Jak-TGFβ cross-talk links transient adipose tissue inflammation to beige adipogenesis
Jak-TGFβ cross-talk links transient adipose tissue inflammation to beige adipogenesis
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DOI：
10.1126/scisignal.aai7838
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发表时间：
2018-04-24
影响因子：
7.3
通讯作者：
Vegiopoulos, Alexandros
中科院分区：
文献类型：
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作者：
Babaei, Rohollah;Schuster, Maximilian;Vegiopoulos, Alexandros
炎症网络的瞬时激活是脂肪组织重塑所必需的，包括响应于刺激的白色脂肪的“布朗宁”，例如。3-肾上腺素能受体激活在此过程中，白色脂肪组织通过募集所谓的米色脂肪细胞获得产热特性。我们研究了影响脂肪祖细胞的下游信号通路，这些通路促进脂肪细胞的从头形成。我们发现，Jak激酶家族通过Stat 3控制脂肪组织微环境中的TGF β信号传导，从而控制成脂定型，这是鼠和人祖细胞的米色脂肪细胞分化所需的功能。Jak/Stat 3通过在核心转录脂肪形成级联反应被激活之前抑制局部Tgfb 3和Tgfb 1表达来抑制TGF β信号传导至转录因子Srf和Smad 3。在基质细胞中，ATGL依赖性脂肪细胞脂解和β 3-肾上腺素能受体刺激诱导的脂肪组织重塑开始时IL-6家族细胞因子的瞬时波触发了该途径的串扰。我们的研究结果提供了对脂肪祖细胞活化的深入了解，并与脂肪组织炎症途径的治疗靶向相关。
The transient activation of inflammatory networks is required for adipose tissue remodeling including the "browning" of white fat in response to stimuli such as. 3-adrenergic receptor activation. In this process, white adipose tissue acquires thermogenic characteristics through the recruitment of so-called beige adipocytes. We investigated the downstream signaling pathways impinging on adipocyte progenitors that promote de novo formation of adipocytes. We showed that the Jak family of kinases controlled TGF beta signaling in the adipose tissue microenvironment through Stat3 and thereby adipogenic commitment, a function that was required for beige adipocyte differentiation of murine and human progenitors. Jak/Stat3 inhibited TGF beta signaling to the transcription factors Srf and Smad3 by repressing local Tgfb3 and Tgfb1 expression before the core transcriptional adipogenic cascade was activated. This pathway cross-talk was triggered in stromal cells by ATGL-dependent adipocyte lipolysis and a transient wave of IL-6 family cytokines at the onset of adipose tissue remodeling induced by beta 3-adrenergic receptor stimulation. Our results provide insight into the activation of adipocyte progenitors and are relevant for the therapeutic targeting of adipose tissue inflammatory pathways.