title: Different Th17 immunity in gut, liver, and adipose tissues during obesity: the role of diet, genetics, and microbes.
abstract: Microbes modify immunometabolism responses linking obesity and type 2 diabetes. Immunity helps maintain a host-microbe symbiosis, but inflammation can promote insulin resistance in tissues that control blood glucose. We were interested in compartmentalization of immune responses during obesity and show here that feeding mice an obesity-causing high-fat diet (HFD) decreased a marker of neutrophil activation and cytokines related to Th17 responses in the gut. A HFD decreased IL-17 and IL-21/22 in the ileum and colon, respectively. A HFD increased IL-17, IL-21/22 and other related Th17 responses in the liver. At the whole tissue level, there is divergence in gut and metabolic tissue Th17 cytokines during diet-induced obesity. Deletion of the bacterial peptidoglycan sensor NOD2 had relatively minor effects on these immune responses. We propose a model where diet-induced obesity promotes a permissive gut immune environment and sets the stage for host genetics to contribute to dysbiosis-driven metabolic tissue inflammation.
authors.affiliation: a Department of Biochemistry and Biomedical Sciences , McMaster University , Hamilton , ON , Canada.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Cavallari
authors.affiliation: a Department of Biochemistry and Biomedical Sciences , McMaster University , Hamilton , ON , Canada.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Denou
authors.affiliation: a Department of Biochemistry and Biomedical Sciences , McMaster University , Hamilton , ON , Canada.
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Foley
authors.affiliation: b Department of Pathology and Molecular Medicine , McMaster University , Hamilton , ON , Canada.|c Farncombe Family Digestive Health Research Institute, McMaster University , Hamilton , ON , Canada.
authors.forename: Waliul I
authors.initials: WI
authors.lastname: Khan
authors.affiliation: a Department of Biochemistry and Biomedical Sciences , McMaster University , Hamilton , ON , Canada.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Schertzer
mesh_terms: D000273:Adipose Tissue / Q000276:immunology*; D000818:Animals; D016207:Cytokines / Q000276:immunology; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology / Q000382:microbiology; D059305:Diet, High-Fat; D000069196:Gastrointestinal Microbiome / Q000276:immunology*; D041981:Gastrointestinal Tract / Q000276:immunology* / Q000473:pathology*; D008099:Liver / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018375:Neutrophil Activation / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D053473:Nod2 Signaling Adaptor Protein / Q000172:deficiency* / Q000235:genetics; D009765:Obesity / Q000276:immunology* / Q000382:microbiology; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D016207:Cytokines; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse
keywords: diabetes; glucose; high fat diet; immunometabolism; insulin resistance; metabolic endotoxemia; microbiota; peptidoglycan