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

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

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 ins...

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Main Authors: Eleonora Cremonini, Ziwei Wang, Ahmed Bettaieb, Ana M. Adamo, Elena Daveri, David A. Mills, Karen M. Kalanetra, Fawaz G. Haj, Sidika Karakas, Patricia I. Oteiza
Format: Article
Language:English
Published: Elsevier 2018-04-01
Series:Redox Biology
Online Access:http://www.sciencedirect.com/science/article/pii/S2213231717307668
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spelling doaj-418ffe56f0b346b8a2e09ad1d50eb8982020-11-25T02:36:01ZengElsevierRedox Biology2213-23172018-04-0114588599(-)-Epicatechin protects the intestinal barrier from high fat diet-induced permeabilization: Implications for steatosis and insulin resistanceEleonora Cremonini0Ziwei Wang1Ahmed Bettaieb2Ana M. Adamo3Elena Daveri4David A. Mills5Karen M. Kalanetra6Fawaz G. Haj7Sidika Karakas8Patricia I. Oteiza9Department of Nutrition, University of California, Davis, USA; Department of Environmental Toxicology, University of California, Davis, USADepartment of Nutrition, University of California, Davis, USA; Department of Environmental Toxicology, University of California, Davis, USADepartment of Nutrition, University of Tennessee-Knoxville, Knoxville, TN, USADepartment of Biological Chemistry and IQUIFIB (UBA-CONICET), School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, ArgentinaDepartment of Nutrition, University of California, Davis, USA; Department of Environmental Toxicology, University of California, Davis, USADepartment of Food Science and Technology, University of California, Davis, USA; Department of Viticulture and Enology, University of California, Davis, USADepartment of Food Science and Technology, University of California, Davis, USA; Department of Viticulture and Enology, University of California, Davis, USADepartment of Nutrition, University of California, Davis, USA; Department of Environmental Toxicology, University of California, Davis, USADepartment of Internal Medicine, University of California, Davis, USADepartment of Nutrition, University of California, Davis, USA; Department of Environmental Toxicology, University of California, Davis, USA; Correspondence to: Departments of Nutrition/Environmental Toxicology, University of California, Davis, One Shields Avenue, Davis, CA 95616, USA.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 (2â20 mg/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: Intestinal permeability, (-)-Epicatechin, Steatosis, Insulin resistance, Endotoxemia, NADPH oxidasehttp://www.sciencedirect.com/science/article/pii/S2213231717307668
collection DOAJ
language English
format Article
sources DOAJ
author Eleonora Cremonini
Ziwei Wang
Ahmed Bettaieb
Ana M. Adamo
Elena Daveri
David A. Mills
Karen M. Kalanetra
Fawaz G. Haj
Sidika Karakas
Patricia I. Oteiza
spellingShingle Eleonora Cremonini
Ziwei Wang
Ahmed Bettaieb
Ana M. Adamo
Elena Daveri
David A. Mills
Karen M. Kalanetra
Fawaz G. Haj
Sidika Karakas
Patricia I. Oteiza
(-)-Epicatechin protects the intestinal barrier from high fat diet-induced permeabilization: Implications for steatosis and insulin resistance
Redox Biology
author_facet Eleonora Cremonini
Ziwei Wang
Ahmed Bettaieb
Ana M. Adamo
Elena Daveri
David A. Mills
Karen M. Kalanetra
Fawaz G. Haj
Sidika Karakas
Patricia I. Oteiza
author_sort Eleonora Cremonini
title (-)-Epicatechin protects the intestinal barrier from high fat diet-induced permeabilization: Implications for steatosis and insulin resistance
title_short (-)-Epicatechin protects the intestinal barrier from high fat diet-induced permeabilization: Implications for steatosis and insulin resistance
title_full (-)-Epicatechin protects the intestinal barrier from high fat diet-induced permeabilization: Implications for steatosis and insulin resistance
title_fullStr (-)-Epicatechin protects the intestinal barrier from high fat diet-induced permeabilization: Implications for steatosis and insulin resistance
title_full_unstemmed (-)-Epicatechin protects the intestinal barrier from high fat diet-induced permeabilization: Implications for steatosis and insulin resistance
title_sort (-)-epicatechin protects the intestinal barrier from high fat diet-induced permeabilization: implications for steatosis and insulin resistance
publisher Elsevier
series Redox Biology
issn 2213-2317
publishDate 2018-04-01
description 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 (2â20 mg/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: Intestinal permeability, (-)-Epicatechin, Steatosis, Insulin resistance, Endotoxemia, NADPH oxidase
url http://www.sciencedirect.com/science/article/pii/S2213231717307668
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