Actomyosin-Mediated Tension Orchestrates Uncoupled Respiration in Adipose Tissues

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

doi:10.1016/j.cmet.2018.02.005

Actomyosin-Mediated Tension Orchestrates Uncoupled Respiration in Adipose Tissues

Cell Metab. 2018 Mar 6;27(3):602-615.e4. doi: 10.1016/j.cmet.2018.02.005.

Authors

Affiliations

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.

Keywords: UCP1; YAP/TAZ; actomyosin; beige adipose; brown adipose; mechanobiology; metabolism; oxidative metabolism; thermogenesis; uncoupled respiration.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Actomyosin / physiology*
Adaptor Proteins, Signal Transducing / metabolism
Adipocytes, Beige / cytology
Adipocytes, Beige / metabolism*
Adipocytes, Brown / cytology
Adipocytes, Brown / metabolism*
Adipose Tissue, Beige / metabolism*
Adipose Tissue, Brown / metabolism*
Animals
Cell Cycle Proteins
Cell Respiration
Cells, Cultured
Disease Models, Animal
Homeostasis
Mice
Oxygen / metabolism
Phosphoproteins / metabolism
Signal Transduction
Thermogenesis
Trans-Activators
Uncoupling Protein 1 / metabolism*
YAP-Signaling Proteins

Substances

Adaptor Proteins, Signal Transducing
Cell Cycle Proteins
Phosphoproteins
Trans-Activators
Ucp1 protein, mouse
Uncoupling Protein 1
Wwtr1 protein, mouse
YAP-Signaling Proteins
Yap1 protein, mouse
Actomyosin
Oxygen

Abstract

Publication types

MeSH terms

Substances

Grants and funding