Actomyosin-mediated tension orchestrates uncoupled respiration in adipose tissues

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. Adrenergic signaling is viewed as a key regulator of thermogenesis and UCP1-expression in BAT, while also operating as a potent contractile stimulator in muscle. The muscle-like gene expression patterns of UCP1+ adipocytes have previously been utilized as tissue specific markers, but have not been attributed with any functional role. Here, we demonstrate that BAT utilizes actomyosin machinery to generate tensional responses following adrenergic stimulation, similar to muscle tissues. We show that activation of actomyosin mechanics are critical for the acute induction of oxidative metabolism and uncoupled respiration in UCP1+ adipocytes. Additionally, actomyosin-mediated elasticity regulates mechanosensitive transcriptional co-activators, YAP/TAZ, that facilitate the thermogenic capacity of adipocytes. These unappreciated signaling and mechanical mechanisms may inform future strategies to promote the expansion and activation of brown/beige adipocytes. RNAseq was used to compare gene expression between BAT and perigonadal WAT from 22 week-old C57BL/6N mice fed a high-fat diet for 14 weeks (4 replicates per tissue). Additonally, RNAseq was used to compare gene expression in a BAT cell line treated with vehicle control or 100µM Blebbistatin for 24 hours (3 replicates per condition). All data was generated using Illumina HiSeq2500.