Blimp-1 in adipose resident Tregs controls adipocyte beiging and obesity
Blimp-1 in adipose resident Tregs controls adipocyte beiging and obesity
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.
Qu Xiaoyao、Marrero Giovanni J.、Fooks Allen N.、Helfrich Katherine E.、Poholek Amanda C.、Frias Adolfo B. Jr.、Sipula Ian、Xie Bingxian、Beppu Lisa Y.、Watkins Simon C.、Jurczak Michael J.、D?ˉCruz Louise M.
Department of Immunology, University of PittsburghDepartment of Immunology, University of PittsburghDepartment of Immunology, University of PittsburghCenter for Biologic Imaging, University of PittsburghDepartment of Pediatrics, University of PittsburghDepartment of Immunology, University of PittsburghDivison of Endocrinology, Department of Medicine and the Center for Metabolism and Mitochondrial Medicine, University of PittsburghDivison of Endocrinology, Department of Medicine and the Center for Metabolism and Mitochondrial Medicine, University of PittsburghDepartment of Immunology, University of PittsburghCenter for Biologic Imaging, University of PittsburghDivison of Endocrinology, Department of Medicine and the Center for Metabolism and Mitochondrial Medicine, University of PittsburghDepartment of Immunology, University of Pittsburgh
基础医学生理学分子生物学
Qu Xiaoyao,Marrero Giovanni J.,Fooks Allen N.,Helfrich Katherine E.,Poholek Amanda C.,Frias Adolfo B. Jr.,Sipula Ian,Xie Bingxian,Beppu Lisa Y.,Watkins Simon C.,Jurczak Michael J.,D?ˉCruz Louise M..Blimp-1 in adipose resident Tregs controls adipocyte beiging and obesity[EB/OL].(2025-03-28)[2025-04-25].https://www.biorxiv.org/content/10.1101/2019.12.14.874693.点此复制
评论