The muscle-enriched myokine Musclin impairs beige fat thermogenesis and systemic energy homeostasis via Tfr1/PKA signaling in male mice

Skeletal muscle and thermogenic adipose tissue are both critical for the maintenance of body temperature in mammals. However, whether these two tissues are interconnected to modulate thermogenesis and metabolic homeostasis in response to thermal stress remains inconclusive. This work defines the temperature sensitive myokine Musclin as a negative regulator of adipose thermogenesis that exacerbates the deterioration of metabolic health in male mice through directly binding to beige fat and antagonizing Tfr1/PKA signaling in beige adipocytes, and thus provides a framework for the therapeutic targeting of this endocrine pathway. In the study, iWAT from C57BL/6J wildtype mice following cold acclimation and control mice housed at room temperature were collected for total RNA extraction and RNA-Seq analysis. The raw data were deposited in this data repository.