Actomyosin-Mediated Tension Orchestrates Uncoupled Respiration in Adipose Tissues

Publication date: 6 March 2018
Source:Cell Metabolism, Volume 27, Issue 3
Author(s): 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
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.

Graphical abstract

Teaser

Tharp et al. show that brown adipocytes engage tensional actomyosin machinery, similar to muscle tissues, following adrenergic stimulation to mediate the thermogenic program and normal BAT function. These effects are mechanistically mediated through the YAP/TAZ pathway and, on a broad level, highlight the importance of cellular mechanics for cell metabolism.


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