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

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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