Bioenergetic responses to β-adrenergic stimulation in beige adipocyte depend on actomyosin driven forces

Abstract

Beige (BeAT) and white adipoctyes (WAT) reside within the same fat depots but differ in their responses to {beta}-adrenergic stimulation. While both activate classical PKA-mediated pathways, only beige adipocytes show induction of UCP1 expression and enhanced mitochondrial respiration, suggesting additional mechanisms that distinguish their responses. Here we uncover a parallel, non-canonical biomechanical pathway specific to beige adipocytes that is essential for thermogenic activation. Mechanistically, {beta}-AR stimulation induces a rapid Myh9-mediated actomyosin contraction and stiffening in beige, but not white, adipocytes that activates focal adhesion kinase (FAK), which we show to be critical for the expression of oxidative and thermogenic genes including UCP1 and PLIN5. These findings reveal a new biomechanical Myh9-FAK signaling arm downstream of b-adrenergic activation that differentiates thermogenic from white adipocytes.