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Free Radic Biol Med. 2014 Jul;72:247-56. doi: 10.1016/j.freeradbiomed.2014.04.011. Epub 2014 Apr 16.

(-)-Epicatechin mitigates high-fructose-associated insulin resistance by modulating redox signaling and endoplasmic reticulum stress.

Author information

1
Department of Nutrition, University of California at Davis, Davis, CA 95616, USA.
2
Department of Pathology, School of Medicine, National University of Cuyo and Institute of Medicine and Experimental Biology-CONICET, Mendoza, Argentina.
3
Department of Nutrition, University of California at Davis, Davis, CA 95616, USA; Department of Internal Medicine, University of California at Davis, Davis, CA 95616, USA.
4
Department of Nutrition, University of California at Davis, Davis, CA 95616, USA; Physical Chemistry-IBIMOL, School of Pharmacy and Biochemistry, University of Buenos Aires-CONICET, Buenos Aires, Argentina.
5
Department of Nutrition, University of California at Davis, Davis, CA 95616, USA; Department of Environmental Toxicology, University of California at Davis, Davis, CA 95616, USA. Electronic address: poteiza@ucdavis.edu.

Abstract

We investigated the capacity of dietary (-)-epicatechin (EC) to mitigate insulin resistance through the modulation of redox-regulated mechanisms in a rat model of metabolic syndrome. Adolescent rats were fed a regular chow diet without or with high fructose (HFr; 10% w/v) in drinking water for 8 weeks, and a group of HFr-fed rats was supplemented with EC in the diet. HFr-fed rats developed insulin resistance, which was mitigated by EC supplementation. Accordingly, the activation of components of the insulin signaling cascade (insulin receptor, IRS1, Akt, and ERK1/2) was impaired, whereas negative regulators (PKC, IKK, JNK, and PTP1B) were upregulated in the liver and adipose tissue of HFr rats. These alterations were partially or totally prevented by EC supplementation. In addition, EC inhibited events that contribute to insulin resistance: HFr-associated increased expression and activity of NADPH oxidase, activation of redox-sensitive signals, expression of NF-κB-regulated proinflammatory cytokines and chemokines, and some sub-arms of endoplasmic reticulum stress signaling. Collectively, these findings indicate that EC supplementation can mitigate HFr-induced insulin resistance and are relevant for defining interventions that can prevent/mitigate MetS-associated insulin resistance.

KEYWORDS:

Endoplasmic reticulum stress; Epicatechin and flavonoids; Free radicals; Insulin resistance; Metabolic syndrome; NADPH oxidase; Redox signaling

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