A PPAR response element regulates transcription of the gene for human adipose differentiation-related protein

Paul Targett-Adams (Lead / Corresponding author), Marion J. McElwee, Ewa Ehrenborg, Mattias C. Gustafsson, Colin N. Palmer, John McLauchlan

    Research output: Contribution to journalArticlepeer-review

    81 Citations (Scopus)

    Abstract

    Lipid droplets are cytoplasmic organelles which serve as storage sites for neutral lipids. Adipose differentiation-related protein (ADRP) is intrinsically associated with the surface of lipid droplets and is believed to play a major role in the maintenance of lipid stores in non-adipocytes. ADRP abundance is intimately linked to the amount of lipid found within cells and agents which increase the levels of intracellular lipid, such as certain agonists of the peroxisome proliferator-activated receptors (PPARs), also are capable of modulating ADRP gene transcription. However, little is known about the molecular mechanisms and promoter control elements, which regulate the transcription of the human gene. Using a reporter system to investigate ADRP transcription, we have identified a PPAR response element (PPRE) with the sequence 5′-AGGTGA A AGGGCG-3′ within its promoter region. Mutational analysis revealed that the ADRP PPRE specifically mediated the upregulation of transcription in response to activation by agonists of PPAR subtypes α and δ in both rat and human hepatocyte-derived cell lines. These findings offer insight into the mechanisms which serve to regulate ADRP transcription and intracellular lipid storage.

    Original languageEnglish
    Pages (from-to)95-104
    Number of pages10
    JournalBiochimica et Biophysica Acta - Gene Structure and Expression
    Volume1728
    Issue number1-2
    Early online date16 Feb 2005
    DOIs
    Publication statusPublished - 5 Apr 2005

    Keywords

    • ADRP
    • PPAR
    • PPRE
    • Promoter
    • Regulation

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