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. (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.本研究将温度敏感性肌因子Musclin定义为脂肪产热的负调控因子，其通过在米色脂肪细胞中拮抗转铁蛋白受体1（Tfr1）/蛋白激酶A（PKA）信号通路，加剧雄性小鼠代谢健康的恶化，从而为该内分泌通路的治疗靶向提供了理论框架。(1) 对喂食普通饲料的C57BL/6J野生型小鼠的7种组织（胫前肌（Tibialis anterior, TA）、心脏、肝脏、白色脂肪组织、棕色脂肪组织、小肠（Intestine）、大脑）开展RNA测序分析，本实验未设置生物学重复。(2) 对MCK-Musclin小鼠与对照小鼠在8℃冷暴露1周后的腹股沟白色脂肪组织（inguinal white adipose tissue, iWAT）开展RNA测序分析，每组设置3个生物学重复。(3) 对MCK-Musclin小鼠与对照小鼠在8℃冷暴露1周后的棕色脂肪组织（brown adipose tissue, BAT）开展RNA测序分析，每组设置3个生物学重复。