Actomyosin-Mediated Tension Orchestrates Uncoupled Respiration in Adipose Tissues

肌动球蛋白介导的张力协调脂肪组织中的非偶联呼吸

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作者:Kevin M Tharp, Michael S Kang, Greg A Timblin, Jon Dempersmier, Garret E Dempsey, Peter-James H Zushin, Jaime Benavides, Catherine Choi, Catherine X Li, Amit K Jha, Shingo Kajimura, Kevin E Healy, Hei Sook Sul, Kaoru Saijo, Sanjay Kumar, Andreas Stahl

Abstract

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.

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