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Defective NOD2 peptidoglycan sensing promotes diet-induced inflammation, dysbiosis, and insulin resistance

Pattern recognition receptors link metabolite and bacteria-derived inflammation to insulin resistance during obesity. We demonstrate that NOD2 detection of bacterial cell wall peptidoglycan (PGN) regulates metabolic inflammation and insulin sensitivity. An obesity-promoting high-fat diet (HFD) incre...

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Autores principales: Denou, Emmanuel, Lolmède, Karine, Garidou, Lucile, Pomie, Celine, Chabo, Chantal, Lau, Trevor C, Fullerton, Morgan D, Nigro, Giulia, Zakaroff-Girard, Alexia, Luche, Elodie, Garret, Céline, Serino, Matteo, Amar, Jacques, Courtney, Michael, Cavallari, Joseph F, Henriksbo, Brandyn D, Barra, Nicole G, Foley, Kevin P, McPhee, Joseph B, Duggan, Brittany M, O'Neill, Hayley M, Lee, Amanda J, Sansonetti, Philippe, Ashkar, Ali A, Khan, Waliul I, Surette, Michael G, Bouloumié, Anne, Steinberg, Gregory R, Burcelin, Rémy, Schertzer, Jonathan D
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BlackWell Publishing Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4364944/
https://www.ncbi.nlm.nih.gov/pubmed/25666722
http://dx.doi.org/10.15252/emmm.201404169
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author Denou, Emmanuel
Lolmède, Karine
Garidou, Lucile
Pomie, Celine
Chabo, Chantal
Lau, Trevor C
Fullerton, Morgan D
Nigro, Giulia
Zakaroff-Girard, Alexia
Luche, Elodie
Garret, Céline
Serino, Matteo
Amar, Jacques
Courtney, Michael
Cavallari, Joseph F
Henriksbo, Brandyn D
Barra, Nicole G
Foley, Kevin P
McPhee, Joseph B
Duggan, Brittany M
O'Neill, Hayley M
Lee, Amanda J
Sansonetti, Philippe
Ashkar, Ali A
Khan, Waliul I
Surette, Michael G
Bouloumié, Anne
Steinberg, Gregory R
Burcelin, Rémy
Schertzer, Jonathan D
author_facet Denou, Emmanuel
Lolmède, Karine
Garidou, Lucile
Pomie, Celine
Chabo, Chantal
Lau, Trevor C
Fullerton, Morgan D
Nigro, Giulia
Zakaroff-Girard, Alexia
Luche, Elodie
Garret, Céline
Serino, Matteo
Amar, Jacques
Courtney, Michael
Cavallari, Joseph F
Henriksbo, Brandyn D
Barra, Nicole G
Foley, Kevin P
McPhee, Joseph B
Duggan, Brittany M
O'Neill, Hayley M
Lee, Amanda J
Sansonetti, Philippe
Ashkar, Ali A
Khan, Waliul I
Surette, Michael G
Bouloumié, Anne
Steinberg, Gregory R
Burcelin, Rémy
Schertzer, Jonathan D
author_sort Denou, Emmanuel
collection PubMed
description Pattern recognition receptors link metabolite and bacteria-derived inflammation to insulin resistance during obesity. We demonstrate that NOD2 detection of bacterial cell wall peptidoglycan (PGN) regulates metabolic inflammation and insulin sensitivity. An obesity-promoting high-fat diet (HFD) increased NOD2 in hepatocytes and adipocytes, and NOD2(−/−) mice have increased adipose tissue and liver inflammation and exacerbated insulin resistance during a HFD. This effect is independent of altered adiposity or NOD2 in hematopoietic-derived immune cells. Instead, increased metabolic inflammation and insulin resistance in NOD2(−/−) mice is associated with increased commensal bacterial translocation from the gut into adipose tissue and liver. An intact PGN-NOD2 sensing system regulated gut mucosal bacterial colonization and a metabolic tissue dysbiosis that is a potential trigger for increased metabolic inflammation and insulin resistance. Gut dysbiosis in HFD-fed NOD2(−/−) mice is an independent and transmissible factor that contributes to metabolic inflammation and insulin resistance when transferred to WT, germ-free mice. These findings warrant scrutiny of bacterial component detection, dysbiosis, and protective immune responses in the links between inflammatory gut and metabolic diseases, including diabetes.
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spelling pubmed-43649442015-03-23 Defective NOD2 peptidoglycan sensing promotes diet-induced inflammation, dysbiosis, and insulin resistance Denou, Emmanuel Lolmède, Karine Garidou, Lucile Pomie, Celine Chabo, Chantal Lau, Trevor C Fullerton, Morgan D Nigro, Giulia Zakaroff-Girard, Alexia Luche, Elodie Garret, Céline Serino, Matteo Amar, Jacques Courtney, Michael Cavallari, Joseph F Henriksbo, Brandyn D Barra, Nicole G Foley, Kevin P McPhee, Joseph B Duggan, Brittany M O'Neill, Hayley M Lee, Amanda J Sansonetti, Philippe Ashkar, Ali A Khan, Waliul I Surette, Michael G Bouloumié, Anne Steinberg, Gregory R Burcelin, Rémy Schertzer, Jonathan D EMBO Mol Med Research Articles Pattern recognition receptors link metabolite and bacteria-derived inflammation to insulin resistance during obesity. We demonstrate that NOD2 detection of bacterial cell wall peptidoglycan (PGN) regulates metabolic inflammation and insulin sensitivity. An obesity-promoting high-fat diet (HFD) increased NOD2 in hepatocytes and adipocytes, and NOD2(−/−) mice have increased adipose tissue and liver inflammation and exacerbated insulin resistance during a HFD. This effect is independent of altered adiposity or NOD2 in hematopoietic-derived immune cells. Instead, increased metabolic inflammation and insulin resistance in NOD2(−/−) mice is associated with increased commensal bacterial translocation from the gut into adipose tissue and liver. An intact PGN-NOD2 sensing system regulated gut mucosal bacterial colonization and a metabolic tissue dysbiosis that is a potential trigger for increased metabolic inflammation and insulin resistance. Gut dysbiosis in HFD-fed NOD2(−/−) mice is an independent and transmissible factor that contributes to metabolic inflammation and insulin resistance when transferred to WT, germ-free mice. These findings warrant scrutiny of bacterial component detection, dysbiosis, and protective immune responses in the links between inflammatory gut and metabolic diseases, including diabetes. BlackWell Publishing Ltd 2015-03 2015-02-09 /pmc/articles/PMC4364944/ /pubmed/25666722 http://dx.doi.org/10.15252/emmm.201404169 Text en © 2015 The Authors. Published under the terms of the CC BY 4.0 license http://creativecommons.org/licenses/by/4.0/ This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Denou, Emmanuel
Lolmède, Karine
Garidou, Lucile
Pomie, Celine
Chabo, Chantal
Lau, Trevor C
Fullerton, Morgan D
Nigro, Giulia
Zakaroff-Girard, Alexia
Luche, Elodie
Garret, Céline
Serino, Matteo
Amar, Jacques
Courtney, Michael
Cavallari, Joseph F
Henriksbo, Brandyn D
Barra, Nicole G
Foley, Kevin P
McPhee, Joseph B
Duggan, Brittany M
O'Neill, Hayley M
Lee, Amanda J
Sansonetti, Philippe
Ashkar, Ali A
Khan, Waliul I
Surette, Michael G
Bouloumié, Anne
Steinberg, Gregory R
Burcelin, Rémy
Schertzer, Jonathan D
Defective NOD2 peptidoglycan sensing promotes diet-induced inflammation, dysbiosis, and insulin resistance
title Defective NOD2 peptidoglycan sensing promotes diet-induced inflammation, dysbiosis, and insulin resistance
title_full Defective NOD2 peptidoglycan sensing promotes diet-induced inflammation, dysbiosis, and insulin resistance
title_fullStr Defective NOD2 peptidoglycan sensing promotes diet-induced inflammation, dysbiosis, and insulin resistance
title_full_unstemmed Defective NOD2 peptidoglycan sensing promotes diet-induced inflammation, dysbiosis, and insulin resistance
title_short Defective NOD2 peptidoglycan sensing promotes diet-induced inflammation, dysbiosis, and insulin resistance
title_sort defective nod2 peptidoglycan sensing promotes diet-induced inflammation, dysbiosis, and insulin resistance
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4364944/
https://www.ncbi.nlm.nih.gov/pubmed/25666722
http://dx.doi.org/10.15252/emmm.201404169
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