PKBα is required for adipose differentiation of mouse embryonic fibroblasts

Protein kinase Bot (PKB alpha.) is a key regulator of metabolism, proliferation and differentiation. We have explored the role of PKB alpha in adipogenesis using wild-type and PKB alpha-knockout mouse embryonic fibroblasts (MEFs) and show that lack of PKBa prevents MEF differentiation into adipocytes. Expression of ectopic PKB alpha in PKB alpha-deficient cells restores adipogenesis. We identified 80 genes whose expression was upregulated in wild-type MEFs during adipogenesis but whose expression was significantly reduced in PKBa-deficient MEFs under the same conditions. Significantly, the regulator of adipogenesis Kruppel-like transcription factor 15 gene expression was downregulated in PKb alpha-deficient MEFs but could be restored by expressing an active PKB alpha in the deficient cells. The level of lipocalin 2, renin 1 and receptor-activity-modifying protein 3 genes expressed by adipose cells was also decreased in PKB alpha-deficient MEFs, and are inhibited by LY294002 treatment during early adipocyte differentiation of 3T3-L1 cells. The results underscore an essential role for PKBa in the transcriptional program required for adipogenesis.