Kinetic and Related Determinants of Plasma Triglyceride Concentration in Abdominal Obesity: Multicenter Tracer Kinetic Study

Abstract

<p><i><b>Objectives</b></i> - Patients with obesity and diabetes mellitus have increased risk of cardiovascular disease. A major cause is an atherogenic dyslipidemia related primarily to elevated plasma concentrations of triglyceride-rich lipoproteins. The aim of this study was to clarify determinants of plasma triglyceride concentration. We focused on factors that predict the kinetics of very-low density lipoprotein 1 (VLDL₁) triglycerides.<br/> <i><b>Approach and Results</b></i> - A multicenter study using dual stable isotopes (deuterated leucine and glycerol) and multicompartmental modeling was performed to elucidate the kinetics of triglycerides and apoB in VLDL₁ in 46 subjects with abdominal obesity and additional cardiometabolic risk factors. Results showed that plasma triglyceride concentrations were dependent on both the secretion rate (<i>r</i>=0.44, <i>P</i><0.01; <i>r</i>=0.45, <i>P</i><0.01) and fractional catabolism (<i>r</i>=0.49, <i>P</i><0.001;<i> r</i>=0.55, <i>P</i><0.001) of VLDL₁-triglycerides and VLDL₁-apoB. Liver fat mass was independently and directly associated with secretion rates of VLDL₁-triglycerides (<i>r</i>=0.56, <i>P</i><0.001) and VLDL₁-apoB (<i>r</i>=0.53, <i>P</i><0.001). Plasma apoC-III concentration was independently and inversely associated with the fractional catabolisms of VLDL₁-triglycerides (<i>r</i>=0.48, <i>P</i><0.001) and VLDL₁-apoB (<i>r</i>=0.51, <i>P</i><0.001).<br/> <i><b>Conclusions</b></i> - Plasma triglyceride concentrations in abdominal obesity are determined by the kinetics of VLDL₁ subspecies, catabolism being mainly dependent on apoC-III concentration and secretion on liver fat content. Reduction in liver fat and targeting apoC-III may be an effective approach for correcting triglyceride metabolism atherogenic dyslipidemia in obesity.</p>