(-)-Epicatechin mitigates insulin resistance by modulating redox-sensitive signals in animal models of metabolic syndrome

CREMONINI, E; BETTAIEB, A; VAZQUEZ PRIETO, MA; BILLIARD, L; HAJ, FG; FRAGA, CG; OTEIZA, PI

Davis

Congreso; Oxidants and Antioxidants in Biology: Nutrition and Redox Biology in Development and Health; 2014

Oxygen Club of California

The incidence of metabolic syndrome (MetS) in the wordl`s adults population is becoming a major public health concern. Epidemiological studies show that consumption of fruit and vegetables in humans decrease the risk for MetS. The flavan-3-ol (-)-epicatechin (EC) is present in large amounts in fruit and vegetables. We previously showed that EC improves parameters of inflammation and insulin sensitivity in adipocytes in vitro. The aim of this study was to investigate, in vivo models of MetS, the capacity of dietary EC to improve insulin sensitivity and the involvement of redox-sensitive signals underlying MetS-induced insulin rsistance. The effects of dietary EC (20 mg/Kg body weight) on the above parameters were assessed in two rodent model: A-MetS induced by high fructose (HFr) consumption in rats; B-MetS-induced by high fat (HFat) consumption in mice. After 8 w, although glucose (GTT) and insulin (ITT) tolerance test were similar among groups, HFr rats required higher insulin levels to maintain control plasma glucose levels. Midce fed the HFat diet developed significant alterations in GTT and ITT after 8 w, showing higher fasting glucose and insulin levels than controls. Dietary EC improved parameters of insulin resistance in both models of MetS. In liver and adipose tissue, EC inhibited/mitigated MetS-triggered impairment of the insulin pathway. EC acted in part inhibiting events that underly MetS-induced insulin resistance: i- oxidative stress and increased NADPH oxidase expression, ii- activation of redox-sensitive signals (JNK, IKK/NF-kB), iii- inflammation, and iv- select subarms of the unfolded protein response. Results indicate that dietary EC supplementation may provide potential benefits against insulin resistance and MetS.