title: The immune cell transcription factor T-bet: A novel metabolic regulator.
abstract: Obesity-associated insulin resistance is accompanied by an alteration in the Th1/Th2 balance in adipose tissue. T-bet (Tbx21) is an immune cell transcription factor originally described as the master regulator of Th1 cell development, although is now recognized to have a role in both the adaptive and innate immune systems. T-bet also directs T-cell homing to pro-inflammatory sites by the regulation of CXCR3 expression. T-bet(-/-) mice have increased visceral adiposity but are more insulin-sensitive, exhibiting reduced immune cell content and cytokine secretion specifically in the visceral fat depot, perhaps due to altered T-cell trafficking. Studies of T-bet deficiency on Rag2-- and IFN-γ-deficient backgrounds indicate the importance of CD4(+) T cells and IFN-γ in this model. This favorable metabolic phenotype, uncoupling adiposity from insulin resistance, is present in young lean mice yet persists with age and increasing obesity. We suggest a novel role for T-bet in metabolic regulation.
authors.affiliation: Division of Diabetes and Nutritional Sciences; Department of Experimental Immunobiology; King's College London; London, UK.
authors.forename: Emilie
authors.initials: E
authors.lastname: Stolarczyk
authors.affiliation: Department of Experimental Immunobiology; King's College London; London, UK.
authors.forename: Graham M
authors.initials: GM
authors.lastname: Lord
authors.affiliation: Division of Diabetes and Nutritional Sciences; Department of Experimental Immunobiology; King's College London; London, UK.
authors.forename: Jane K
authors.initials: JK
authors.lastname: Howard
keywords: IFN-γ; T-bet; Th1; adipose; diabetes; immune; immunometabolism; inflammation; insulin resistance; metabolism; obesity