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Redox Biol. 2018 Apr;14:588-599. doi: 10.1016/j.redox.2017.11.002. Epub 2017 Nov 7.

(-)-Epicatechin protects the intestinal barrier from high fat diet-induced permeabilization: Implications for steatosis and insulin resistance.

Author information

1
Department of Nutrition, University of California, Davis, USA; Department of Environmental Toxicology, University of California, Davis, USA.
2
Department of Nutrition, University of Tennessee-Knoxville, Knoxville, TN, USA.
3
Department of Biological Chemistry and IQUIFIB (UBA-CONICET), School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.
4
Department of Food Science and Technology, University of California, Davis, USA; Department of Viticulture and Enology, University of California, Davis, USA.
5
Department of Internal Medicine, University of California, Davis, USA.
6
Department of Nutrition, University of California, Davis, USA; Department of Environmental Toxicology, University of California, Davis, USA. Electronic address: poteiza@ucdavis.edu.

Abstract

Increased permeability of the intestinal barrier is proposed as an underlying factor for obesity-associated pathologies. Consumption of high fat diets (HFD) is associated with increased intestinal permeabilization and increased paracellular transport of endotoxins which can promote steatosis and insulin resistance. This study investigated whether dietary (-)-epicatechin (EC) supplementation can protect the intestinal barrier against HFD-induced permeabilization and endotoxemia, and mitigate liver damage and insulin resistance. Mechanisms leading to loss of integrity and function of the tight junction (TJ) were characterized. Consumption of a HFD for 15 weeks caused obesity, steatosis, and insulin resistance in male C57BL/6J mice. This was associated with increased intestinal permeability, decreased expression of ileal TJ proteins, and endotoxemia. Supplementation with EC (2-20mg/kg body weight) mitigated all these adverse effects. EC acted modulating cell signals and the gut hormone GLP-2, which are central to the regulation of intestinal permeability. Thus, EC prevented HFD-induced ileum NOX1/NOX4 upregulation, protein oxidation, and the activation of the redox-sensitive NF-κB and ERK1/2 pathways. Supporting NADPH oxidase as a target of EC actions, in Caco-2 cells EC and apocynin inhibited tumor necrosis alpha (TNFα)-induced NOX1/NOX4 overexpression, protein oxidation and monolayer permeabilization. Together, our findings demonstrate protective effects of EC against HFD-induced increased intestinal permeability and endotoxemia. This can in part underlie EC capacity to prevent steatosis and insulin resistance occurring as a consequence of HFD consumption.

KEYWORDS:

(-)-Epicatechin; Endotoxemia; Insulin resistance; Intestinal permeability; NADPH oxidase; Steatosis

PMID:
29154190
PMCID:
PMC5691220
DOI:
10.1016/j.redox.2017.11.002
[Indexed for MEDLINE]
Free PMC Article

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