Proinflammatory and antioxidant signaling pathways in kidney of high-fat fed mice: effect of (-)-epicatechin dietary administration

LITTERIO MC; FISCHERMAN L; CREMONINI E; OTEIZA PI; GALLEANO M; FRAGA CG

Congreso; 9th International Conference on Polyphenols and Health; 2019

ICPH

or attenuation of kidney inflammation and oxidative stress provided by dietary (-)-epicatechin (EC)in mice fed a high-fat diet.Materials and Methods: C57BL/6J male mice were fed for 14 w control (C) or high-fat diets(60% fat from lard), without (HF) or with 20 mg EC/kg body weight (HFE). At the end of thestudy, kidneys were isolated and the kidney cortex processed for IHC, to obtain total and nuclearfractions, and for mRNA isolation.Results: After 14 w on the high fat diet, body weight was higher in the HF and HFE mice (46.8±0.9 and 47.4 ±1.0 g, respectively) compared to both control groups (36.9 ±0.7 and 36.3 ±0.8 g, forC and CE groups respectively). HF mice developed hyperglycemia and dyslipidemia, which wereboth mitigated by EC supplementation. High-fat fed mice showed increased kidney cortexvacuolization, compatible with an augmentation in lipid deposition that was not affected by EC.Consumption of the high-fat diet led to endotoxemia, increased expression of kidney TLR4receptor (73% over control values), MyD88 (62% over control values) (evaluated by Western blot),and AP-1-DNA binding measured by EMSA in nuclear fractions (78% over control values). ECsupplementation prevented all these increases. The expression of TGFβ 1, evaluated by IHC inkidney cortex of HF mice were 15-fold higher than in C mice, while only a 5-fold increase over theC group was observed in the EC-supplemented mice. The activation of NF-κB and HIF-1(measured as their DNA-binding activity in nuclear fractions) was not affected by high-fat dietconsumption. In terms of antioxidant defenses, the Nrf2 pathway was not affected in HF mice, asevidenced by both EMSA assays and by the unaffected expression of Nrf2-dependent genes, i.e.glutamate-cysteine ligase modulatory and catalytic subunits, and peroxirredoxin 1.Conclusions: In a model of high fat diet-induced obesity mice developed kidney inflammationwith evidence of fibrosis, which were both mitigated by EC. Inflammation was indicated by anincreased expression of TLR4, accompanied by the activation of the MyD88/AP-1 pathway, whichwas not observed when mice were supplemented with dietary EC. In summary, dietary EC canprotect the kidneys from the inflammatory damage associated with consumption of high fat dietsand obesity.