Xenobiotic-metabolizing cytochromes p450 in human white adipose tissue: expression and induction.
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.
Ellero
Sandrine
S
Institut National de la Santé et de la Recherche Médicale, Université Paris Descartes, Interdisciplinary Institute of Life Sciences des Saints Péres, Paris, France.
Chakhtoura
Ghassan
G
Barreau
Corinne
C
Langouët
Sophie
S
Benelli
Chantal
C
Penicaud
Luc
L
Beaune
Philippe
P
de Waziers
Isabelle
I
D052438:Adipocytes, White / Q000378:metabolism; D052436:Adipose Tissue, White / Q000201:enzymology / Q000378:metabolism*; D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D015153:Blotting, Western; D002478:Cells, Cultured; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism*; D000072467:Cytochrome P450 Family 2; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D004790:Enzyme Induction / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D000077297:Pregnane X Receptor; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000378:metabolism; D015262:Xenobiotics / Q000378:metabolism*
D018076:DNA, Complementary; D000077297:Pregnane X Receptor; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D011987:Receptors, Steroid; D014157:Transcription Factors; D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; C484320:CYP2U1 protein, human; C585499:Cyp1b1 protein, rat; D065633:Cytochrome P-450 CYP1B1; D000072467:Cytochrome P450 Family 2