Green Tea Polyphenols, Mimicking the Effects of Dietary Restriction, Ameliorate High-Fat Diet-Induced Kidney Injury via Regulating Autophagy Flux

Epidemiological and experimental studies reveal that Western dietary patterns contribute to chronic kidney disease, whereas dietary restriction (DR) or dietary polyphenols such as green tea polyphenols (GTPs) can ameliorate the progression of kidney injury. This study aimed to investigate the renal protective effects of GTPs and explore the underlying mechanisms. Sixty Wistar rats were randomly divided into 6 groups: standard diet (STD), DR, high-fat diet (HFD), and three diets plus 200 mg/kg(bw)/day GTPs, respectively. After 18 weeks, HFD group exhibited renal injuries by increased serum cystatin C levels and urinary N-acetyl-β-d-glucosaminidase activity, which can be ameliorated by GTPs. Meanwhile, autophagy impairment as denoted by autophagy-lysosome related proteins, including LC3-II, Beclin-1, p62, cathepsin B, cathepsin D and LAMP-1, was observed in HFD group, whereas DR or GTPs promoted renal autophagy activities and GTPs ameliorated HFD-induced autophagy impairment. In vitro, autophagy flux suppression was detected in palmitic acid (PA)-treated human proximal tubular epithelial cells (HK-2), which was ameliorated by epigallocatechin-3-gallate (EGCG). Furthermore, GTPs (or EGCG) elevated phosphorylation of AMP-activated protein kinase in the kidneys of HFD-treated rats and in PA-treated HK-2 cells. These findings revealed that GTPs mimic the effects of DR to induce autophagy and exert a renal protective effect by alleviating HFD-induced autophagy suppression.