Protective Effects of Evogliptin on Steatohepatitis in High-Fat-Fed Mice

Abstract

There are few studies on the effects of dipeptidyl peptidase-4 inhibitors on steatohepatitis. We explored whether evogliptin (Evo), a dipeptidyl peptidase-4 inhibitor, protects against steatohepatitis in a high-fat diet (HFD)-fed mice and whether these effects involve modulation of mitophagy. Adult male C57BL/J mice were divided into the normal diet (ND), HFD (45% of energy from fat) with Evo (250 mg/kg) (HFD + Evo), and HFD groups at 4 weeks of age and were sacrificed at 20 weeks of age. The HFD group showed hepatic lipid accumulation; this was decreased in the Evo + HFD group. There was an increased 8-hydroxydeoxyguanosine (8-OHDG) expression in the HFD group compared to ND mice. However, 8-OHDG expression levels were significantly decreased in the HFD + Evo group. Expressions of the mitophagy markers PTEN-induced kinase 1 (PINK1), Parkin, and BNIP-3 (BCL2 Interacting Protein 3) were significantly increased in the HFD group. However, the expressions of these markers were lower in the HFD + Evo group than that in the HFD group. Phospho-Akt was upregulated and p53 was downregulated in the HFD + Evo group compared to the HFD group. Evogliptin may alleviate steatohepatitis in HFD-fed mice by ameliorating steatosis and oxidative stress and by modulating mitophagy in the liver.

Evogliptin, a DPP-4 inhibitor, prevents diabetic cardiomyopathy by alleviating cardiac lipotoxicity in db/db mice

“…We found that EVO treatment reduced blood glucose and HbA1c levels and improved glucose tolerance in db/db mice, consistent with the results of other studies [37][38][39] . However, in our study, EVO did not influence body weight gain, which differs from previous publications that reported that EVO decreased 20 or increased body weight 40 . This difference may be due to the distinct research subjects, the age of the mice, or the dose of EVO.…”

“…Evogliptin® (EVO), a novel DPP-4 inhibitor, was developed by Dong-A, Republic of Korea, and approved as an oral antihyperglycemic drug for the treatment of T2DM by the Ministry of Food and Drug Safety of Korea in 2015. EVO has an effect on gluconeogenesis, hepatic steatosis, vascular inflammation, and whole-body composition [20][21][22][23] . However, the effect of DPP-4 inhibitors on HF is still unknown, and studies on EVO to understand its impact on diabetes and its complications, including DCM, are lacking.…”