Format

Send to:

Choose Destination
See comment in PubMed Commons below
EMBO Mol Med. 2015 Feb 9;7(3):259-74. doi: 10.15252/emmm.201404169.

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

Author information

  • 1Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada.
  • 2Institut National de la Santé et de la Recherche Médicale (INSERM), Toulouse, France Université Paul Sabatier (UPS) Unité Mixte de Recherche (UMR) 1048 Institut des Maladies Métaboliques et Cardiovasculaires (I2MC) Team 1: «stroma-vascular cells of adipose tissue», Toulouse, France.
  • 3Institut National de la Santé et de la Recherche Médicale (INSERM), Toulouse, France Université Paul Sabatier (UPS) Unité Mixte de Recherche (UMR) 1048 Institut des Maladies Métaboliques et Cardiovasculaires (I2MC) Team 2: «Intestinal Risk Factors, Diabetes, Dyslipidemia», Toulouse Cedex 4, France.
  • 4Institut National de la Santé et de la Recherche Médicale (INSERM), Toulouse, France Université Paul Sabatier (UPS) Unité Mixte de Recherche (UMR) 1048 Institut des Maladies Métaboliques et Cardiovasculaires (I2MC) Team 2: «Intestinal Risk Factors, Diabetes, Dyslipidemia», Toulouse Cedex 4, France VAIOMER SAS, Prologue Biotech, Labège, France.
  • 5Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada Department of Medicine, McMaster University, Hamilton, ON, Canada.
  • 6Unité de Pathogénie Microbienne Moléculaire and Unité INSERM 786 Institut Pasteur, Paris, France.
  • 7VAIOMER SAS, Prologue Biotech, Labège, France.
  • 8Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
  • 9Department of Medicine, McMaster University, Hamilton, ON, Canada.
  • 10Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada Farncombe Family Digestive Health Research Institute McMaster University, Hamilton, ON, Canada.
  • 11Department of Medicine, McMaster University, Hamilton, ON, Canada Farncombe Family Digestive Health Research Institute McMaster University, Hamilton, ON, Canada.
  • 12Institut National de la Santé et de la Recherche Médicale (INSERM), Toulouse, France Université Paul Sabatier (UPS) Unité Mixte de Recherche (UMR) 1048 Institut des Maladies Métaboliques et Cardiovasculaires (I2MC) Team 2: «Intestinal Risk Factors, Diabetes, Dyslipidemia», Toulouse Cedex 4, France remy.burcelin@inserm.fr schertze@mcmaster.ca.
  • 13Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada remy.burcelin@inserm.fr schertze@mcmaster.ca.

Abstract

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.

© 2015 The Authors. Published under the terms of the CC BY 4.0 license.

KEYWORDS:

diabetes; glucose; metabolic inflammation; microbiome; obesity

PMID:
25666722
[PubMed - indexed for MEDLINE]
PMCID:
PMC4364944
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk