Construction of a Novel Secreted Protein Database and Identification of a New Adipokine CRELD2.

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.