Open AccessDefective NOD 2 peptidoglycan sensing promotes diet‐induced inflammation, dysbiosis, and insulin resistance
Author(s) -
Denou Emmanuel,
Lolmède Karine,
Garidou Lucile,
Pomie Celine,
Chabo Chantal,
Lau Trevor C,
Fullerton Morgan D,
Nigro Giulia,
ZakaroffGirard 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
Publication year - 2015
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201404169
Subject(s) - nod , insulin resistance , inflammation , dysbiosis , adipose tissue , nod mice , biology , medicine , endocrinology , immunology , gut flora , insulin , diabetes mellitus
Pattern recognition receptors link metabolite and bacteria‐derived inflammation to insulin resistance during obesity. We demonstrate that NOD 2 detection of bacterial cell wall peptidoglycan ( PGN ) regulates metabolic inflammation and insulin sensitivity. An obesity‐promoting high‐fat diet ( HFD ) increased NOD 2 in hepatocytes and adipocytes, and NOD 2 −/− mice have increased adipose tissue and liver inflammation and exacerbated insulin resistance during a HFD . This effect is independent of altered adiposity or NOD 2 in hematopoietic‐derived immune cells. Instead, increased metabolic inflammation and insulin resistance in NOD 2 −/− mice is associated with increased commensal bacterial translocation from the gut into adipose tissue and liver. An intact PGN ‐ NOD 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 HFD ‐fed NOD 2 −/− 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.