title: Autoimmunity to HSP60 during diet induced obesity in mice.
abstract: Adaptive immunity has been implicated in adipose tissue inflammation, obesity and its adverse metabolic consequences. No obesity-related autoantigen has yet been identified, although heat shock protein 60 (HSP60) has been implicated in other autoimmune diseases. We investigated whether feeding a high-fat diet to C57BL/6J mice would cause autoimmunity to HSP60 and whether immunomodulation with peptides from HSP60 would reverse the resulting obesity or metabolic dysfunction. Obese mice had higher circulating levels of HSP60 associated with increased T-lymphocyte proliferation responses and the emergence of circulating IgG1 and IgG2c antibody levels against HSP60. Treatment with escalating doses of a mixture of three proven immunomodulatory HSP60 peptides did not reduce weight but completely reversed the increase in VLDL/LDL levels and partially reversed the glucose intolerance in obese mice. Obese mice mount an autoimmune response to HSP60, which partly underlies the resulting metabolic disturbances.
authors.affiliation: School of Clinical Sciences and Bristol Heart Institute, Bristol Royal Infirmary, University of Bristol, Bristol, UK.
authors.forename: M E
authors.initials: ME
authors.lastname: Şelli
authors.affiliation: Laboratory of Autoimmunity, Division for Experimental Pathology and Immunology, Biocenter Innsbruck Medical University, Innsbruck, Austria.
authors.forename: G
authors.initials: G
authors.lastname: Wick
authors.affiliation: School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK.
authors.forename: D C
authors.initials: DC
authors.lastname: Wraith
authors.affiliation: School of Clinical Sciences and Bristol Heart Institute, Bristol Royal Infirmary, University of Bristol, Bristol, UK.
authors.forename: A C
authors.initials: AC
authors.lastname: Newby
mesh_terms: D000273:Adipose Tissue / Q000276:immunology; D000818:Animals; D015551:Autoimmunity / Q000187:drug effects / Q000276:immunology*; D018834:Chaperonin 60 / Q000097:blood / Q000276:immunology* / Q000494:pharmacology; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D008659:Metabolic Diseases / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000097:blood / Q000276:immunology* / Q000494:pharmacology; D009765:Obesity / Q000209:etiology / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: D018834:Chaperonin 60; C557066:Hspd1 protein, mouse; D024101:Mitochondrial Proteins