肌球蛋白介导的张力协调脂肪组织中的解偶联呼吸。
Actomyosin-Mediated Tension Orchestrates Uncoupled Respiration in Adipose Tissues.
机构信息
Program for Metabolic Biology, Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Bioengineering, University of California, Berkeley, Berkeley, CA 94720, USA.
UC Berkeley-UCSF Graduate Program in Bioengineering, University of California, Berkeley, Berkeley, CA 94720, USA.
出版信息
Cell Metab. 2018 Mar 6;27(3):602-615.e4. doi: 10.1016/j.cmet.2018.02.005.
The activation of brown/beige adipose tissue (BAT) metabolism and the induction of uncoupling protein 1 (UCP1) expression are essential for BAT-based strategies to improve metabolic homeostasis. Here, we demonstrate that BAT utilizes actomyosin machinery to generate tensional responses following adrenergic stimulation, similar to muscle tissues. The activation of actomyosin mechanics is critical for the acute induction of oxidative metabolism and uncoupled respiration in UCP1 adipocytes. Moreover, we show that actomyosin-mediated elasticity regulates the thermogenic capacity of adipocytes via the mechanosensitive transcriptional co-activators YAP and TAZ, which are indispensable for normal BAT function. These biomechanical signaling mechanisms may inform future strategies to promote the expansion and activation of brown/beige adipocytes.
棕色/米色脂肪组织 (BAT) 代谢的激活和解偶联蛋白 1 (UCP1) 的表达诱导对于基于 BAT 的策略改善代谢稳态至关重要。在这里，我们证明 BAT 利用肌动球蛋白机制在肾上腺素刺激后产生紧张反应，类似于肌肉组织。肌动球蛋白力学的激活对于 UCP1 脂肪细胞中氧化代谢和解偶联呼吸的急性诱导至关重要。此外，我们表明肌球蛋白介导的弹性通过机械敏感转录共激活因子 YAP 和 TAZ 调节脂肪细胞的产热能力，YAP 和 TAZ 对于正常的 BAT 功能是不可或缺的。这些生物力学信号机制可能为促进棕色/米色脂肪细胞的扩张和激活提供未来的策略。
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