title: Ankrd26 gene disruption enhances adipogenesis of mouse embryonic fibroblasts.
abstract: We previously reported that partial disruption of the Ankrd26 gene in mice leads to hyperphagia and leptin-resistant obesity. To determine whether the Ankrd26 mutation can affect the development of adipocytes, we studied mouse embryo fibroblasts (MEFs) from the mutant mice. We found that Ankrd26(-/-) MEFs have a higher rate of spontaneous adipogenesis than normal MEFs and that adipocyte formation is greatly increased when the cells are induced with troglitazone alone or with a mixture of troglitazone, insulin, dexamethasone, and methylisobutylxanthine. Increased adipogenesis was detected as an increase in lipid droplet formation and in the expression of several markers of adipogenesis. There was an increase in expression of early stage adipogenesis genes such as Krox20, KLF5, C/EBPβ, C/EBPδ, and late stage adipogenesis regulators KLF15, C/EBPα, PPARγ, and aP2. There was also an increase in adipocyte stem cell markers CD34 and Sca-1 and preadipocyte markers Gata2 and Pref-1, indicating an increase in both stem cells and progenitor cells in the mutant MEFs. Furthermore, ERK was found constitutively activated in Anrd26(-/-) MEFs, and the addition of MEK inhibitors to mutant cells blocked ERK activation, decreased adipogenesis induction, and significantly reduced expression of C/EBPδ, KLF15, PPARγ2, CD34, and Pref-1 genes. We conclude that Ankrd26 gene disruption promotes adipocyte differentiation at both the progenitor commitment and differentiation steps and that ERK activation plays a role in this process.
authors.affiliation: Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4264, USA.
authors.forename: Zhaoliang
authors.initials: Z
authors.lastname: Fei
authors.forename: Tapan K
authors.initials: TK
authors.lastname: Bera
authors.forename: Xiufen
authors.initials: X
authors.lastname: Liu
authors.forename: Laiman
authors.initials: L
authors.lastname: Xiang
authors.forename: Ira
authors.initials: I
authors.lastname: Pastan
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
chemical_list: C526207:Ankrd26 protein, mouse; D004268:DNA-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; D014157:Transcription Factors