A Low-Protein Calorie-Restricted Diet Attenuates Renal Injury and Facilitates Podocyte Autophagy in Type 2 Diabetic Rats

Abstract

Purpose: Caloric restrictionhas been shown to exert a renoprotective effect in diabetic rats. Dietary protein restriction slows the progression of nephropathy in diabetic patients.We explored whether a low-protein calorie-restricted (LPCR) diet reduces renal injury and whether the renoprotective effect of LPCR diet isrelated to the activation of podocyte autophagy. Methods: The type 2 diabeticrat model was induced by a combination of high fat diet and low dose streptozotocin injection. The diabetic rats were randomly divided into 3 groups, normal protein (NP, 20% protein) group, low protein(LP, 8% protein) group and LPCR (8% protein, 30% restriction)group. Nondiabetic rats were used as normal control (NC). After 4 weeks of dietary intervention, urine albumin-to-creatinine ratio,creatinine clearance, serum creatinine, and kidney-to-body weight ratio, renal histologies, podocyte density, autophagy activity in glomeruli as well as glomerular basement membrane thickness and autophagic vacuoles in podocytesunder electron microscopy were estimated. Results: TheLPCR-diettreated diabetic ratsexhibited reduced body weight, serum triglycerides, and fasting blood glucose levels, as well as improved insulin resistance comparedwith NP-diettreated diabetic rats. LPCR diet attenuated renal injury, includingpodocyte injury, in type 2 diabetic rats. The reduced number of autophagic vacuolesin podocytesand insufficient podocyte autophagyin type 2 diabetic rats were reversed by LPCR diet. Conclusions: The findings suggest that a LPCR diet can ameliorate renal injury in type 2 diabetic rats, which maybe linked to the activation of podocyte autophagy. Disclosure G. Chen: None. Y. Geng: None. C. Liu: None.