Glatz J F, Turner P R, Katan M B, Stalenhoef A F, Lewis B
Department of Human Nutrition, Agricultural University, Wageningen, The Netherlands.
Ann N Y Acad Sci. 1993 Mar 15;676:163-79. doi: 10.1111/j.1749-6632.1993.tb38732.x.
Serum cholesterol in man rises when cholesterol intake increases, but the extent of the elevation varies between subjects. Part of the variation between subjects is spurious and not reproducible; it is caused by random diet-independent fluctuations of serum lipid levels. Part is due to consistent metabolic differences between subjects. We have earlier found that responsiveness was associated with higher initial total and HDL cholesterol, lower habitual cholesterol consumption, and lower body mass index, and unrelated to gender, age, or apo E phenotype. We have now investigated the metabolic basis of variability by measuring turnover rates of low density lipoprotein (LDL) apolipoprotein B (apo B) on a low-cholesterol diet (140 mg/day) and a high-cholesterol diet (900 mg/day) in 8 volunteers with well-defined differences in the responsiveness of their serum cholesterol to diet. Autologous 125I-LDL was injected on day 23 of each diet period. Its fractional catabolic rate (FCR) was estimated from the ratio of 125I in urine over that in plasma, seven days after injection. FCR (mean +/- SD) increased from 0.24 +/- 0.02 pools/day on the low- to 0.31 +/- 0.20 on the high-cholesterol diet. LDL-apo B concentration rose from 49 +/- 13 to 63 +/- 12 mg/dl, and LDL-apo B production rate, calculated as FCR x concentration/body weight, from 4.8 +/- 1.2 to 8.0 +/- 1.4 mg/kg/day. The individual rise in production rate was significantly correlated with the rise in the serum concentration of LDL-apo B (r = 0.90) or LDL-cholesterol (r = 0.75), and also with the rise in total serum cholesterol measured in these same subjects in similar experiments 3-4 years earlier (r = 0.74). Degradation of LDL by freshly isolated blood mononuclear cells and by mononuclear cells incubated for 72 h in lipoprotein-deficient medium (derepressed cells) was measured on both diets in these and in additional volunteers. The rate of degradation (mean +/- SD) of standard human LDL by fresh cells was 336 +/- 166 ng LDL protein/mg cell protein per 8 h on the low-cholesterol diet, and decreased by 147 +/- 180 ng/mg per 8 h or 44% on the high-cholesterol diet (n = 23, p < 0.01). The catabolic activity of derepressed cells obtained when subjects were on the low-cholesterol diet was negatively related to the LDL cholesterol response (r = -0.57, n = 18, p < 0.05), and to the total cholesterol response in earlier experiments (r = -0.45, n = 18, p < 0.10).(ABSTRACT TRUNCATED AT 400 WORDS)
人体血清胆固醇会随着胆固醇摄入量的增加而升高，但升高的程度在个体之间存在差异。个体间的部分差异是虚假的且不可重复；这是由血清脂质水平与饮食无关的随机波动引起的。部分差异是由于个体间持续存在的代谢差异。我们之前发现，反应性与较高的初始总胆固醇和高密度脂蛋白胆固醇水平、较低的习惯性胆固醇摄入量以及较低的体重指数相关，与性别、年龄或载脂蛋白E表型无关。我们现在通过测量8名志愿者在低胆固醇饮食（140毫克/天）和高胆固醇饮食（900毫克/天）下低密度脂蛋白（LDL）载脂蛋白B（apo B）的周转率，来研究这种变异性的代谢基础。这些志愿者血清胆固醇对饮食的反应性差异明确。在每个饮食阶段的第23天注射自体125I-LDL。注射7天后，根据尿中125I与血浆中125I的比值估算其分数分解代谢率（FCR）。FCR（平均值±标准差）从低胆固醇饮食时的0.24±0.02池/天增加到高胆固醇饮食时的0.31±0.20池/天。LDL-apo B浓度从49±13毫克/分升升至63±12毫克/分升，LDL-apo B产生率（计算为FCR×浓度/体重）从4.8±1.2毫克/千克/天增至8.0±1.4毫克/千克/天。产生率的个体升高与LDL-apo B血清浓度的升高（r = 0.90）或LDL-胆固醇的升高（r = 0.75）显著相关，也与这些受试者在3 - 4年前类似实验中测得的总血清胆固醇升高相关（r = 0.74）。在这些志愿者以及其他志愿者中，在两种饮食条件下都测量了新鲜分离的血液单核细胞以及在脂蛋白缺乏培养基中孵育72小时的单核细胞（去抑制细胞）对LDL的降解情况。新鲜细胞对标准人LDL的降解率（平均值±标准差）在低胆固醇饮食时为每8小时336±166纳克LDL蛋白/毫克细胞蛋白，在高胆固醇饮食时每8小时降低147±180纳克/毫克，即降低44%（n = 23，p < 0.01）。受试者处于低胆固醇饮食时获得的去抑制细胞的分解代谢活性与LDL胆固醇反应呈负相关（r = -0.57，n = 18，p < 0.05），与早期实验中的总胆固醇反应呈负相关（r = -0.45，n = 18，p < 0.10）。（摘要截断于400字）
