Riches F M, Watts G F, Naoumova R P, Kelly J M, Croft K D, Thompson G R
University Department of Medicine and West Australia Heart Research Institute, University of Western Australia, Royal Perth Hospital.
Int J Obes Relat Metab Disord. 1998 May;22(5):414-23. doi: 10.1038/sj.ijo.0800602.
To test the hypothesis that the hepatic secretion of very-low-density lipoprotein (VLDL) apolipoprotein B-100 (apoB) is increased in men with visceral obesity and to examine whether the oversecretion of this apolipoprotein is related to insulin resistance and increased hepatic availability of lipid substrates.
16 obese men (body mass index (BMI) > 30 kg/m2, waist circumference > 100 cm) and 16 non-obese, age matched men, were studied.
The hepatic secretion of VLDL apoB was measured using a primed (1 mg/kg), constant (1 mg/kg/h), intravenous infusion of 1-[13C]-leucine. Isotopic enrichment of VLDL apoB was determined using gas-chromatography mass spectrometry and a multi-compartmental model (SAAM-II) was used to estimate the fractional turnover rate of VLDL apoB.
Plasma concentrations of total cholesterol, triglyceride, glucose, insulin, mevalonic acid and lathosterol, as well as dietary fat intake, were significantly higher (P < 0.05) in obese than control subjects. The obese subjects had significantly lower high-density-lipoprotein cholesterol (P < 0.01). VLDL apoB pool size and hepatic secretion rate (mg/kg fat free mass/d) were significantly higher in the obese than non-obese subjects (P < 0.02). The fractional catabolic rate of VLDL apoB was lower in the obese subjects compared with controls, but the difference did not attain conventional significance (P=0.053). In pooled analysis, there was a significant positive association (P < 0.05) between VLDL apoB secretion rate (mg/kg fat free mass/d) and waist-to-hip ratio (WHR), waist circumference, and fasting plasma triglyceride, insulin and glucose concentrations. In multiple linear regression analysis, the association between VLDL apoB secretion and fasting insulin concentration was independent of age, apolipoprotein E (apoE) genotype, mevalonic acid concentration, free fatty acid concentration and fat intake.
Our findings are consistent with the hypothesis that in visceral obesity, insulin resistance and the associated increased lipid substrate supply to the liver contribute to hepatic oversecretion of apoB; expansion in the VLDL apoB pool size may also be due to a catabolic defect related to insulin resistance.
验证内脏型肥胖男性极低密度脂蛋白（VLDL）载脂蛋白B-100（apoB）肝脏分泌增加的假说，并研究该载脂蛋白分泌过多是否与胰岛素抵抗以及肝脏脂质底物供应增加有关。
研究了16名肥胖男性（体重指数（BMI）>30 kg/m²，腰围>100 cm）和16名年龄匹配的非肥胖男性。
采用初量（1 mg/kg）、恒速（1 mg/kg/h）静脉输注1-[¹³C]-亮氨酸的方法测量VLDL apoB的肝脏分泌。使用气相色谱-质谱法测定VLDL apoB的同位素富集情况，并采用多室模型（SAAM-II）估算VLDL apoB的分数转换率。
肥胖受试者的总胆固醇、甘油三酯、葡萄糖、胰岛素、甲羟戊酸和羊毛甾醇的血浆浓度以及膳食脂肪摄入量均显著高于对照组（P<0.05）。肥胖受试者的高密度脂蛋白胆固醇显著降低（P<0.01）。肥胖受试者的VLDL apoB池大小和肝脏分泌率（mg/kg去脂体重/天）显著高于非肥胖受试者（P<0.02）。与对照组相比，肥胖受试者中VLDL apoB的分解代谢率较低，但差异未达到传统意义（P=0.053）。在汇总分析中，VLDL apoB分泌率（mg/kg去脂体重/天）与腰臀比（WHR）、腰围以及空腹血浆甘油三酯、胰岛素和葡萄糖浓度之间存在显著正相关（P<0.05）。在多元线性回归分析中，VLDL apoB分泌与空腹胰岛素浓度之间的关联独立于年龄、载脂蛋白E（apoE）基因型、甲羟戊酸浓度、游离脂肪酸浓度和脂肪摄入量。
我们的研究结果与以下假说一致，即在内脏型肥胖中，胰岛素抵抗以及肝脏脂质底物供应增加导致apoB肝脏分泌过多；VLDL apoB池大小的扩大也可能归因于与胰岛素抵抗相关的分解代谢缺陷。
