Obesity Increases the Production of Proinflammatory Mediators from Adipose Tissue T Cells and Compromises TCR Repertoire Diversity: Implications for Systemic Inflammation and Insulin Resistance

2010/06/26 by Hyunwon Yang, Yun‐Hee Youm, Yun-Hee Youm +11 · 442 citations
Immunology and Microbiology · Medicine · #Adipokines, Inflammation, and Metabolic Diseases #Adipose tissue #Atherosclerosis and Cardiovascular Diseases #Biology #Endocrinology #Immune Cell Function and Interaction #Immune system #Immunology #Inflammation #Insulin #Insulin resistance #Internal medicine #Medicine #Proinflammatory cytokine #Systemic inflammation #T cell #T-cell receptor

paper · doi:10.4049/jimmunol.1000021

published in The Journal of Immunology 185(3), 1836-1845 (American Association of Immunologists)

openalex publication_date 2010/06/26 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01

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.

Citations

• Leptin in Immunology

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