Caveolae-Associated Protein 3 (Cavin-3) Influences Adipogenesis via TACE-Mediated Pref-1 Shedding.

ABSTRACT

Abnormal adipogenesis regulation is accompanied by a variety of metabolic dysfunctions and disorders. Caveolae play an important role in the regulation of fat production, modulated by caveolae-associated proteins (Cavin-1 to 4). Here, we investigated the role of Cavin-3 in lipogenesis and adipocyte differentiation, as the regulatory functions and roles of Cavin-3 in adipocytes are unknown. A Cavin-3 knockdown/overexpression stable cell line was established, and adipogenesis-related gene and protein expression changes were investigated by real-time quantitative PCR and Western blot analysis, respectively. Additionally, confocal immune-fluorescence microscopy was used to verify the intracellular position of the relevant factors. The results showed that Cavin-3 mRNA and protein expression were elevated, along with physiological factors such as lipid droplet formation, during adipogenesis. Cavin-3 silencing resulted in retarded adipocyte differentiation, and its overexpression accelerated this process. Furthermore, Cavin-3 knockdown resulted in decreased expression of adipogenesis-related genes, such as PPAR-γ, FAS, aP2, and Adipoq, whereas preadipocyte factor-1 (Pref-1) was markedly increased during adipocyte maturation. Overall, Cavin-3 influences caveolar stability and modulates the tumor necrosis factor-alpha-converting enzyme (TACE)-mediated Pref-1 shedding process in both mouse and human adipocytes. The Cavin-3-dependent shedding mechanism appears to be an important process in adipocyte maturation, providing a potential therapeutic target for obesity-related disorders.