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

Autores
Cremonini, Eleonora; Wang, Ziwei; Bettaieb, Ahmed; Adamo, Ana María; Daveri, Elena; Mills, David A.; Kalanetra, Karen M.; Haj, Fawaz G.; Karakas, Sidika; Oteiza, Patricia I.
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
Fil: Cremonini, Eleonora. University of California; Estados Unidos
Fil: Wang, Ziwei. University of California; Estados Unidos
Fil: Bettaieb, Ahmed. University of Tennessee; Estados Unidos
Fil: Adamo, Ana María. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Daveri, Elena. University of California; Estados Unidos
Fil: Mills, David A.. University of California; Estados Unidos
Fil: Kalanetra, Karen M.. University of California; Estados Unidos
Fil: Haj, Fawaz G.. University of California; Estados Unidos
Fil: Karakas, Sidika. University of California; Estados Unidos
Fil: Oteiza, Patricia I.. University of California; Estados Unidos
Materia
(-)-EPICATECHIN
ENDOTOXEMIA
INSULIN RESISTANCE
INTESTINAL PERMEABILITY
NADPH OXIDASE
STEATOSIS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/93073
Acceder
id CONICETDig_7d4a4f0c6f59ba0953e6f91264949587
oai_identifier_str oai:ri.conicet.gov.ar:11336/93073
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling (-)-Epicatechin protects the intestinal barrier from high fat diet-induced permeabilization: Implications for steatosis and insulin resistanceCremonini, EleonoraWang, ZiweiBettaieb, AhmedAdamo, Ana MaríaDaveri, ElenaMills, David A.Kalanetra, Karen M.Haj, Fawaz G.Karakas, SidikaOteiza, Patricia I.(-)-EPICATECHINENDOTOXEMIAINSULIN RESISTANCEINTESTINAL PERMEABILITYNADPH OXIDASESTEATOSIShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Increased 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.Fil: Cremonini, Eleonora. University of California; Estados UnidosFil: Wang, Ziwei. University of California; Estados UnidosFil: Bettaieb, Ahmed. University of Tennessee; Estados UnidosFil: Adamo, Ana María. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Daveri, Elena. University of California; Estados UnidosFil: Mills, David A.. University of California; Estados UnidosFil: Kalanetra, Karen M.. University of California; Estados UnidosFil: Haj, Fawaz G.. University of California; Estados UnidosFil: Karakas, Sidika. University of California; Estados UnidosFil: Oteiza, Patricia I.. University of California; Estados UnidosElsevier2018-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/93073Cremonini, Eleonora; Wang, Ziwei; Bettaieb, Ahmed; Adamo, Ana María; Daveri, Elena; et al.; (-)-Epicatechin protects the intestinal barrier from high fat diet-induced permeabilization: Implications for steatosis and insulin resistance; Elsevier; Redox Biology; 14; 4-2018; 588-5992213-2317CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.redox.2017.11.002info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S2213231717307668info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:46:49Zoai:ri.conicet.gov.ar:11336/93073instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:46:50.281CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv (-)-Epicatechin protects the intestinal barrier from high fat diet-induced permeabilization: Implications for steatosis and insulin resistance
title (-)-Epicatechin protects the intestinal barrier from high fat diet-induced permeabilization: Implications for steatosis and insulin resistance
spellingShingle (-)-Epicatechin protects the intestinal barrier from high fat diet-induced permeabilization: Implications for steatosis and insulin resistance
Cremonini, Eleonora
(-)-EPICATECHIN
ENDOTOXEMIA
INSULIN RESISTANCE
INTESTINAL PERMEABILITY
NADPH OXIDASE
STEATOSIS
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
dc.creator.none.fl_str_mv Cremonini, Eleonora
Wang, Ziwei
Bettaieb, Ahmed
Adamo, Ana María
Daveri, Elena
Mills, David A.
Kalanetra, Karen M.
Haj, Fawaz G.
Karakas, Sidika
Oteiza, Patricia I.
author Cremonini, Eleonora
author_facet Cremonini, Eleonora
Wang, Ziwei
Bettaieb, Ahmed
Adamo, Ana María
Daveri, Elena
Mills, David A.
Kalanetra, Karen M.
Haj, Fawaz G.
Karakas, Sidika
Oteiza, Patricia I.
author_role author
author2 Wang, Ziwei
Bettaieb, Ahmed
Adamo, Ana María
Daveri, Elena
Mills, David A.
Kalanetra, Karen M.
Haj, Fawaz G.
Karakas, Sidika
Oteiza, Patricia I.
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv (-)-EPICATECHIN
ENDOTOXEMIA
INSULIN RESISTANCE
INTESTINAL PERMEABILITY
NADPH OXIDASE
STEATOSIS
topic (-)-EPICATECHIN
ENDOTOXEMIA
INSULIN RESISTANCE
INTESTINAL PERMEABILITY
NADPH OXIDASE
STEATOSIS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv 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.
Fil: Cremonini, Eleonora. University of California; Estados Unidos
Fil: Wang, Ziwei. University of California; Estados Unidos
Fil: Bettaieb, Ahmed. University of Tennessee; Estados Unidos
Fil: Adamo, Ana María. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Daveri, Elena. University of California; Estados Unidos
Fil: Mills, David A.. University of California; Estados Unidos
Fil: Kalanetra, Karen M.. University of California; Estados Unidos
Fil: Haj, Fawaz G.. University of California; Estados Unidos
Fil: Karakas, Sidika. University of California; Estados Unidos
Fil: Oteiza, Patricia I.. University of California; Estados Unidos
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 (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.
publishDate 2018
dc.date.none.fl_str_mv 2018-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/93073
Cremonini, Eleonora; Wang, Ziwei; Bettaieb, Ahmed; Adamo, Ana María; Daveri, Elena; et al.; (-)-Epicatechin protects the intestinal barrier from high fat diet-induced permeabilization: Implications for steatosis and insulin resistance; Elsevier; Redox Biology; 14; 4-2018; 588-599
2213-2317
CONICET Digital
CONICET
url http://hdl.handle.net/11336/93073
identifier_str_mv Cremonini, Eleonora; Wang, Ziwei; Bettaieb, Ahmed; Adamo, Ana María; Daveri, Elena; et al.; (-)-Epicatechin protects the intestinal barrier from high fat diet-induced permeabilization: Implications for steatosis and insulin resistance; Elsevier; Redox Biology; 14; 4-2018; 588-599
2213-2317
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.redox.2017.11.002
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S2213231717307668
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1842268819023724544
score 13.13397

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