title: Obesity increases the production of proinflammatory mediators from adipose tissue T cells and compromises TCR repertoire diversity: implications for systemic inflammation and insulin resistance.
abstract: Emerging evidence suggests that increases in activated T cell populations in adipose tissue may contribute toward obesity-associated metabolic syndrome. The present study investigates three unanswered questions: 1) Do adipose-resident T cells (ARTs) from lean and obese mice have altered cytokine production in response to TCR ligation?; 2) Do the extralymphoid ARTs possess a unique TCR repertoire compared with lymphoid-resident T cells and whether obesity alters the TCR diversity in specific adipose depots?; and 3) Does short-term elimination of T cells in epididymal fat pad without disturbing the systemic T cell homeostasis regulate inflammation and insulin-action during obesity? We found that obesity reduced the frequency of naive ART cells in s.c. fat and increased the effector-memory populations in visceral fat. The ARTs from diet-induced obese (DIO) mice had a higher frequency of IFN-gamma(+), granzyme B(+) cells, and upon TCR ligation, the ARTs from DIO mice produced increased levels of proinflammatory mediators. Importantly, compared with splenic T cells, ARTs exhibited markedly restricted TCR diversity, which was further compromised by obesity. Acute depletion of T cells from epididymal fat pads improved insulin action in young DIO mice but did not reverse obesity-associated feed forward cascade of chronic systemic inflammation and insulin resistance in middle-aged DIO mice. Collectively, these data establish that ARTs have a restricted TCR-Vbeta repertoire, and T cells contribute toward the complex proinflammatory microenvironment of adipose tissue in obesity. Development of future long-term T cell depletion protocols specific to visceral fat may represent an additional strategy to manage obesity-associated comorbidities.
authors.affiliation: Laboratory of Neuroendocrine-Immunology, Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, LA 70808, USA.
authors.forename: Hyunwon
authors.initials: H
authors.lastname: Yang
authors.forename: Yun-Hee
authors.initials: YH
authors.lastname: Youm
authors.forename: Bolormaa
authors.initials: B
authors.lastname: Vandanmagsar
authors.forename: Anthony
authors.initials: A
authors.lastname: Ravussin
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Gimble
authors.forename: Frank
authors.initials: F
authors.lastname: Greenway
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Stephens
authors.forename: Randall L
authors.initials: RL
authors.lastname: Mynatt
authors.forename: Vishwa Deep
authors.initials: VD
authors.lastname: Dixit
mesh_terms: D000273:Adipose Tissue / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D016516:CD4-CD8 Ratio; D002478:Cells, Cultured; D004032:Diet / Q000009:adverse effects; D005260:Female; D005951:Glucose Tolerance Test / Q000379:methods; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D018836:Inflammation Mediators / Q000378:metabolism* / Q000502:physiology; D007333:Insulin Resistance / Q000276:immunology*; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D050507:Subcutaneous Fat, Abdominal / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation / Q000276:immunology
chemical_list: D018836:Inflammation Mediators; D011948:Receptors, Antigen, T-Cell