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

Eleonora Cremonini, Ziwei Wang, Ahmed Bettaieb, Ana M. Adamo, Elena Daveri, David A. Mills, Karen M. Kalanetra, Fawaz Haj, Siddika E Karakas, Patricia I. Oteiza

Research output: Contribution to journalArticle

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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 (2–20 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.

LanguageEnglish (US)
Pages588-599
Number of pages12
JournalRedox Biology
Volume14
DOIs
StatePublished - Apr 1 2018

Fingerprint

Catechin
High Fat Diet
Nutrition
Insulin Resistance
Fats
Insulin
Endotoxemia
Permeability
Obesity
Tight Junction Proteins
Oxidation
Caco-2 Cells
MAP Kinase Signaling System
Tight Junctions
NADPH Oxidase
Pathology
Dietary Supplements
Inbred C57BL Mouse
Ileum
Endotoxins

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry

Cite this

(-)-Epicatechin protects the intestinal barrier from high fat diet-induced permeabilization : Implications for steatosis and insulin resistance. / Cremonini, Eleonora; Wang, Ziwei; Bettaieb, Ahmed; Adamo, Ana M.; Daveri, Elena; Mills, David A.; Kalanetra, Karen M.; Haj, Fawaz; Karakas, Siddika E; Oteiza, Patricia I.

In: Redox Biology, Vol. 14, 01.04.2018, p. 588-599.

Research output: Contribution to journalArticle

Cremonini, Eleonora ; Wang, Ziwei ; Bettaieb, Ahmed ; Adamo, Ana M. ; Daveri, Elena ; Mills, David A. ; Kalanetra, Karen M. ; Haj, Fawaz ; Karakas, Siddika E ; Oteiza, Patricia I. / (-)-Epicatechin protects the intestinal barrier from high fat diet-induced permeabilization : Implications for steatosis and insulin resistance. In: Redox Biology. 2018 ; Vol. 14. pp. 588-599.
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AB - 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 (2–20 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.

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