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.

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
  • Uncoupling Protein 1 / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • Phosphoproteins
  • Ucp1 protein, mouse
  • Uncoupling Protein 1
  • Wwtr1 protein, mouse
  • Yap protein, mouse
  • Actomyosin
  • Oxygen