Protective effect of metformin on renal injury of C57BL/6J mouse treated with high fat diet.

ABSTRACT

This study aimed to investigate the protective effect of metformin on renal injury of C57BL/6J mice treated with a high fat diet. High-fat diet for 12 weeks was used to establish the mice model of metabolism syndrome and the intervention of metformin (75 mg x kg(-1) x d(-1)) for 4 weeks, and plasma biochemical indicator and body weight were used to evaluate the model. Sterol regulatory element-binding protein (SERBP)-1c, TNF-α, NADPH Oxidase (NOX)4 mRNA was determined by real time-PCR. Phospho-AMP-activated protein kinase (P-AMPK)α protein was detected by western blotting. Oil Red O staining, Masson staining and HE staining were for observing renal pathological changes. At the end of 12th week, compared with mice on low fat diet (LFD), body weight (BW), the levels of fasting insulin (FINS), plasma and renal triglyceride (TG) were higher and plasma high density lipoprotein (HDL) and insulin sensitivity index (ISI) were significantly lower, but the levels of fasting blood glycemia (FBG), plasma total cholesterol (TC) and renal TC had no changes; Oil Red O staining revealed renal lipids deposition, Masson staining and HE staining revealed glomerular hypertrophy, matrix increasing, and inflammatory cells infiltration in glomerular; the expression of p-AMPKα protein decreased and the expression of SREBP-1c, TNF-α, NOX4 mRNA increased significantly in mouse treated with high fat diet (HFD). Compared with the HFD group, through metformin interventing, metabolic disorders were significantly improved, renal lipids deposition and other pathological changes were ameliorated, the expression of p-AMPKα protein increased and the expression of SREBP-1c, TNF-α, NOX4 mRNA decreased significantly. Metformin improved metabolic disorders, upregulated activity of renal AMPK, diminished the expression of renal SREBP-1c, TNF-α, NOX4 mRNA, decreased accumulation of renal lipids, and prevened renal injury.