401-P: Effects of Teneligliptin on Lipotoxicity in High-Fat Diet–Induced Diabetic Kidney Disease Model

Lipotoxicity contributes to diabetic kidney disease (DKD), impairing function of glomerulus and podocyte, consequently causing albuminuria. Dipeptidyl peptidase-4 (DPP-4) inhibitors demonstrated renoprotective effects in DKD, but the mechanism for protection in DKD regarding lipid metabolism is unclear. Here, we investigated the effects of teneligliptin in high-fat diet (HFD)-induced DKD model. 5-week-old male C57BL/6J mice were supplemented with HFD for 24 weeks to develop DKD. Teneligliptin was administrated orally by pre-mixing with HFD for 16 weeks. Body weight, blood glucose levels, and glucose and insulin tolerance test were evaluated at 12 weeks and albuminuria was evaluated at 6 and 12 weeks after teneligliptin administration. Lipid panels were evaluated and the renal cortex was collected for histologic examination at 16 weeks. Body weight, random and fasting blood glucose was not significantly different but total cholesterol and triglyceride were reduced in teneligliptin group. Glucose and insulin tolerance test showed significant improvement in teneligliptin group compared with HFD group (p<0.001 and p=0.009, respectively). Changes in albuminuria between 6 and 12 weeks during treatment period group were lower in teneligliptin group compared with HFD group (p=0.07). In immunohistochemistry studies, glomerular volume and mesangial expansion were attenuated in the teneligliptin group by 26.9% and 32.15% respectively (p=0.011 and p=0.043, respectively). Glomerular basement membrane thickness and foot process width were decreased by 43.2% and 9.32% in teneligliptin group (p=0.0007 and p=0.035, respectively). Teneligliptin attenuated diabetic kidney disease in HFD-induced DKD by preserving integrity of glomerulus and podocyte, with decreased albuminuria. Further investigations for detailed mechanisms about the association between DPP-4 inhibitor and lipotoxicity induced glomerulus and podocyte injury in DKD are warranted in the future. Disclosure H.Kim: None. E.Kang: None. R.Kim: None. Y.Yang: None. H.Park: None. N.Jeon: None. M.Lee: None. H.Lee: None. B.Lim: None. H.Choi: None.