Regulation of adipose tissue T cell subsets by Stat3 is crucial for diet-induced obesity and insulin resistance

SJ Priceman, M Kujawski, S Shen… - Proceedings of the …, 2013 - National Acad Sciences
SJ Priceman, M Kujawski, S Shen, GA Cherryholmes, H Lee, C Zhang, L Kruper, J Mortimer…
Proceedings of the National Academy of Sciences, 2013National Acad Sciences
Dysregulated inflammation in adipose tissue, marked by increased proinflammatory T-cell
accumulation and reduced regulatory T cells (Tregs), contributes to obesity-associated
insulin resistance. The molecular mechanisms underlying T-cell-mediated inflammation in
adipose tissue remain largely unknown, however. Here we show a crucial role for signal
transducer and activator of transcription 3 (Stat3) in T cells in skewing adaptive immunity in
visceral adipose tissue (VAT), thereby contributing to diet-induced obesity (DIO) and insulin …
Dysregulated inflammation in adipose tissue, marked by increased proinflammatory T-cell accumulation and reduced regulatory T cells (Tregs), contributes to obesity-associated insulin resistance. The molecular mechanisms underlying T-cell-mediated inflammation in adipose tissue remain largely unknown, however. Here we show a crucial role for signal transducer and activator of transcription 3 (Stat3) in T cells in skewing adaptive immunity in visceral adipose tissue (VAT), thereby contributing to diet-induced obesity (DIO) and insulin resistance. Stat3 activity is elevated in obese VAT and in VAT-resident T cells. Functional ablation of Stat3 in T cells reduces DIO, improves insulin sensitivity and glucose tolerance, and suppresses VAT inflammation. Importantly, Stat3 ablation reverses the high Th1/Treg ratio in VAT of DIO mice that is likely secondary to elevated IL-6 production, leading in turn to suppression of Tregs. In addition, Stat3 in T cells in DIO mice affects adipose tissue macrophage accumulation and M2 phenotype. Our study identifies Stat3 in VAT-resident T cells as an important mediator and direct target for regulating adipose tissue inflammation, DIO, and its associated metabolic dysfunctions.
National Acad Sciences