Hyunwon Yang^*†‡,1, Yun-Hee Youm^*†,1, Bolormaa Vandanmagsar^*, Anthony Ravussin^*, Jeffrey M. Gimble^§, Frank Greenway^†, Jacqueline M. Stephens^¶, Randall L. Mynatt^† and Vishwa Deep Dixit^*†

^*Laboratory of Neuroendocrine-Immunology and  

^‡Department of Biotechnology, Seoul Women’s University, Seoul, Korea; and  

^§Stem Cell Biology Laboratory,  

^†Pennington Biomedical Research Center, and  

^¶Department of Biological Sciences, Louisiana State University System, Baton Rouge, LA 70808  

Address correspondence and reprint requests to Dr. Vishwa Deep Dixit, Laboratory of Neuroendocrine-Immunology, Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, LA 70808.

¹ H.Y. and Y.-H.Y. contributed equally to this work. 

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-γ⁺, 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-Vβ 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.