Defective <scp>NOD</scp>2 peptidoglycan sensing promotes diet‐induced inflammation, dysbiosis, and insulin resistance
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- Emmanuel Denou
- Department of Biochemistry and Biomedical Sciences McMaster University Hamilton ON Canada
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- Karine Lolmède
- Institut National de la Santé et de la Recherche Médicale (INSERM) Toulouse France
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- Lucile Garidou
- Institut National de la Santé et de la Recherche Médicale (INSERM) Toulouse France
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- Celine Pomie
- Institut National de la Santé et de la Recherche Médicale (INSERM) Toulouse France
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- Chantal Chabo
- Institut National de la Santé et de la Recherche Médicale (INSERM) Toulouse France
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- Trevor C Lau
- Department of Biochemistry and Biomedical Sciences McMaster University Hamilton ON Canada
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- Morgan D Fullerton
- Department of Biochemistry and Biomedical Sciences McMaster University Hamilton ON Canada
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- Giulia Nigro
- Unité de Pathogénie Microbienne Moléculaire and Unité INSERM 786 Institut Pasteur Paris France
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- Alexia Zakaroff‐Girard
- Institut National de la Santé et de la Recherche Médicale (INSERM) Toulouse France
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- Elodie Luche
- Institut National de la Santé et de la Recherche Médicale (INSERM) Toulouse France
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- Céline Garret
- Institut National de la Santé et de la Recherche Médicale (INSERM) Toulouse France
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- Matteo Serino
- Institut National de la Santé et de la Recherche Médicale (INSERM) Toulouse France
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- Jacques Amar
- Institut National de la Santé et de la Recherche Médicale (INSERM) Toulouse France
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- Michael Courtney
- VAIOMER SAS Prologue Biotech Labège France
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- Joseph F Cavallari
- Department of Biochemistry and Biomedical Sciences McMaster University Hamilton ON Canada
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- Brandyn D Henriksbo
- Department of Biochemistry and Biomedical Sciences McMaster University Hamilton ON Canada
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- Nicole G Barra
- Department of Pathology and Molecular Medicine McMaster University Hamilton ON Canada
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- Kevin P Foley
- Department of Biochemistry and Biomedical Sciences McMaster University Hamilton ON Canada
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- Joseph B McPhee
- Department of Biochemistry and Biomedical Sciences McMaster University Hamilton ON Canada
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- Brittany M Duggan
- Department of Biochemistry and Biomedical Sciences McMaster University Hamilton ON Canada
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- Hayley M O'Neill
- Department of Medicine McMaster University Hamilton ON Canada
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- Amanda J Lee
- Department of Pathology and Molecular Medicine McMaster University Hamilton ON Canada
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- Philippe Sansonetti
- Unité de Pathogénie Microbienne Moléculaire and Unité INSERM 786 Institut Pasteur Paris France
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- Ali A Ashkar
- Department of Pathology and Molecular Medicine McMaster University Hamilton ON Canada
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- Waliul I Khan
- Department of Pathology and Molecular Medicine McMaster University Hamilton ON Canada
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- Michael G Surette
- Department of Medicine McMaster University Hamilton ON Canada
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- Anne Bouloumié
- Institut National de la Santé et de la Recherche Médicale (INSERM) Toulouse France
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- Gregory R Steinberg
- Department of Medicine McMaster University Hamilton ON Canada
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- Rémy Burcelin
- Institut National de la Santé et de la Recherche Médicale (INSERM) Toulouse France
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- Jonathan D Schertzer
- Department of Biochemistry and Biomedical Sciences McMaster University Hamilton ON Canada
説明
<jats:title>Abstract</jats:title><jats:p>Pattern recognition receptors link metabolite and bacteria‐derived inflammation to insulin resistance during obesity. We demonstrate that <jats:styled-content style="fixed-case">NOD</jats:styled-content>2 detection of bacterial cell wall peptidoglycan (<jats:styled-content style="fixed-case">PGN</jats:styled-content>) regulates metabolic inflammation and insulin sensitivity. An obesity‐promoting high‐fat diet (<jats:styled-content style="fixed-case">HFD</jats:styled-content>) increased <jats:styled-content style="fixed-case">NOD</jats:styled-content>2 in hepatocytes and adipocytes, and <jats:styled-content style="fixed-case">NOD</jats:styled-content>2<jats:sup>−/−</jats:sup> mice have increased adipose tissue and liver inflammation and exacerbated insulin resistance during a <jats:styled-content style="fixed-case">HFD</jats:styled-content>. This effect is independent of altered adiposity or <jats:styled-content style="fixed-case">NOD</jats:styled-content>2 in hematopoietic‐derived immune cells. Instead, increased metabolic inflammation and insulin resistance in <jats:styled-content style="fixed-case">NOD</jats:styled-content>2<jats:sup>−/−</jats:sup> mice is associated with increased commensal bacterial translocation from the gut into adipose tissue and liver. An intact <jats:styled-content style="fixed-case">PGN</jats:styled-content>‐<jats:styled-content style="fixed-case">NOD</jats:styled-content>2 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 <jats:styled-content style="fixed-case">HFD</jats:styled-content>‐fed <jats:styled-content style="fixed-case">NOD</jats:styled-content>2<jats:sup>−/−</jats:sup> mice is an independent and transmissible factor that contributes to metabolic inflammation and insulin resistance when transferred to <jats:styled-content style="fixed-case">WT</jats:styled-content>, 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.</jats:p>
収録刊行物
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- EMBO Molecular Medicine
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EMBO Molecular Medicine 7 (3), 259-274, 2015-02-09
Springer Science and Business Media LLC