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

    46 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

    Cite this

    Sequential regulation of diacylglycerol acyltransferase 2 expression by CAAT/Enhancer-binding protein ss(C/EBP ss) and C/EBP alpha during adipogenesis. / Payne, Victoria A.; Au, Wo-Shing; Gray, Sarah L.; Nora, Edoardo Dalla; Rahman, Shaikh M.; Sanders, Rebecca; Hadaschik, Dirk; Friedman, Jacob E.; O'Rahilly, Stephen; Rochford, Justin J.

    In: The Journal of Biological Chemistry, Vol. 282, No. 29, 20.07.2007, p. 21005-21014.

    Research output: Contribution to journalArticle

    Payne, Victoria A. ; Au, Wo-Shing ; Gray, Sarah L. ; Nora, Edoardo Dalla ; Rahman, Shaikh M. ; Sanders, Rebecca ; Hadaschik, Dirk ; Friedman, Jacob E. ; O'Rahilly, Stephen ; Rochford, Justin J. / Sequential regulation of diacylglycerol acyltransferase 2 expression by CAAT/Enhancer-binding protein ss(C/EBP ss) and C/EBP alpha during adipogenesis. In: The Journal of Biological Chemistry. 2007 ; Vol. 282, No. 29. pp. 21005-21014.
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    title = "Sequential regulation of diacylglycerol acyltransferase 2 expression by CAAT/Enhancer-binding protein ss(C/EBP ss) and C/EBP alpha during adipogenesis",
    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.",
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    author = "Payne, {Victoria A.} and Wo-Shing Au and Gray, {Sarah L.} and Nora, {Edoardo Dalla} and Rahman, {Shaikh M.} and Rebecca Sanders and Dirk Hadaschik and Friedman, {Jacob E.} and Stephen O'Rahilly and Rochford, {Justin J.}",
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    T1 - Sequential regulation of diacylglycerol acyltransferase 2 expression by CAAT/Enhancer-binding protein ss(C/EBP ss) and C/EBP alpha during adipogenesis

    AU - Payne, Victoria A.

    AU - Au, Wo-Shing

    AU - Gray, Sarah L.

    AU - Nora, Edoardo Dalla

    AU - Rahman, Shaikh M.

    AU - Sanders, Rebecca

    AU - Hadaschik, Dirk

    AU - Friedman, Jacob E.

    AU - O'Rahilly, Stephen

    AU - Rochford, Justin J.

    PY - 2007/7/20

    Y1 - 2007/7/20

    N2 - 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.

    AB - 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.

    KW - adipocyte differentiation

    KW - mice lacking

    KW - 3T3-L1 preadipocytes

    KW - hepatic steaosis

    KW - gene-expression

    KW - adipose-tissue

    KW - ppar-gamma

    KW - in-vitro

    KW - beta

    KW - activation

    U2 - 10.1074/jbc.M702871200

    DO - 10.1074/jbc.M702871200

    M3 - Article

    VL - 282

    SP - 21005

    EP - 21014

    JO - The Journal of Biological Chemistry

    JF - The Journal of Biological Chemistry

    SN - 0021-9258

    IS - 29

    ER -