Abstract
Protein kinase Balpha (PKBalpha) is a key regulator of metabolism, proliferation and differentiation. We have explored the role of PKBalpha in adipogenesis using wild-type and PKBalpha-knockout mouse embryonic fibroblasts (MEFs) and show that lack of PKBalpha prevents MEF differentiation into adipocytes. Expression of ectopic PKBalpha in PKBalpha-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 PKBalpha-deficient MEFs under the same conditions. Significantly, the regulator of adipogenesis Krüppel-like transcription factor 15 gene expression was downregulated in PKBalpha-deficient MEFs but could be restored by expressing an active PKBalpha 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 PKBalpha-deficient MEFs, and are inhibited by LY294002 treatment during early adipocyte differentiation of 3T3-L1 cells. The results underscore an essential role for PKBalpha in the transcriptional program required for adipogenesis.
MeSH terms
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Acute-Phase Proteins / drug effects
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Acute-Phase Proteins / genetics
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Adipocytes / cytology
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Adipocytes / drug effects
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Adipocytes / physiology*
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Adipogenesis / drug effects
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Adipogenesis / physiology
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Animals
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Basic Helix-Loop-Helix Transcription Factors / drug effects
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Basic Helix-Loop-Helix Transcription Factors / genetics
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Basic Helix-Loop-Helix Transcription Factors / metabolism
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Cell Differentiation / drug effects
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Cell Differentiation / physiology*
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Cell Line
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Cells, Cultured
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Chromones / pharmacology
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Embryo, Mammalian
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Fibroblasts / cytology
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Fibroblasts / drug effects
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Fibroblasts / physiology*
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Gene Expression Profiling
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Intracellular Signaling Peptides and Proteins / drug effects
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Intracellular Signaling Peptides and Proteins / genetics
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Lipocalin-2
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Lipocalins
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Membrane Proteins / drug effects
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Membrane Proteins / genetics
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Mice
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Mice, Knockout
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Morpholines / pharmacology
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Oncogene Proteins / drug effects
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Oncogene Proteins / genetics
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Proto-Oncogene Proteins c-akt / deficiency
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Proto-Oncogene Proteins c-akt / drug effects
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Proto-Oncogene Proteins c-akt / physiology*
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Receptor Activity-Modifying Proteins
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Renin / drug effects
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Renin / genetics
Substances
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Acute-Phase Proteins
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Basic Helix-Loop-Helix Transcription Factors
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Chromones
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Intracellular Signaling Peptides and Proteins
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Lipocalin-2
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Lipocalins
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Membrane Proteins
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Morpholines
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Oncogene Proteins
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Receptor Activity-Modifying Proteins
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Tcf15 protein, mouse
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Lcn2 protein, mouse
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2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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Proto-Oncogene Proteins c-akt
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Renin