Obesity increases the production of pro-inflammatory mediators from adipose tissue T cells and compromises TCR repertoire diversity: Implications for systemic inflammation and insulin-resistance (87.32)

Abstract

Abstract Yun-Hee Youm, Hyunwon Yang, Bolormaa Vandanmagsar, Jeffrey M. Gimble, Frank Greenway, Randall Mynatt and Vishwa Deep Dixit Emerging evidence suggests that increase in activated T cell populations in adipose tissue may contribute towards obesity-associated inflammation and insulin-resistance. Here we asked whether, 1)the adipose-resident T cells(ARTs) produce cytokines in response to T cell receptor(TCR) ligation. 2)If the extralymphoid ARTs possess unique TCR repertoire compared to lymphoid-resident T cells and if obesity alters the TCR diversity in specific adipose depots. 3)Can specific elimination of T cells regulate inflammation and insulin-action in obesity? We found that obesity reduced the frequency of naïve ART cells in subcutaneous fat and increased the effector-memory cells in visceral fat. The purified ARTs from obese mice had higher frequency of IFNγ+, Granzyme B+ cells and upon TCR ligation, produced pro-inflammatory cytokines and chemokines. Importantly extralymphoid ARTs exhibited markedly restricted TCR diversity and obesity further compromised the TCR repertoire in adipose depots. Collectively, these data establish that ARTs have restricted TCR-Vβ repertoire and T lymphocytes contribute towards the complex proinflammatory microenvironment of adipose tissue in obesity. However,specific depletion of extralymphoid T cells in visceral fat alone is insufficient to reverse obesity associated feed-forward cascade of inflammation and insulin-resistance.