The renal protective effect and mechanism of liraglutide in diabetic mice induced by high-fat diet

Abstract

Objective: To investigate the protective effect of liraglutide on kidney of diabetic mice induced by high-fat diet and its possible mechanisms. Methods: C57BL/6J male mice were randomly divided into normal chow diet (NC) group and high-fat diet (HFD) group, which were fed with normal chow diet and HFD for 12 weeks respectively. After diet challenge, the mice were randomly divided into normal control group, normal chow diet with liraglutide treatment (NC+Lira) group, HFD group and high-fat diet with liraglutide treatment (HFD+Lira) group. The mice in NC+Lira and HFD+Lira groups were given intraperitoneal injection of liraglutide (400 μg·kg(-1)·d(-1)) for 8 weeks, while mice in NC and HFD groups were given intraperitoneal injection of same amount of normal saline. Urinary albumin and creatinine levels were measured by enzyme-linked immunosorbent assay (ELISA). Renal morphology was observed by HE staining. The expression levels of silent mating type information regulation 2 homolog 1 (SIRT1) and thioredoxin-interacting protein (TXNIP) were determined by Western blot. Results: Compared with HFD group, liraglutide significantly lowered the body weight [(30.98±1.29) g vs (39.43±2.58) g], fasting blood glucose (FBG) [(7.21±0.15) mmol/L vs (9.55±0.29) mmol/L] and urinary albumin/creatinine ratio (ACR) [(205.48±17.14) μg/mg vs (319.86±34.14) μg/mg] in HFD+Lira group (all P<0.05). HE staining showed that glomerular hypertrophy of HFD group alleviated after liraglutide treatment. The expression level of TXNIP in the kidney of HFD mice significantly decreased after liraglutide treatment (0.41±0.10 vs 3.50±0.70), while expression level of SIRT1 significantly increased (0.75±0.15 vs 0.32±0.04) (both P<0.05). Conclusion: Liraglutide could improve diabetic nephropathy by up-regulation of SIRT1 expression and down-regulation of TXNIP expression in diabetic mice induced by HFD.