Submitted on November 13, 2006
Revised on June 1, 2007
Accepted on June 4, 2007
Development of a novel method to determine very low density lipoprotein kinetics
Iqbal A.R. Al-Shayji, Jason M.R. Gill, Josephine Cooney, Samira Siddiqui, and Muriel J. Caslake
Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ
Corresponding Author: j.gill{at}bio.gla.ac.uk
Isotopic tracer methods of determining triglyceride-rich lipoprotein (TRL) kinetics are costly, time-consuming and labour intensive. This study aimed to develop a simpler and cost-effective method of obtaining TRL kinetic data, based on the fact that chylomicrons (CM) compete with large VLDL (VLDL1; Sf 60-400) for the same catalytic pathway. Ten healthy subjects (7 men, fasting triglyceride (TG) 0.5-4.6 mmol.l-1, BMI 21-35 kg.m-2) were given an intravenous infusion of a CM-like TG emulsion (Intralipid) (0.1 g.kg-1 bolus followed by 0.1 g.kg-1.h-1 infusion) for 75-120 minutes to prevent the clearance of VLDL1 by lipoprotein lipase. Multiple blood samples were taken during and post-infusion for separation of Intralipid, VLDL1 and VLDL2 by ultracentrifugation. VLDL1-apolipoprotein B (apoB) and TG production rates were calculated from their linear rises in the VLDL1 fraction during the infusion. Intralipid-TG clearance rate was determined from its exponential decay post-infusion. The production rates of VLDL1-apoB and VLDL1-TG were (mean+/-SEM) 25.4+/-3.9 mg.h-1 and 1076.7+/-224.7 mg.h-1, respectively, and the Intralipid-TG clearance rate was 66.9+/-11.7 pools.d-1. Kinetic data obtained from this method agree with values obtained from stable isotope methods and show the expected relationships with indices of body fatness and insulin resistance (all p<0.05). The protocol is relatively quick, inexpensive, and transferable to non-specialist laboratories.