title: Adipocytes from New Zealand obese mice exhibit aberrant proinflammatory reactivity to the stress signal heat shock protein 60.
abstract: Adipocytes release immune mediators that contribute to diabetes-associated inflammatory processes. As the stress protein heat shock protein 60 (Hsp60) induces proinflammatory adipocyte activities, we hypothesized that adipocytes of diabetes-predisposed mice exhibit an increased proinflammatory reactivity to Hsp60. Preadipocytes and mature adipocytes from nonobese diabetic (NOD), New Zealand obese (NZO), and C57BL/6J mice were analyzed for Hsp60 binding, Hsp60-activated signaling pathways, and Hsp60-induced release of the chemokine CXCL-1 (KC), interleukin 6 (IL-6), and macrophage chemoattractant protein-1 (MCP-1). Hsp60 showed specific binding to (pre-)adipocytes of NOD, NZO, and C57BL/6J mice. Hsp60 binding involved conserved binding structure(s) and Hsp60 epitopes and was strongest to NZO mouse-derived mature adipocytes. Hsp60 exposure induced KC, IL-6, and MCP-1 release from (pre-)adipocytes of all mouse strains with a pronounced increase of IL-6 release from NZO mouse-derived adipocytes. Compared to NOD and C57BL/6J mouse derived cells, Hsp60-induced formation of IL-6, KC, and MCP-1 from NZO mouse-derived (pre-)adipocytes strongly depended on NF κ B-activation. Increased Hsp60 binding and Hsp60-induced IL-6 release by mature adipocytes of NZO mice suggest that enhanced adipocyte reactivity to the stress signal Hsp60 contributes to inflammatory processes underlying diabetes associated with obesity and insulin resistance.
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, the Heinrich-Heine-University Düsseldorf, Auf'm Hennekamp 65, 40225 Düsseldorf, Germany.
authors.forename: Tina
authors.initials: T
authors.lastname: Märker
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, the Heinrich-Heine-University Düsseldorf, Auf'm Hennekamp 65, 40225 Düsseldorf, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Kriebel
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, the Heinrich-Heine-University Düsseldorf, Auf'm Hennekamp 65, 40225 Düsseldorf, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Wohlrab
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, the Heinrich-Heine-University Düsseldorf, Auf'm Hennekamp 65, 40225 Düsseldorf, Germany ; German Center for Diabetes Research (DZD e.V.), Düsseldorf, Germany.
authors.forename: Volker
authors.identifier: 0000-0002-7309-324X
authors.initials: V
authors.lastname: Burkart
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, the Heinrich-Heine-University Düsseldorf, Auf'm Hennekamp 65, 40225 Düsseldorf, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Habich
mesh_terms: D017667:Adipocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D050156:Adipogenesis; D000818:Animals; D002478:Cells, Cultured; D018834:Chaperonin 60 / Q000235:genetics / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000819:agonists / Q000096:biosynthesis / Q000378:metabolism; D054360:Chemokine CXCL1 / Q000819:agonists / Q000096:biosynthesis / Q000378:metabolism; D016207:Cytokines / Q000819:agonists / Q000096:biosynthesis / Q000378:metabolism*; D005260:Female; D015850:Interleukin-6 / Q000819:agonists / Q000096:biosynthesis / Q000378:metabolism; D050152:Intra-Abdominal Fat / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008820:Mice, Obese; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000819:agonists / Q000378:metabolism; D009765:Obesity / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015434:Panniculitis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D011994:Recombinant Proteins / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C491768:Ccl2 protein, mouse; D018834:Chaperonin 60; D018932:Chemokine CCL2; D054360:Chemokine CXCL1; C475895:Cxcl1 protein, mouse; D016207:Cytokines; C060293:HSPD1 protein, human; D015850:Interleukin-6; D024101:Mitochondrial Proteins; D016328:NF-kappa B; D011994:Recombinant Proteins; C577686:interleukin-6, mouse