Blimp-1 in adipose resident Tregs controls adipocyte beiging and obesity

Beppu, L. Y.; Qu, X.; Marrero, G. J.; Fooks, A. N.; Frias, A. B.; Helfrich, K. E.; Sipula, I.; Xie, B.; Watkins, S. C.; Poholek, A. C.; Jurczak, M. J.; D'Cruz, L. M.

doi:10.1101/2019.12.14.874693

bioRxiv · 10.1101/2019.12.14.874693

Blimp-1 in adipose resident Tregs controls adipocyte beiging and obesity

Beppu, L. Y.·Qu, X.·Marrero, G. J.·Fooks, A. N.·Frias, A. B.·Helfrich, K. E.·Sipula, I.·Xie, B.·Watkins, S. C.·Poholek, A. C.·Jurczak, M. J.·D'Cruz, L. M.

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Abstract

Crosstalk between the immune system and adipocytes is critical for maintaining tissue homeostasis and regulating chronic systemic inflammation during diet-induced obesity (DIO). How visceral adipose tissue resident regulatory T cells (aTregs) signal to adipocytes in the visceral adipose tissue (VAT) is not understood. Here we show that Treg-specific ablation of the transcriptional regulator Blimp-1 resulted in increased insulin sensitivity, decreased body weight and increased Ucp-1 in adipocytes in high fat diet (HFD)-fed mice. Mechanistically, we demonstrate that Blimp-1 drives IL-10 production in Tregs, thus suppressing beiging and energy expenditure in adipocytes. Moreover, IL-10 mRNA expression positively correlated with increasing body weight in humans. These findings reveal a surprising relationship between aTregs and adipocytes in promoting insulin resistance during excessive caloric intake, placing Blimp-1-regulated IL-10 expression by aTregs at a critical juncture in the development of obesity and its associated comorbidities in mice and humans. SUMMARYHere we show that ablation of Blimp-1 in adipose tissue resident Tregs (aTregs) leads to decreased IL-10 production, resulting in increased Ucp-1 expression and beiging by adipocytes and protection from diet-induced obesity and insulin resistance.

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Beppu, L. Y., Qu, X., Marrero, G. J., Fooks, A. N., Frias, A. B., Helfrich, K. E., Sipula, I., Xie, B., Watkins, S. C., Poholek, A. C., Jurczak, M. J., D'Cruz, L. M.. 2019-12-14. Blimp-1 in adipose resident Tregs controls adipocyte beiging and obesity. https://doi.org/10.1101/2019.12.14.874693

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