Associations between insulin-like growth factor binding protein-2 and lipoprotein kinetics in men |
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Institution: | 1. Centre de recherche de l’Institut universitaire de cardiologie et de pneumologie de Québec – Université Laval, Québec, QC, Canada;2. Faculté de pharmacie, Université Laval, Québec, QC, Canada;3. Centre Nutrition, santé et société (NUTRISS), Institut sur la nutrition et les aliments fonctionnels (INAF), Université Laval, Québec, QC, Canada;4. École de nutrition, Faculté des sciences de l’agriculture et de l’alimentation, Université Laval, Québec, QC, Canada;5. Département de médecine, Faculté de médecine, Université Laval, Québec, QC, Canada |
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Abstract: | 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/m2, 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. |
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Keywords: | dyslipidemia IGFBP-2 lipoproteins biomarker tracer clearance production kinetics CRP"} {"#name":"keyword" "$":{"id":"kwrd0020"} "$$":[{"#name":"text" "_":"C-reactive protein FCR"} {"#name":"keyword" "$":{"id":"kwrd0030"} "$$":[{"#name":"text" "_":"fractional catabolic rate IGF"} {"#name":"keyword" "$":{"id":"kwrd0040"} "$$":[{"#name":"text" "_":"insulin-like growth factor IGFBP-2"} {"#name":"keyword" "$":{"id":"kwrd0050"} "$$":[{"#name":"text" "_":"insulin-like growth factor binding protein-2 LPL"} {"#name":"keyword" "$":{"id":"kwrd0060a"} "$$":[{"#name":"text" "_":"lipoprotein lipase PR"} {"#name":"keyword" "$":{"id":"kwrd0060"} "$$":[{"#name":"text" "_":"production rate PS"} {"#name":"keyword" "$":{"id":"kwrd0070"} "$$":[{"#name":"text" "_":"pool size TG"} {"#name":"keyword" "$":{"id":"kwrd0080"} "$$":[{"#name":"text" "_":"triglyceride TRL"} {"#name":"keyword" "$":{"id":"kwrd0090"} "$$":[{"#name":"text" "_":"TG-rich lipoprotein VEGF"} {"#name":"keyword" "$":{"id":"kwrd0090a"} "$$":[{"#name":"text" "_":"vascular endothelial growth factor |
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