Expression and Induction of Cytochromes P450 in Rat White Adipose Tissue

Kouichi Yoshinari; Takeshi Sato; Nao Okino; Junko Sugatani; Masao Miwa

doi:10.1124/jpet.104.067066

Abstract

Lipophilic environmental pollutants are often stored in adipose tissues after exposure. These compounds have been well studied in terms of their cell toxicity in organs such as liver and kidney, and their xenoestrogenic action on reproductive tissues as endocrine disruptors. However, the effects of these chemicals on the depot, adipose tissue, have not been studied, although adipose tissue is an important endocrine tissue secreting obesity/diabetes-related hormones and cytokines. In this study, we identified the expression of cytochromes P450 in rat white adipose tissues and investigated the effects of typical lipophilic cytochrome P450 inducers, namely phenobarbital, dexamethasone, and β-naphthoflavone. The results showed that β-naphthoflavone was a strong CYP1A inducer in adipose tissue as well as in liver. It increased CYP1A1 mRNA, protein, and its related activity, ethoxyresorufin O-deethylase. Phenobarbital and dexamethasone also induced both the mRNA and protein of CYP2Bs and CYP3As, respectively, in adipose tissue, although significant interindividual differences were observed. Furthermore, we demonstrated that 48 h of fasting was as effective in adipose tissue as in the liver in the induction of CYP2E1 mRNA and protein. These results suggest that the mechanisms by which cytochrome P450 genes are regulated in the liver are also functional in rat adipose tissues. This has raised the possibility that lipophilic environmental contaminants accumulated in adipose tissue may dysregulate the gene expression profile.

Footnotes

This work was supported in part by a grant-in-aid for Encouragement of Young Scientists and The 21st Century COE Program from the Ministry of Education, Culture, Sports, Science and Technology and by the Goto Research Grant from University of Shizuoka.
doi:10.1124/jpet.104.067066.
ABBREVIATIONS: P450, cytochrome P450; AHR, aryl hydrocarbon receptor; PB, phenobarbital; DEX, dexamethasone; CAR, constitutive androstane receptor; PXR, pregnane X receptor; ARNT, AHR nuclear translocator; PCB, polychlorinated biphenyl; DDT, 1,1,1-trichloro-2,2-bis-(p-chlorophenyl)ethane; DDE, 1,1-dichloro-2,2-bis-(p-chlorophenyl)ethylene; BNF, β-naphthoflavone (5,6-benzoflavone); OR, NADPH cytochrome P450 reductase; RT-PCR, reverse transcription-polymerase chain reaction; RPS9, ribosomal protein S9; EROD, ethoxyresorufin O-deethylase; RXR, retinoid X receptor α.
- Received February 17, 2004.
- Accepted May 18, 2004.