组织器官间的互作和信息交流是糖脂代谢研究新热点，肌肉分泌的多种肌肉因子的代谢调控作用陆续被揭示。申请人预研究发现：肌肉特异性敲除组蛋白甲基化酶G9a小鼠可抵抗高脂诱导的肥胖及非酒精性脂肪肝；RNA-seq显示肌肉敲除G9a可引起肌肉素等多个肌肉因子的表达水平变化；以肌肉素为例，向高脂诱导的肥胖小鼠注射肌肉素或其核心肽段，均可减少肝脏和白色脂肪的脂质病变。申请人据此提出“肌肉中的G9a通过调控肌肉素等肌肉因子影响机体代谢平衡”研究假说。本项目拟深入研究①肌肉中G9a调控肌肉素等肌肉因子表达的分子机制；②肌肉素通过自/内分泌来抑制高脂引起的代谢紊乱的机理；③研究RNA-seq发现的其它肌肉因子能否调控组织器官代谢稳态，是否与肌肉素有协同作用。本项目有望揭示G9a在“肌肉-肝脏-脂肪”代谢轴中所起作用，提供维系组织器官间代谢网络的部分新数据，为相关疾病临床防治提供理论和实践依据。

The interaction and information exchange between tissues and organs have become a hotspot in the research field of metabolism. Recent studies have revealed the metabolic regulation roles of a number of myokines. In pilot studies carried out by the applicant, we have obtained some interesting findings. Muscle-specific knockout histone methyltransferase G9a mice were resistant to high fat-induced obesity and nonalcoholic fatty liver disease; RNA-seq results showed that muscle knockout of G9a caused alterations of multiple myokines including musclin. Injection of full-length or core peptide fragment of musclin into high fat-induced obese mice can reduce pathological lesions in the liver and white fat. Based on these novel observations, the applicant proposed a working hypothesis that 'G9a in muscle affects the metabolic balance by regulating certain myokines such as musclin’. This project intends to thoroughly investigate: ① Underlying molecular mechanism of how G9a regulates myokines expression in muscles; ② Mechanism of how musclin inhibits the high fat diet-induced metabolic disorders through auto/endocrine; ③ Can other myokines identified by RNA-seq regulate the metabolic homeostasis? And whether it has a synergical effect with musclin? This project is expected to reveal the role of G9a in the “muscle-liver-adipose tissue” metabolic axis, and provides some novel data on how metabolic network between tissues and organs are maintained, theoretical and practical foundations for relevant clinical transformation studies are also expected.