Effects of Orotic Acid and Di-(2-Ethylhexyl)Phthalate on Microsomal Triglyceride Transfer Protein(MTP) Activity and mRNA Levels in Liver and Intestine of Rats

Orotic acid와 Di-(2-ethylhexyl)phthalate 투여 흰쥐의 간장 및 소장 Microsomal Triglyceride Transfer Protein(MTP) 활성과 mRNA 수준에 미치는 영향

Microsomal triglyceride transfer protein(MTP) activity and mRNA level were investigated in the liver and small intestine of rats fed on di-(2-ethylhexyl)phthalate(DEHP) and orotic acid(OA) as serum triglyceride-reducing agents. The concentration of liver triglyceride was significantly increased in the OA group, but that was not increased in the DEHP group compared with the control group. The concentration of serum triglyceride was significantly decreased in the OA and DEHP groups compared with the control group, but this reduction was more pronounced in the OA group. MTP activity and mRNA level in liver were decreased in the OA group compared with the control group, while MTP activity in the small intestine was increased in the OA group compared with the control group. MTP activities and MTP mRNA levels in both liver and small intestine had no influence by the DEHP dietary feeding, despite the triglyceride-lowering action, compared with the control dietary feeding. The activity of liver microsomal phosphatidate phosphohydrolase(PAP), the rate-limiting enzyme in triglyceride synthesis, was increased in the OA group compared with the control group, but that of cytosolic PAP was decreased in the DEHP group compared with the control group. The result suggest that MTP activity and MTP mRNA level are involved in the triglyceride-lowering action of OA, but those are not involved in that of DEHP.

혈청 중성지질 저하작용을 가지고 있는 것으로 알려진 OA식 및 DEHP식을 각각 투여한 흰쥐의 간장 및 소장에서 MTP 활성과 mRNA 수준을 검토하였다. 간장 중성지질 농도는 대조군에 비교해서 OA군에서 유의하게 증가하였으나, DEHP군에서는 유의한 차이가 없었다. 혈청 중성지질 농도는 대조군에 비해서 OA군 및 DEHP군에서 유의하게 감소하였는데, 이러한 저하는 OA군에서 더욱 현저하였다. 간세포에서의 MTP 활성과 mRNA 수준은 대조군에 비해서 OA군에서 유의하게 저하하였으나, 소장에서의 MTP 활성은 증가하였다. 그러나, 간장 및 소장의 MTP 활성과 mRNA 수준은 대조군과 DEHP군 사이에서는 유의적인 변화가 없었다. 간장에 있어서 중성지질 합성의 중요 조절효소인 microsomal PAP 활성은 대조군에 비해 OA군에서 유의하게 증가하였으나, DEHP군에서는 cytosolic PAP 활성이 감소하였다. 이상의 결과로부터, OA에 의한 혈청 중성지질 저하 작용에는 간장 MTP 활성과 mRNA 유전자 발현이 깊이 관여하였으나, DEHP에 의한 혈청 중성지질 저하 작용에는 MTP 대사와는 무관한 것으로 사료되었다.