Green Tea Polyphenols Ameliorate the Early Renal Damage Induced by a High‐Fat Diet via Ketogenesis/SIRT3 Pathway

Abstract

Scope Several reports in the literature have suggested the renoprotective effects of ketone bodies and green tea polyphenols (GTPs). Our previous study found that GTP consumption could elevate the renal expression of the ketogenic rate-limiting enzyme, which was decreased by a high-fat diet (HFD) in rats. Here, we investigated whether ketogenesis can mediate renoprotection by GTPs against an HFD. Methods and Results Wistar rats were fed a standard or HFD with or without GTPs for 18 weeks. The renal oxidative stress level, kidney function, renal expression, and activity levels of mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase 2 (HMGCS2) and sirtuin 3(SIRT3) were detected. The increased renal oxidative stress and the loss of renal function induced by the HFD were ameliorated by GTPs. Renal ketogenesis and SIRT3 expression and activity levels, which were reduced by the HFD, were restored by GTPs. In vitro, HEK293 cells were transfected with the eukaryotic expression plasmid pcDNA HMGCS2. GTP treatment could upregulate HMGCS2 and SIRT3 expression. Although SIRT3 expression was not affected by HMGCS2 transfection, the 4-hydroxy-2-nonenal (4-HNE) level and the acetyl-MnSOD (K122)/MnSOD ratio were reduced in HMGCS2-transfected cells in the context of H2O2. Conclusion The ketogenesis/SIRT3 pathway mediates the renoprotection of GTPs against the oxidative stress induced by an HFD.

Lonicera caerulea L. Polyphenols Alleviate Oxidative Stress‐Induced Intestinal Environment Imbalance and Lipopolysaccharide‐Induced Liver Injury in HFD‐Fed Rats by Regulating the Nrf2/HO‐1/NQO1 and MAPK Pathways

“…[ 33 ] The consumption of HFD is one of the main causes of OSD, [ 34 ] which can lead to various pathological symptoms, such as increased bodyweight and colon shortening in rats. [ 35‐37 ] In this study, HFD‐induced OSD rats exhibited a marked increase in bodyweight and a marked decrease in the colon length after consumption of HFD for 8 weeks. Treatment with Vc or LCP decreased the bodyweight and increased the colon length in OSD rats, which indicated that Vc and LCP ameliorate the HFD‐induced intestinal pathology.…”

An 8-Week, Low Carbohydrate, High Fat, Ketogenic Diet Enhanced Exhaustive Exercise Capacity in Mice Part 2: Effect on Fatigue Recovery, Post-Exercise Biomarkers and Anti-Oxidation Capacity

“…However, it is reported that a high-fat diet may induce renal oxidative damage via the ketogenesis/ sirtuin(SIRT)3 pathway, indicating that KD may lead to renal dysfunction [ 8 , 58 ]. Administration of antioxidants seems to be an applicable method to ameliorate this adverse effect [ 59 ].…”

Sirtuins in Renal Health and Disease

“…99 The restoration of renal SIRT3 protein expression and ketogenesis via green tea polyphenols in rats with high fat dietinduced DN have recently been described as limiting early renal oxidative damage. 100…”