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Cell Press, Cell Metabolism, 4(17), p. 520-533, 2013

DOI: 10.1016/j.cmet.2013.02.019

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Improved Insulin Sensitivity despite Increased Visceral Adiposity in Mice Deficient for the Immune Cell Transcription Factor T-bet

Journal article published in 2013 by Emilie Stolarczyk, Chi Teng Vong, Esperanza Perucha ORCID, Ian Jackson, Michael A. Cawthorne, Edward T. Wargent, Nick Powell ORCID, James B. Canavan, Graham M. Lord ORCID, Jane K. Howard ORCID
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Abstract

Low-grade inflammation in fat is associated with insulin resistance, although the mechanisms are unclear. We report that mice deficient in the immune cell transcription factor T-bet have lower energy expenditure and increased visceral fat compared with wild-type mice, yet paradoxically are more insulin sensitive. This striking phenotype, present in young T-bet(-/-) mice, persisted with high-fat diet and increasing host age and was associated with altered immune cell numbers and cytokine secretion specifically in visceral adipose tissue. However, the favorable metabolic phenotype observed in T-bet-deficient hosts was lost in T-bet(-/-) mice also lacking adaptive immunity (T-bet(-/-)xRag2(-/-)), demonstrating that T-bet expression in the adaptive rather than the innate immune system impacts host glucose homeostasis. Indeed, adoptive transfer of T-bet-deficient, but not wild-type, CD4(+) T??cells to Rag2(-/-) mice improved insulin sensitivity. Our results reveal a role for T-bet in metabolic physiology and obesity-associated insulin resistance.