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Research ArticleArticle

Xenobiotic-Metabolizing Cytochromes P450 in Human White Adipose Tissue: Expression and Induction

Sandrine Ellero, Ghassan Chakhtoura, Corinne Barreau, Sophie Langouët, Chantal Benelli, Luc Penicaud, Philippe Beaune and Isabelle de Waziers
Drug Metabolism and Disposition April 2010, 38 (4) 679-686; DOI: https://doi.org/10.1124/dmd.109.029249
Sandrine Ellero
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Ghassan Chakhtoura
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Corinne Barreau
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Sophie Langouët
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Chantal Benelli
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Luc Penicaud
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Philippe Beaune
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Isabelle de Waziers
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Abstract

Lipophilic pollutants can accumulate in human white adipose tissue (WAT), and the consequences of this accumulation are still poorly understood. Cytochromes P450 (P450s) have recently been found in rat WAT and shown to be inducible through mechanisms similar to those in the liver. The aim of our study was to describe the cytochrome P450 pattern and their induction mechanisms in human WAT. Explants of subcutaneous and visceral WAT and primary culture of subcutaneous adipocytes were used as WAT models, and liver biopsies and primary culture of hepatocytes were used as liver models to characterize P450 expression in both tissues. The WAT and liver models were then treated with typical P450 inducers (rifampicin, phenobarbital, and 2,3,7,8-tetrachlorodibenzo-p-dioxin) and lipophilic pollutants (lindane, prochloraz, and chlorpyrifos), and the effects on P450 expression were studied. P450 expression was considerably lower in WAT than in the liver, except for CYP1B1 and CYP2U1, which were the most highly expressed adipose P450s in all individuals. 2,3,7,8-Tetrachlorodibenzo-p-dioxin and prochloraz induced CYP1A1 and CYP1B1 expression in both tissues. The aryl hydrocarbon receptor was also present in WAT. In contrast, neither phenobarbital nor rifampicin treatment induced CYP2 or CYP3 mRNA in WAT, and constitutive androstane receptor and pregnane X receptor were almost undetectable. These results suggest that the mechanisms by which P450s of family 1 are regulated in the liver are also functional in human WAT, but those regulating CYP2 and CYP3 expression are not.

Footnotes

  • Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.

    doi:10.1124/dmd.109.029249.

  • WAT
    white adipose tissue
    P450
    cytochrome P450
    PB
    phenobarbital
    RIF
    rifampicin
    TCDD
    2,3,7,8-tetrachlorodibenzo-p-dioxin
    CAR
    constitutive androstane receptor
    PXR
    pregnane X receptor
    AhR
    aryl hydrocarbon receptor
    LIND
    lindane
    PRO
    prochloraz
    CPY
    chlorpyrifos
    DMEM
    Dulbecco's modified Eagle's medium
    PCR
    polymerase chain reaction
    DMSO
    dimethyl sulfoxide
    RT
    reverse transcription
    TBP
    TATA-binding protein
    Ct
    cycle threshold
    SVF
    stroma vascular fraction.

    • Received June 30, 2009.
    • Accepted December 24, 2009.
  • Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 38 (4)
Drug Metabolism and Disposition
Vol. 38, Issue 4
1 Apr 2010
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Research ArticleArticle

Xenobiotic-Metabolizing Cytochromes P450 in Human White Adipose Tissue: Expression and Induction

Sandrine Ellero, Ghassan Chakhtoura, Corinne Barreau, Sophie Langouët, Chantal Benelli, Luc Penicaud, Philippe Beaune and Isabelle de Waziers
Drug Metabolism and Disposition April 1, 2010, 38 (4) 679-686; DOI: https://doi.org/10.1124/dmd.109.029249

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Research ArticleArticle

Xenobiotic-Metabolizing Cytochromes P450 in Human White Adipose Tissue: Expression and Induction

Sandrine Ellero, Ghassan Chakhtoura, Corinne Barreau, Sophie Langouët, Chantal Benelli, Luc Penicaud, Philippe Beaune and Isabelle de Waziers
Drug Metabolism and Disposition April 1, 2010, 38 (4) 679-686; DOI: https://doi.org/10.1124/dmd.109.029249
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