Actomyosin-Mediated Tension Orchestrates Uncoupled Respiration in Adipose Tissues

AttachmentSize
PDF icon 1-s2.0-S1550413118301165-main.pdf3.59 MB
Authors: 
Tharp KM, Kang MS, Timblin GA, Dempersmier J, Dempsey GE, Zushin PH, Benavides J, Choi C, Li CX, Jha AK, Kajimura S, Healy KE, Sul HS, Saijo K, Kumar S, Stahl A.
Journal: 
Cell Metabolism
Publication Date: 
Tue, 2018-03-06
Institutions: 
1 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. 2 UC Berkeley-UCSF Graduate Program in Bioengineering, University of California, Berkeley, Berkeley, CA 94720, USA. 3 Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA. 4 Program for Metabolic Biology, Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA. 5 Department of Bioengineering, University of California, Berkeley, Berkeley, CA 94720, USA. 6 Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143, USA. 7 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; Department of Materials Science and Engineering, University of California, Berkeley, Berkeley, CA 94720, USA. 8 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; Department of Chemical and Biomolecular Engineering, University of California, Berkeley, Berkeley, CA 94720, USA. 9 Program for Metabolic Biology, Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA. Electronic address: [email protected]
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.