Different Roles Of Protein Kinase C-βΙ And -δ In The Regulation Of Adipocyte Differentiation

Protein kinase C (PKC) is a member of serine/threonine protein kinase family that plays important roles in the control of vast variety of cellular functions. Nevertheless, the regulatory effect of PKC on adipogenesis remained not well understood. In this study, we investigated the effect of several PKC isoforms on the adipogenic conversion of 3T3-L1 preadipocytes induced by dexamethasone, isobutylmethylxanthine and insulin. Treatment of cells with broad-spectrum PKC inhibitor R?318220 suppressed the adipogenesis. G?6976, a selective inhibitor for PKC isoformsα,βΙandμ, also inhibited the adipogenesis of cells. Pretreatment of cells with peroxisomal proliferator activated receptor-γ(PPARγ) agonist troglitazone abolished the inhibitory effect of G?6976 on adipogenesis. The plasmic membrane translocation of PKC-βΙwas observed at the first two days of differentiation. Whereas no translocation of PKC-αand -μwas observed. Overexpression of dominant negative PKC-βΙ, but not wild-type PKC-βΙ, blocked adipogenesis. This effect of dominant negative PKC-βΙcan be reversed by troglitazone, suggesting that PKC-βΙis required for the initiation of adipogenesis. In addition, rottlerin, a specific inhibitor of PKC-δ, can reverse the suppression of adipogenesis mediated by 12-O-tetradecanoyl-phorbol-13-acetate, transforming growth factorβ1, and epidermal growth factor. These data suggest that PKC-βΙis important in the induction of adipogenesis, while the PKC-δhas an inhibitory role for adipogenesis.