Intestinal protection by proanthocyanidins involves anti-oxidative and anti-inflammatory actions in association with an improvement of insulin sensitivity, lipid and glucose homeostasis

Abstract Recent advances have added another dimension to the complexity of cardiometabolic disorders (CMD) by directly implicating the gastrointestinal tract as a key player. In fact, multiple factors could interfere with intestinal homeostasis and elicit extra-intestinal CMD. As oxidative stress (O...

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Autores principales:	Mireille Koudoufio, Francis Feldman, Lena Ahmarani, Edgard Delvin, Schohraya Spahis, Yves Desjardins, Emile Levy
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9b3f93f7fc3143148477bbad6ab910a1
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spelling	oai:doaj.org-article:9b3f93f7fc3143148477bbad6ab910a12021-12-02T14:21:58ZIntestinal protection by proanthocyanidins involves anti-oxidative and anti-inflammatory actions in association with an improvement of insulin sensitivity, lipid and glucose homeostasis10.1038/s41598-020-80587-52045-2322https://doaj.org/article/9b3f93f7fc3143148477bbad6ab910a12021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80587-5https://doaj.org/toc/2045-2322Abstract Recent advances have added another dimension to the complexity of cardiometabolic disorders (CMD) by directly implicating the gastrointestinal tract as a key player. In fact, multiple factors could interfere with intestinal homeostasis and elicit extra-intestinal CMD. As oxidative stress (OxS), inflammation, insulin resistance and lipid abnormalities are among the most disruptive events, the aim of the present study is to explore whether proanthocyanidins (PACs) exert protective effects against these disorders. To this end, fully differentiated intestinal Caco-2/15 cells were pre-incubated with PACs with and without the pro-oxidant and pro-inflammatory iron/ascorbate (Fe/Asc). PACs significantly reduce malondialdehyde, a biomarker of lipid peroxidation, and raise antioxidant SOD2 and GPx via the increase of NRF2/Keap1 ratio. Likewise, PACs decrease the inflammatory agents TNFα and COX2 through abrogation of NF-κB. Moreover, according to crucial biomarkers, PACs result in lipid homeostasis improvement as reflected by enhanced fatty acid β-oxidation, diminished lipogenesis, and lowered gluconeogenesis as a result of PPARα, γ and SREBP1c modulation. Since these metabolic routes are mainly regulated by insulin sensitivity, we have examined the insulin signaling pathway and found an upregulation of phosphoPI3K/Akt and downregulation of p38-MAPK expressions, indicating beneficial effects in response to PACs. Taken together, PACs display the potential to counterbalance OxS and inflammation in Fe/Asc-exposed intestinal cells, in association with an improvement of insulin sensitivity, which ameliorates lipid and glucose homeostasis.Mireille KoudoufioFrancis FeldmanLena AhmaraniEdgard DelvinSchohraya SpahisYves DesjardinsEmile LevyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mireille Koudoufio Francis Feldman Lena Ahmarani Edgard Delvin Schohraya Spahis Yves Desjardins Emile Levy Intestinal protection by proanthocyanidins involves anti-oxidative and anti-inflammatory actions in association with an improvement of insulin sensitivity, lipid and glucose homeostasis
description	Abstract Recent advances have added another dimension to the complexity of cardiometabolic disorders (CMD) by directly implicating the gastrointestinal tract as a key player. In fact, multiple factors could interfere with intestinal homeostasis and elicit extra-intestinal CMD. As oxidative stress (OxS), inflammation, insulin resistance and lipid abnormalities are among the most disruptive events, the aim of the present study is to explore whether proanthocyanidins (PACs) exert protective effects against these disorders. To this end, fully differentiated intestinal Caco-2/15 cells were pre-incubated with PACs with and without the pro-oxidant and pro-inflammatory iron/ascorbate (Fe/Asc). PACs significantly reduce malondialdehyde, a biomarker of lipid peroxidation, and raise antioxidant SOD2 and GPx via the increase of NRF2/Keap1 ratio. Likewise, PACs decrease the inflammatory agents TNFα and COX2 through abrogation of NF-κB. Moreover, according to crucial biomarkers, PACs result in lipid homeostasis improvement as reflected by enhanced fatty acid β-oxidation, diminished lipogenesis, and lowered gluconeogenesis as a result of PPARα, γ and SREBP1c modulation. Since these metabolic routes are mainly regulated by insulin sensitivity, we have examined the insulin signaling pathway and found an upregulation of phosphoPI3K/Akt and downregulation of p38-MAPK expressions, indicating beneficial effects in response to PACs. Taken together, PACs display the potential to counterbalance OxS and inflammation in Fe/Asc-exposed intestinal cells, in association with an improvement of insulin sensitivity, which ameliorates lipid and glucose homeostasis.
format	article
author	Mireille Koudoufio Francis Feldman Lena Ahmarani Edgard Delvin Schohraya Spahis Yves Desjardins Emile Levy
author_facet	Mireille Koudoufio Francis Feldman Lena Ahmarani Edgard Delvin Schohraya Spahis Yves Desjardins Emile Levy
author_sort	Mireille Koudoufio
title	Intestinal protection by proanthocyanidins involves anti-oxidative and anti-inflammatory actions in association with an improvement of insulin sensitivity, lipid and glucose homeostasis
title_short	Intestinal protection by proanthocyanidins involves anti-oxidative and anti-inflammatory actions in association with an improvement of insulin sensitivity, lipid and glucose homeostasis
title_full	Intestinal protection by proanthocyanidins involves anti-oxidative and anti-inflammatory actions in association with an improvement of insulin sensitivity, lipid and glucose homeostasis
title_fullStr	Intestinal protection by proanthocyanidins involves anti-oxidative and anti-inflammatory actions in association with an improvement of insulin sensitivity, lipid and glucose homeostasis
title_full_unstemmed	Intestinal protection by proanthocyanidins involves anti-oxidative and anti-inflammatory actions in association with an improvement of insulin sensitivity, lipid and glucose homeostasis
title_sort	intestinal protection by proanthocyanidins involves anti-oxidative and anti-inflammatory actions in association with an improvement of insulin sensitivity, lipid and glucose homeostasis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9b3f93f7fc3143148477bbad6ab910a1
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Intestinal protection by proanthocyanidins involves anti-oxidative and anti-inflammatory actions in association with an improvement of insulin sensitivity, lipid and glucose homeostasis

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