,  kit sufficient for 250 tests
Sigma-Aldrich
Rat Ins1 / Insulin ELISA Kit