TGF-β receptor 1 regulates progenitors that promote browning of white fat.
TGF-β receptor 1 regulates progenitors that promote browning of white fat.
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DOI：
10.1016/j.molmet.2018.07.008
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发表时间：
2018-10
影响因子：
8.1
通讯作者：
Rane SG
中科院分区：
文献类型：
--
作者：
Wankhade UD;Lee JH;Dagur PK;Yadav H;Shen M;Chen W;Kulkarni AB;McCoy JP;Finkel T;Cypess AM;Rane SG
米色/米色脂肪组织显示出棕色脂肪组织的形态特征和有益的代谢特征。以前，我们发现TGF-β信号调节白色脂肪组织的布朗宁。在此，我们探究了TGF-β信号是否调节白色脂肪中假定的米色祖细胞，并研究了涉及米色脂肪形成的TGF-β调节机制。我们删除了脂肪组织中的TGF-β受体1（TβRI）（TβRIAdKO小鼠），并使用基于流式细胞术的分析，鉴定和分离了位于白色脂肪基质血管细胞中的假定米色祖细胞。对这些细胞进行分子表征，以检查米色/棕色标志物表达并研究TGF-β依赖性机制。此外，将细胞移植到无胸腺裸鼠中以检查其脂肪生成潜力。TβRI的缺失促进米色脂肪形成，同时减少高脂饮食喂养的不利影响。TGF-β信号传导与前列腺素途径的相互作用调节了白色脂肪中米色脂肪细胞的出现。使用流式细胞术技术和来自白色脂肪的基质血管部分，我们分离出假定的米色干/祖细胞（iBSC）。在TGF-β信号传导的遗传或药理学抑制后，这些细胞表达高水平的主要米色标志物。将Tβ RI缺陷的基质血管细胞或iBSC移植到无胸腺裸鼠中，然后通过高脂饮食喂养和通过CL 316，243注射或冷暴露刺激β-肾上腺素能信号传导，促进了体内稳健的米色脂肪形成。TβRI信号靶向前列腺素网络，以调节白色脂肪中假定的米色祖细胞，其能够发育成具有功能属性的米色脂肪细胞。控制性抑制TβRI信号传导和伴随的PGE 2刺激有可能促进米色脂肪形成并改善代谢。Wankhade等人显示脂肪组织中TβRI的缺失促进米色脂肪形成。TGF-β和前列腺素途径之间的相互作用调节白色脂肪中推定的祖细胞，其发育成具有功能属性的米色脂肪细胞。这些发现为调节米色脂肪形成的信号提供了机制性见解。脂肪组织中TβRI的缺失促进米色脂肪形成。TβRI调节白色脂肪中假定的米色脂肪祖细胞米色脂肪形成过程中TβRI信号与PGE 2/Cox 2通路相互作用TβRI调节产热、线粒体生物能量学和米色脂肪生成。
Beige/brite adipose tissue displays morphological characteristics and beneficial metabolic traits of brown adipose tissue. Previously, we showed that TGF-β signaling regulates the browning of white adipose tissue. Here, we inquired whether TGF-β signals regulated presumptive beige progenitors in white fat and investigated the TGF-β regulated mechanisms involved in beige adipogenesis. We deleted TGF-β receptor 1 (TβRI) in adipose tissue (TβRIAdKO mice) and, using flow-cytometry based assays, identified and isolated presumptive beige progenitors located in the stromal vascular cells of white fat. These cells were molecularly characterized to examine beige/brown marker expression and to investigate TGF-β dependent mechanisms. Further, the cells were transplanted into athymic nude mice to examine their adipogenesis potential. Deletion of TβRI promotes beige adipogenesis while reducing the detrimental effects of high fat diet feeding. Interaction of TGF-β signaling with the prostaglandin pathway regulated the appearance of beige adipocytes in white fat. Using flow cytometry techniques and stromal vascular fraction from white fat, we isolated presumptive beige stem/progenitor cells (iBSCs). Upon genetic or pharmacologic inhibition of TGF-β signaling, these cells express high levels of predominantly beige markers. Transplantation of TβRI-deficient stromal vascular cells or iBSCs into athymic nude mice followed by high fat diet feeding and stimulation of β-adrenergic signaling via CL316,243 injection or cold exposure promoted robust beige adipogenesis in vivo. TβRI signals target the prostaglandin network to regulate presumptive beige progenitors in white fat capable of developing into beige adipocytes with functional attributes. Controlled inhibition of TβRI signaling and concomitant PGE2 stimulation has the potential to promote beige adipogenesis and improve metabolism. Wankhade et al. show that loss of TβRI in adipose tissue promotes beige adipogenesis. Interaction between the TGF-β and prostaglandin pathways regulates presumptive progenitors in white fat that develop into beige adipocytes with functional attributes. These findings provide mechanistic insight into signals regulating beige adipogenesis. Loss of TβRI in adipose tissue promotes beige adipogenesis. TβRI regulates presumptive beige adipocyte progenitors in white fat. TβRI signals interact with the PGE2/Cox2 pathway during beige adipogenesis. TβRI regulates thermogenesis, mitochondrial bioenergetics and beige adipogenesis.
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影响因子：
64.5
作者：
Goessling W;North TE;Loewer S;Lord AM;Lee S;Stoick-Cooper CL;Weidinger G;Puder M;Daley GQ;Moon RT;Zon LI
通讯作者：
Zon LI
影响因子：
16.6
作者：
Berry DC;Jiang Y;Graff JM
通讯作者：
Graff JM
DOI：
10.1073/pnas.2536828100
发表时间：
2003-12-23
影响因子：
11.1
作者：
He, WM;Barak, Y;Evans, RM
通讯作者：
Evans, RM
影响因子：
2.9
作者：
Fain, JN;Ballou, LR;Bahouth, SW
通讯作者：
Bahouth, SW
影响因子：
29
作者：
Eguchi J;Wang X;Yu S;Kershaw EE;Chiu PC;Dushay J;Estall JL;Klein U;Maratos-Flier E;Rosen ED
通讯作者：
Rosen ED