Defective NOD2 peptidoglycan sensing promotes diet‐induced inflammation, dysbiosis, and insulin resistance ATranscript levels of NOD2 in various tissues.

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Defective NOD2 peptidoglycan sensing promotes diet‐induced inflammation, dysbiosis, and insulin resistance ATranscript levels of NOD2 in various tissues of chow‐fed (n = 5, all tissues in both genotypes) and 16 week HFD‐fed (n = 6) WT and NOD2−/− mice, *P = 0.005, **P = 0.001, and ***P = 0.0004. BH&E histology and IHC of the macrophage marker F4/80 in adipose tissue from HFD‐fed WT and NOD2−/− mice (representative of n = 5 WT and n = 6 NOD2−/− mice). Scale bar equals 50 μm. C, DQuantification of immune cell and inflammatory markers (C) and pro‐inflammatory cytokines (D) in adipose tissue of chow‐fed (n = 5 in both genotypes) or HFD‐fed (n = 11 in both genotypes) WT and NOD2−/− mice, *P = 0.04, **P = 0.02, ##P = 0.004, and #P = 0.04. EQuantification of serum non‐esterified fatty acids (NEFA) in fasted and clamped HFD‐fed WT (n = 4) and NOD2−/− (n = 3) mice, *P = 0.0001. FQuantification of insulin‐stimulated pAktSer473 in gonadal adipose tissue at the end of the clamp in HFD‐fed WT (n = 5) and NOD2−/− mice (n = 5), *P = 0.04. GThe number of ampicillin‐resistant E. coli cfu per gram of visceral adipose tissue was determined in WT (n = 5) and NOD2−/− (n = 5) mice after oral administration of 109 cfu of WT or mutant (∆amiA) DsRed‐labeled E. coli, *P = 0.02. HQuantification of GFP‐positive E. coli in the adipose tissue stromal vascular fraction (SVF) from WT mice with no oral bacterial administration (CON, n = 3) or after administration of 109 cfu WT GFP‐positive E. coli (n = 4) or ∆amiA GFP‐positive E. coli (n = 4), *P = 0.03. Data information: In (A), *significantly different from chow‐fed WT mice. In (C–F), *significantly different from HFD‐fed WT mice. In (G), *significantly different from WT mice given WT E. coli. In (H), *significantly different from CON plus WT E. coli given to WT mice. #Significantly different from chow‐fed WT mice. An unpaired t‐test was used for comparisons between two conditions, whereas a 1‐way ANOVA was used for comparisons between more than two conditions. Tukey's post‐hoc test was used. Values are mean ± SEM. IF THIS IMAGE HAS BEEN PROVIDED BY OR IS OWNED BY A THIRD PARTY, AS INDICATED IN THE CAPTION LINE, THEN FURTHER PERMISSION MAY BE NEEDED BEFORE ANY FURTHER USE. PLEASE CONTACT WILEY'S PERMISSIONS DEPARTMENT ON PERMISSIONS@WILEY.COM OR USE THE RIGHTSLINK SERVICE BY CLICKING ON THE 'REQUEST PERMISSIONS' LINK ACCOMPANYING THIS ARTICLE. WILEY OR AUTHOR OWNED IMAGES MAY BE USED FOR NON-COMMERCIAL PURPOSES, SUBJECT TO PROPER CITATION OF THE ARTICLE, AUTHOR, AND PUBLISHER. EMBO Mol Med, Volume: 7, Issue: 3, Pages: 259-274, First published: 09 February 2015, DOI: (10.15252/emmm.201404169)