Watts G F, Naoumova R, Cummings M H, Umpleby A M, Slavin B M, Sönksen P H, Thompson G R
Department of Medicine, University of Western Australia, Perth.
Metabolism. 1995 Aug;44(8):1052-7. doi: 10.1016/0026-0495(95)90104-3.
The regulation of apolipoprotein B-100 (apo B) metabolism in man is not fully understood. In vitro studies suggest a key role for the hepatic availability of cholesterol substrate. We therefore examined whether there was a direct association between plasma mevalonic acid (MVA) concentration (an index of in vivo cholesterol synthesis) and hepatic secretion of very-low-density lipoprotein (VLDL) apo B in eight normolipidemic, healthy adult subjects. Hepatic secretion of VLDL apo B was estimated by endogenous labeling of apo B with an 8-hour primed, constant infusion of 1-13C-leucine. Isotopic enrichment of VLDL apo B was measured by gas chromatography-mass spectrometry (GCMS), from which the fractional secretion rate (FSR) was derived by a modified monoexponential function. Plasma concentration of MVA was measured by gas chromatography-electron-capture mass spectrometry in blood samples taken at 9 AM. The absolute secretion rate (ASR) of VLDL apo B (mean +/- SD) was 9.7 +/- 2.6 mg/kg/d, and MVA concentration was 5.0 +/- 2.5 ng/mL. There was a highly significant positive correlation between ASR of VLDL apoB and plasma MVA (r = .88, P = .004), which persisted after adjusting for apo E phenotype. The findings suggest that in vivo cholesterol synthesis is a determinant of hepatic secretion of apo B in normolipidemic subjects.
人类载脂蛋白B-100（apo B）代谢的调节机制尚未完全明确。体外研究表明胆固醇底物的肝脏可利用性起着关键作用。因此，我们在8名血脂正常的健康成年受试者中，研究了血浆甲羟戊酸（MVA）浓度（体内胆固醇合成的一个指标）与极低密度脂蛋白（VLDL）apo B的肝脏分泌之间是否存在直接关联。通过用1-13C-亮氨酸进行8小时的预充、持续输注对内源性apo B进行标记，来估计VLDL apo B的肝脏分泌。通过气相色谱-质谱联用仪（GCMS）测量VLDL apo B的同位素富集情况，并通过修正的单指数函数得出分数分泌率（FSR）。在上午9点采集的血样中，通过气相色谱-电子捕获质谱法测量血浆MVA浓度。VLDL apo B的绝对分泌率（ASR）（均值±标准差）为9.7±2.6 mg/kg/d，MVA浓度为5.0±2.5 ng/mL。VLDL apoB的ASR与血浆MVA之间存在高度显著的正相关（r = 0.88，P = 0.004），在对apo E表型进行校正后该相关性依然存在。这些发现表明，在血脂正常的受试者中，体内胆固醇合成是apo B肝脏分泌的一个决定因素。
