PKBα is required for adipose differentiation of mouse embryonic fibroblasts

Abstract

Protein kinase Bα (PKBα) is a key regulator of metabolism, proliferation and differentiation. We have explored the role of PKBα in adipogenesis using wild-type and PKBα-knockout mouse embryonic fibroblasts (MEFs) and show that lack of PKBα prevents MEF differentiation into adipocytes. Expression of ectopic PKBα in PKBα-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 PKBα-deficient MEFs under the same conditions. Significantly, the regulator of adipogenesis Krüppel-like transcription factor 15 gene expression was downregulated in PKBα-deficient MEFs but could be restored by expressing an active PKBα 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 PKBα-deficient MEFs, and are inhibited by LY294002 treatment during early adipocyte differentiation of 3T3-L1 cells. The results underscore an essential role for PKBα in the transcriptional program required for adipogenesis.