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

乙酰乙酰辅酶a合成酶（Acetoacetyl-CoA synthetase, EC 6.2.1.16）是一种新型的酮体利用酶，它将乙酰乙酸活化为辅酶a酯，用于脂肪酸和胆固醇的合成。由于该酶的表达对内分泌干扰化学物质双酚敏感，并且在脂肪组织中具有性别依赖性，因此我们研究了阉割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的代谢差异。结果表明，去势不影响血清酮体水平的变化，但显著降低了皮下WAT中AACS基因的表达。相比之下，另一个酮体利用酶琥珀酰辅酶a: 3-氧酸辅酶a转移酶（SCOT）的表达没有变化。接下来，为了研究AACS基因在雄性WAT中表达的调控因素，我们利用小鼠成年原始间充质ST-13前脂肪细胞检测了一种雄性激素对AACS基因表达的影响。睾酮治疗后，混合液诱导的脂肪细胞中AACS mRNA表达增加。然而，在非诱导细胞中，没有观察到这种增加。高脂饲料（HFD）饲喂后，皮下WAT中AACS mRNA的表达量增加了1.49倍。然而，在肠系膜WAT中没有观察到这种增加。ACC-1 mRNA的表达在皮下WAT中略有降低，在肠系膜WAT中显著降低。ACC-2 mRNA在皮下WAT中表达升高，而在肠系膜WAT中未见表达。由于AACS在成熟脂肪细胞胞浆中利用酮体合成脂肪酸中发挥了重要作用，我们的数据表明，在高营养条件下，AACS在皮下脂肪细胞的区域特异性酮体结合中发挥了重要作用。此外，皮下WAT可能对控制循环血液中酮体浓度起调节作用。少

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