Expression and Induction of Cytochromes P450 in Rat White Adipose Tissue
Expression and Induction of Cytochromes P450 in Rat White Adipose Tissue
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DOI：
10.1124/jpet.104.067066
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发表时间：
2004-10
影响因子：
3.5
通讯作者：
K. Yoshinari;Takeshi Sato;N. Okino;J. Sugatani;M. Miwa
中科院分区：
文献类型：
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作者：
K. Yoshinari;Takeshi Sato;N. Okino;J. Sugatani;M. Miwa
亲脂性环境污染物暴露后往往在脂肪组织中储存。这些化合物在肝脏和肾脏等器官中的细胞毒性以及它们作为内分泌干扰物对生殖组织的异种雌激素作用方面已经得到了很好的研究。然而，这些化学物质对脂肪组织的影响尚未被研究，尽管脂肪组织是分泌肥胖/糖尿病相关激素和细胞因子的重要内分泌组织。在本研究中，我们鉴定了细胞色素P450在大鼠白色脂肪组织中的表达，并研究了典型的亲脂性细胞色素P450诱导性物质，即苯巴比妥、地塞米松和β-萘黄酮的影响。结果表明，β-萘黄酮是脂肪组织和肝脏中较强的CYP1A诱导剂。增加CYP1A1 mRNA、蛋白及其相关活性乙氧基间苯二酚o -去乙基化酶。苯巴比妥和地塞米松也分别诱导脂肪组织中CYP2Bs和CYP3As的mRNA和蛋白表达，但个体间存在显著差异。此外，我们证明了48小时禁食在脂肪组织中与在肝脏中一样有效地诱导CYP2E1 mRNA和蛋白质。这些结果表明，细胞色素P450基因在肝脏中调控的机制在大鼠脂肪组织中也起作用。这提出了在脂肪组织中积累的亲脂性环境污染物可能失调基因表达谱的可能性。
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.