Sequential regulation of diacylglycerol acyltransferase 2 expression by CAAT/Enhancer-binding protein ss(C/EBP ss) and C/EBP alpha during adipogenesis

Victoria A. Payne, Wo-Shing Au, Sarah L. Gray, Edoardo Dalla Nora, Shaikh M. Rahman, Rebecca Sanders, Dirk Hadaschik, Jacob E. Friedman, Stephen O'Rahilly, Justin J. Rochford*

*Corresponding author for this work

    Research output: Contribution to journalArticle

    47 Citations (Scopus)

    Abstract

    Diacylglycerol acyltransferase 2 (DGAT2) catalyzes the final step of triacylglycerol (TG) synthesis. Despite the existence of an alternative acyltransferase (DGAT1), mice lacking DGAT2 have a severe deficiency of TG in adipose tissue, indicating a nonredundant role for this enzyme in adipocyte TG synthesis. We have studied the regulation of DGAT2 expression during adipogenesis. In both isolated murine preadipocytes and 3T3-L1 cells the temporal pattern of DGAT2 expression closely mimicked that of genes whose expression is regulated by CAAT/enhancer-binding protein beta (C/EBP beta). Inhibition of C/EBP beta expression in differentiating preadipocytes reduced DGAT2 expression, and electrophoretic mobility shift assay and chromatin immunoprecipitation experiments identified a promoter element in the DGAT2 gene that is likely to mediate this effect. The importance of C/EBP beta in adipocyte expression of DGAT2 was confirmed by the finding of reduced DGAT2 expression in the adipose tissue of C/EBP beta-null animals. However, DGAT2 expression is maintained at high levels during the later stages of adipogenesis, when C/EBP beta levels decline. We show that, at these later stages of differentiation, C/EBP alpha is capable of substituting for C/EBP beta at the same promoter element. These observations provide novel insight into the transcriptional regulation of DGAT2 expression. Moreover, they further refine the complex and serial roles of the C/EBP family of transcription factors in inducing and maintaining the metabolic properties of mature adipocytes.

    Original languageEnglish
    Pages (from-to)21005-21014
    Number of pages10
    JournalThe Journal of Biological Chemistry
    Volume282
    Issue number29
    Early online date14 May 2007
    DOIs
    Publication statusPublished - 20 Jul 2007

    Keywords

    • adipocyte differentiation
    • mice lacking
    • 3T3-L1 preadipocytes
    • hepatic steaosis
    • gene-expression
    • adipose-tissue
    • ppar-gamma
    • in-vitro
    • beta
    • activation

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