Wang Shu-Na, Li Zhi-Yong, Ling Qi-Sheng, Jing Peng-Fei, Liu Wen-Yu, Zhang Yi-Jie, Zhang Xiu-Ping, Wang Xi-Yuan, Chang Fu-Qiang, Miao Zhu-Wei, Zhao Jing-Xin, Chen Jin, Miao Chao-Yu
Department of Pharmacology, Second Military Medical University (Naval Medical University), Shanghai, China.
Department of Pathology, Faculty of Medical Imaging, Second Military Medical University (Naval Medical University), Shanghai, China.
Diabetes Metab J. 2025 Sep;49(5):1006-1023. doi: 10.4093/dmj.2024.0211. Epub 2025 Jul 23.
Secreted proteins may become therapeutic targets, drugs and biomarkers for aging and disease. This study aimed to establish a novel secreted protein database for adipose tissue under access to food ad libitum (AL) and caloric restriction (CR), and verify a novel adipokine.
Twelve rat chips were used for whole-genome expression in various adipose tissues from AL and CR rats, followed by bioinformatics analysis and experiments in mice, rats, and humans as well as in obesity and diabetes models.
Adipose tissue expression profiles in rat different locations exhibited unique features, and enrichment analysis of differentially expressed genes between CR and AL groups showed CR effects on different adipose tissues. The 1,472 putative secreted proteins were identified, in which 200 genes were highly expressed, constructing a potential adipokines library. Cysteine rich with EGF like domains 2 (CRELD2, also named MESFATIN), whose gene was mesenteric adipose tissue specifically expressed and upregulated by CR in rat chips, was selected and verified as novel adipokine with proving its expression and secretion in in vivo mouse, rat and human and in vitro adipose tissue and adipocyte. CRELD2 secretion increased during adipocyte differentiation, and CRELD2 recombinant protein promoted adipogenesis. Although CRELD2 serum concentration showed no difference between wild-type mice and genetic ob/ob obesity mice or high fat diet induced obesity mice, CRELD2 expression decreased in white adipose tissues of ob/ob mice.
CRELD2 is a new adipokine involved in adipocyte differentiation and adipogenesis. A novel secreted protein database created from multiple adipose depots with CR intervention is helpful for future discovery and research of more secreted proteins.
分泌蛋白可能成为衰老和疾病的治疗靶点、药物及生物标志物。本研究旨在建立一个关于随意进食（AL）和热量限制（CR）条件下脂肪组织的新型分泌蛋白数据库，并验证一种新型脂肪因子。
使用12只大鼠芯片对来自AL和CR大鼠的各种脂肪组织进行全基因组表达分析，随后在小鼠、大鼠和人类以及肥胖和糖尿病模型中进行生物信息学分析和实验。
大鼠不同部位的脂肪组织表达谱呈现独特特征，CR组和AL组之间差异表达基因的富集分析显示CR对不同脂肪组织有影响。共鉴定出1472种假定的分泌蛋白，其中200个基因高表达，构建了一个潜在的脂肪因子库。选择富含半胱氨酸且具有表皮生长因子样结构域2（CRELD2，也称为MESFATIN），其基因在大鼠芯片中于肠系膜脂肪组织中特异性表达且受CR上调，并在体内小鼠、大鼠和人类以及体外脂肪组织和脂肪细胞中证实其表达和分泌后，被验证为新型脂肪因子。CRELD2在脂肪细胞分化过程中分泌增加，且CRELD2重组蛋白促进脂肪生成。尽管野生型小鼠与基因ob/ob肥胖小鼠或高脂饮食诱导的肥胖小鼠之间的CRELD2血清浓度无差异，但ob/ob小鼠白色脂肪组织中的CRELD2表达降低。
CRELD2是一种参与脂肪细胞分化和脂肪生成的新脂肪因子。通过CR干预从多个脂肪库创建的新型分泌蛋白数据库有助于未来发现和研究更多的分泌蛋白。
