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

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 antagonizing Tfr1/PKA signaling in beige adipocytes, and thus provides a framework for the therapeutic targeting of this endocrine pathway. Overall design: (1) RNA-Seq analysis of 7 tissues (Tibialis anterior (TA) muscle, Heart, Liver, White adipose, Brown adipose, Small intestine (Intestine), Brain) from C57BL/6J wildtype mice fed with chow diet was performed. No biological replicate was included in this RNA-Seq. (2) RNA-Seq analysis of iWAT from MCK-Musclin and control mice following cold exposure at 8oC for 1 week was performed. Three biological replicates in each group were included. (3) RNA-Seq analysis of BAT from MCK-Musclin and control mice following cold exposure at 8oC for 1 week was performed. Three biological replicates in each group were included.