Bach-Ngohou K, Ouguerram K, Nazih H, Maugère P, Ripolles-Piquer B, Zaïr Y, Frénais R, Krempf M, Bard J M
INSERM U539, Centre de recherche en Nutrition Humaine, CHU Hotel-Dieu, Nantes, France.
Int J Obes Relat Metab Disord. 2002 Nov;26(11):1451-8. doi: 10.1038/sj.ijo.0802149.
Insulin resistance related to obesity and diabetes is characterized by an increase in plasma TG-rich lipoprotein concentrations. Apolipoprotein (apo) E plays a crucial role in the metabolism of these lipoproteins and particularly in the hepatic clearance of their remnants. The aim of this study was to explore apoE kinetics of obese subjects and to determine what parameters could influence its metabolism.
Using stable-isotope labelling technique ([(2)H(3)]-leucine-primed constant infusion) and monocompartmental model (SAAM II computer software), we have studied the plasma kinetics of very-low-density lipoprotein (VLDL) and high-density lipoprotein (HDL) apoE in 12 obese subjects (body mass index (BMI) 27.4-36.6 kg/m(2)): Seven were type 2 diabetics (age 47-65 y; HbA1c 7.1-10.2%) and five were non-diabetics (age 40-51 y, HbA1c: 4.9-5.3%). Six of the diabetic subjects were insulin resistant as assessed by insulin sensitivity index (HOMA 2.6-10.0), while non-diabetic subjects were all insulin sensitive (HOMA 1.2-2.1).
Plasma VLDL and HDL apoE concentrations were significantly higher in diabetic than in non-diabetic subjects (5.74+/-1.60 vs 1.46+/-1.74 mg/l, P<0.01 and 17.81+/-6.67 vs 9.97+/-3.32 mg/l, P<0.05). These increased levels were associated with significantly higher absolute production rate (APR) of VLDL and HDL apoE (0.714+/-0.343 vs 0.130+/-0.200 mg/kg/day, P<0.01, and 0.197+/-0.087 vs 0.080+/-0.060 mg/kg/day, P<0.05, respectively) while no significant difference was found for fractional catabolic rate (FCR) of VLDL and HDL apoE (3.44+/-1.64 vs 1.97+/-0.84/day and 0.30+/-0.12 vs 0.19+/-0.09/day, respectively). In the whole population, BMI was not correlated with any of apoE kinetic data. HOMA was positively correlated with FCR of VLDL apoE (r=0.64, P<0.05) and tended to be correlated with APR of VLDL apoE (r=0.58, P=0.06). HbA1c was positively correlated with APR and FCR of both VLDL apoE (r=0.91 and 0.78, P<0.01, respectively) and HDL apoE (r=0.66 and 0.69, P<0.05, respectively).
Obese diabetics are characterized by elevated VLDL and HDL apoE levels associated with enhancement of VLDL and HDL apoE production rates. Whereas obesity did not influence apoE kinetic parameters in itself, insulin resistance may lead to an increase in VLDL apoE production and fractional catabolic rates. Diabetes and the glycemic control may also specifically influence the kinetics of both VLDL and HDL apoE. All together, these disorders should explain at least part of the increase in VLDL and HDL apoE observed in diabetes.
与肥胖和糖尿病相关的胰岛素抵抗的特征是富含甘油三酯的血浆脂蛋白浓度升高。载脂蛋白（apo）E在这些脂蛋白的代谢中起关键作用，尤其是在其残粒的肝脏清除中。本研究的目的是探讨肥胖受试者的载脂蛋白E动力学，并确定哪些参数会影响其代谢。
我们使用稳定同位素标记技术（[（2）H（3）]-亮氨酸预充恒速输注）和单室模型（SAAM II计算机软件），研究了12名肥胖受试者（体重指数（BMI）27.4-36.6 kg/m²）中极低密度脂蛋白（VLDL）和高密度脂蛋白（HDL）载脂蛋白E的血浆动力学：7名是2型糖尿病患者（年龄47-65岁；糖化血红蛋白（HbA1c）7.1-10.2%），5名是非糖尿病患者（年龄40-51岁，HbA1c：4.9-5.3%）。通过胰岛素敏感性指数评估，6名糖尿病受试者存在胰岛素抵抗（胰岛素抵抗指数（HOMA）2.6-10.0），而非糖尿病受试者均为胰岛素敏感（HOMA 1.2-2.1）。
糖尿病患者的血浆VLDL和HDL载脂蛋白E浓度显著高于非糖尿病患者（5.74±1.60 vs 1.46±1.74 mg/l，P<0.01；17.81±6.67 vs 9.97±3.32 mg/l，P<0.05）。这些升高的水平与VLDL和HDL载脂蛋白E的绝对生成率（APR）显著升高相关（分别为0.714±0.343 vs 0.130±0.200 mg/kg/天，P<0.01；0.197±0.087 vs 0.080±0.060 mg/kg/天，P<0.05），而VLDL和HDL载脂蛋白E的分解代谢率（FCR）无显著差异（分别为3.44±1.64 vs 1.97±0.84/天；0.30±0.12 vs 0.19±0.09/天）。在整个人群中，BMI与任何载脂蛋白E动力学数据均无相关性。HOMA与VLDL载脂蛋白E的FCR呈正相关（r=0.64，P<0.05），并倾向于与VLDL载脂蛋白E的APR相关（r=0.58，P=0.06）。HbA1c与VLDL载脂蛋白E和HDL载脂蛋白E的APR及FCR均呈正相关（分别为r=0.91和0.78，P<0.01；r=0.66和0.69，P<0.05）。
肥胖糖尿病患者的特征是VLDL和HDL载脂蛋白E水平升高，同时伴有VLDL和HDL载脂蛋白E生成率增加。虽然肥胖本身不影响载脂蛋白E动力学参数，但胰岛素抵抗可能导致VLDL载脂蛋白E生成和分解代谢率增加。糖尿病和血糖控制也可能特异性地影响VLDL和HDL载脂蛋白E的动力学。总之，这些紊乱至少应能解释糖尿病中观察到的VLDL和HDL载脂蛋白E升高的部分原因。
