CONICET | Buscador de Institutos y Recursos Humanos

Chronic inflammation is a common feature of obesity, insulin-resistance and dyslipidemia, conditions that contribute to the development of chronic kidney disease. The flavanol (−)-epicatechin (EC) is present in the human diet. In human and animal studies EC consumption was associated with a range of health benefits. The aim of this work was to characterize the mechanisms involved in the prevention or attenuation by EC of kidney inflammation in mice fed a high-fat (HF) diet. C57BL/6J male mice were divided into 4 groups: control (C), control + 20 mg EC/kg body weight (CE), HF diet (60% fat from lard), and HF diet + EC (HFE) for 14 w. Body weight was higher in the HF and HFE mice compared to both control groups. EC supplementation mitigated the hyperglycemia and dyslipidemia developed by HF mice. High-fat fed mice showed increased kidney cortex vacuolization, that was not affected by EC. Consumption of the high-fat diet led to endotoxemia, increased expression of kidney TLR4 (73% over control values), MyD88 (62% over control values), and AP-1-DNA binding measured by EMSA in nuclear fractions (78% over control values). EC supplementation prevented all these increases. Furthermore, the increase in AP-1 activity in the HF group was not induced by the mitogen-activated protein kinases ERK and JNK. HF mice showed an overexpression of TGFβ-1 in kidney cortex respect to C and HFE groups. The Nrf2 pathway and the activation of NF-κB and HIF-1 were not affected by any of the treatments. In this model of obesity, mice developed kidney inflammation with evidence of fibrosis, which were both mitigated by EC. Inflammation was indicated by an increased expression of TLR4, accompanied by the activation of the MyD88/AP-1 pathway, which was not observed in HFE group. In summary, dietary EC can protect the kidneys from the inflammatory damage associated with consumption of high fat diets and obesity.