Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval, Québec, QC, Canada; Faculté de pharmacie, Université Laval, Québec, QC, Canada.
Centre Nutrition, santé et société (NUTRISS), Institut sur la nutrition et les aliments fonctionnels (INAF), Université Laval, Québec, QC, Canada; École de nutrition, Faculté des sciences de l'agriculture et de l'alimentation, Université Laval, Québec, QC, Canada.
J Lipid Res. 2022 Oct;63(10):100269. doi: 10.1016/j.jlr.2022.100269. Epub 2022 Aug 27.
Low circulating concentrations of insulin-like growth factor binding protein-2 (IGFBP-2) have been associated with dyslipidemia, notably with high triglyceride (TG) levels. However, the determinants by which IGFBP-2 influences lipoprotein metabolism, especially that of TG-rich lipoproteins (TRLs), are poorly understood. Here, we aimed to assess the relationships between IGFBP-2 levels and lipoprotein production and catabolism in human subjects. Fasting IGFBP-2 concentrations were measured in the plasma of 219 men pooled from previous lipoprotein kinetics studies. We analyzed production rate and fractional catabolic rates of TRLapoB-48, and LDL-, IDL-, and VLDLapoB-100 by multicompartmental modeling of l-[5,5,5-D3] leucine enrichment data after a 12 h primed constant infusion in individuals kept in a constant nutritional steady state. Subjects had an average BMI of 30 kg/m, plasma IGFBP-2 levels of 157 ng/ml, and TG of 2.2 mmol/l. After adjustments for age and BMI, IGFBP-2 levels were negatively associated with plasma TG (r = -0.29; P < 0.0001) and positively associated with HDL-cholesterol (r = 0.26; P < 0.0001). In addition, IGFBP-2 levels were positively associated with the fractional catabolic rate of VLDLapoB-100 (r = 0.20; P < 0.01) and IDLapoB-100 (r = 0.19; P < 0.05) and inversely with the production rate of TRLapoB-48 (r = -0.28; P < 0.001). These correlations remained statistically significant after adjustments for age, BMI, and the amount of fat given during the tracer infusion. These findings show that the association between low plasma IGFBP-2 and high TG concentrations could be due to both an impaired clearance of apoB-100-containing VLDL and IDL particles and an increased production of apoB-48-containing chylomicrons. Additional studies are necessary to investigate whether and how IGFBP-2 directly impacts the kinetics of TRL.
循环胰岛素样生长因子结合蛋白-2（IGFBP-2）水平降低与血脂异常有关，特别是与甘油三酯（TG）水平升高有关。然而，IGFBP-2 影响脂蛋白代谢的决定因素，特别是富含甘油三酯的脂蛋白（TRL）的代谢，仍知之甚少。在这里，我们旨在评估 IGFBP-2 水平与人体脂蛋白生成和分解代谢之间的关系。在之前的脂蛋白动力学研究中，我们从 219 名男性的血浆中测量了空腹 IGFBP-2 浓度。我们通过对处于恒定营养稳态的个体进行 12 小时脉冲持续输注 l-[5,5,5-D3]亮氨酸后，利用多房室模型分析了 TRLapoB-48、LDL、IDL 和 VLDLapoB-100 的生成率和分数分解率。研究对象的平均 BMI 为 30kg/m2，IGFBP-2 水平为 157ng/ml，TG 为 2.2mmol/l。在调整年龄和 BMI 后，IGFBP-2 水平与血浆 TG（r=-0.29；P<0.0001）呈负相关，与 HDL-胆固醇（r=0.26；P<0.0001）呈正相关。此外，IGFBP-2 水平与 VLDLapoB-100（r=0.20；P<0.01）和 IDLapoB-100（r=0.19；P<0.05）的分解率呈正相关，与 TRLapoB-48 的生成率呈负相关（r=-0.28；P<0.001）。这些相关性在调整示踪剂输注期间给予的脂肪量后仍然具有统计学意义。这些发现表明，低血浆 IGFBP-2 与高 TG 浓度之间的关联可能是由于 apoB-100 含量的 VLDL 和 IDL 颗粒清除受损以及 apoB-48 含量的乳糜微粒生成增加所致。需要进一步研究以确定 IGFBP-2 是否以及如何直接影响 TRL 的动力学。
