TY - JOUR
T1 - Defective NOD2 peptidoglycan sensing promotes diet-induced inflammation, dysbiosis, and insulin resistance
AU - Denou, Emmanuel
AU - Lolmède, Karine
AU - Garidou, Lucile
AU - Pomie, Celine
AU - Chabo, Chantal
AU - Lau, Trevor C
AU - Fullerton, Morgan D
AU - Nigro, Giulia
AU - Zakaroff-Girard, Alexia
AU - Luche, Elodie
AU - Garret, Céline
AU - Serino, Matteo
AU - Amar, Jacques
AU - Courtney, Michael
AU - Cavallari, Joseph F
AU - Henriksbo, Brandyn D
AU - Barra, Nicole G
AU - Foley, Kevin P
AU - McPhee, Joseph B
AU - Duggan, Brittany M
AU - O'Neill, Hayley M
AU - Lee, Amanda J
AU - Sansonetti, Philippe
AU - Ashkar, Ali A
AU - Khan, Waliul I
AU - Surette, Michael G
AU - Bouloumié, Anne
AU - Steinberg, Gregory R
AU - Burcelin, Rémy
AU - Schertzer, Jonathan D
N1 - © 2015 The Authors. Published under the terms of the CC BY 4.0 license.
PY - 2015/2/9
Y1 - 2015/2/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84929843622&partnerID=8YFLogxK
U2 - 10.15252/emmm.201404169
DO - 10.15252/emmm.201404169
M3 - Article
C2 - 25666722
SN - 1757-4676
VL - 7
SP - 259
EP - 274
JO - EMBO Molecular Medicine
JF - EMBO Molecular Medicine
IS - 3
ER -
