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Study on the regulation of ketone body metabolism in the action of endocrine disrupting chemicals

内分泌干扰物作用下酮体代谢调节研究

基本信息

批准号：
18590122
负责人：
FUKUI Tetsuya
金额：
$ 2.49万
依托单位：
Hoshi University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

项目摘要

Acetoacetyl-CoA synthetase(AACS, EC 6.2.1.16) is a novel ketone body-utilizing enzyme, which activates acetoacetic acid to its CoA ester for the synthesis of fatty acid and cholesterol. Since expression of this enzyme is sensitive to endocrine disrupting chemical, bisphenol, and is sex-dependent especially remarkable in adipose tissue, we examined effects of castration on AACS mRNA expression in rat white adipose tissue(WAT) in order to elucidate how AACS is involved in sex-dependent metabolic differences in adipose tissues. As a result, castration did not affect any changes in the level of serum ketone bodies, but it significantly decreased AACS gene expression in subcutaneous WAT. In contrast, expression of the other ketone body utilizing enzyme, succinyl-CoA : 3-oxoacid CoA-transferase(SCOT), did not change. Next, in order to investigate regulatory factors of AACS gene expression in male WAT, we examined the effects of a male hormone on AACS gene expression using mouse adult primiti … More ve mesenchymal ST-13 preadipocytes. After testosterone treatment, AACS mRNA expression was increased in MIX-induced adipocytes. However, in non-induced cells, such an increase was not observed. By high fat diet(HFD) feeding, AACS mRNA expression in subcutaneous WAT was increased 〜1.49-fold. However, such increase was not observed in mesenteric WAT. ACC-1 mRNA expression was slightly decreased in subcutaneous WAT, and significantly decreased in mesenteric WAT by HFD feeding. ACC-2 mRNA expression in subcutaneous WAT was increased, while it was not detected in mesenteric WAT. Since AACS could play an important role in the utilization of ketone body for the fatty acid synthesis in the cytosol of mature adipocytes, our data suggest that AACS plays an important role on regional-specific ketone body-incorporation into the subcutaneous adipocytes under hypernutritional condition. Moreover, the subcutaneous WAT might play a regulatory role for the control of ketone body concentration in circulating blood. Less

乙酰乙酰辅酶A合成酶（AACS，EC 6.2.1.16）是一种新型酮体利用酶，可将乙酰乙酸活化为其辅酶A酯，用于合成脂肪酸和胆固醇。由于该酶的表达对内分泌干扰化学物质双酚敏感，并且具有性别依赖性，在脂肪组织中尤其显着，因此我们研究了去势对大鼠白色脂肪组织（WAT）中 AACS mRNA 表达的影响，以阐明 AACS 如何参与脂肪组织中性别依赖性代谢差异。结果，去势并没有影响血清酮体水平的任何变化，但它显着降低了皮下WAT中AACS基因的表达。相反，另一种酮体利用酶琥珀酰辅酶A：3-含氧酸辅酶A转移酶(SCOT)的表达没有变化。接下来，为了研究雄性 WAT 中 AACS 基因表达的调节因素，我们使用小鼠成年原发性 ve 间充质 ST-13 前脂肪细胞检查了雄性激素对 AACS 基因表达的影响。睾酮治疗后，MIX 诱导的脂肪细胞中 AACS mRNA 表达增加。然而，在非诱导细胞中，没有观察到这种增加。通过高脂饮食（HFD）喂养，皮下WAT中的AACS mRNA表达增加〜1.49倍。然而，在肠系膜 WAT 中未观察到这种增加。通过 HFD 喂养，皮下 WAT 中 ACC-1 mRNA 表达略有下降，肠系膜 WAT 中 ACC-1 mRNA 表达显着下降。皮下WAT中ACC-2 mRNA表达增加，而肠系膜WAT中未检测到。由于AACS在利用酮体合成成熟脂肪细胞胞质中的脂肪酸方面发挥着重要作用，因此我们的数据表明，AACS在高营养条件下区域特异性酮体掺入皮下脂肪细胞中发挥着重要作用。此外，皮下WAT可能对循环血液中酮体浓度的控制发挥调节作用。较少的