Identification of a new secretory factor, CCDC3/Favine, in adipocytes and endothelial cells

The vascular system secretes many bioactive factors. In a gene chip database, we searched for novel genes with signal sequences that are specifically expressed in murine aorta, and focused on one gene previously named CCDC3 (NCBI nucleotide entry NM_028804), and we designated as Favine (fat/vessel-derived secretory protein). Northern blot analysis revealed that CCDC3 was expressed abundantly in the aorta and adipose tissues. The mRNA levels of CCDC3 were higher in adipose tissues of obese db/db mice than control mice, and induced during differentiation of rat primary adipocytes. In differentiated adipocytes, CCDC3 mRNA expression was enhanced by insulin and pioglitazone, a PPARgamma agonist, and suppressed by TNF-alpha, isoproterenol and norepinephrine. Transient expression experiments followed by N-terminal amino acid sequence analysis revealed secretion of CCDC3 protein into the culture medium, which was dose-dependently reduced by brefeldin A, an inhibitor of Golgi-mediated secretory pathway. When expressed in COS-7 cells, CCDC3 protein was post-transcriptionally modified with N-glycosylation, and formed a dimer complex. These results indicate that CCDC3 is a protein secreted by adipocytes and endothelial cells, and that its level is regulated both hormonally and nutritionally.