Abstract

Very low-density lipoproteins (VLDL) are a major risk factor for cardiovascular disease. The concentrations of VLDL particles and VLDL-triglyceride (TG) in plasma are lower in women than men, but the mechanisms responsible for these differences are unclear. The objective of the study was to investigate the effects of sex on VLDL-TG and VLDL-apolipoprotein B-100 (apoB-100) metabolism. EXPERIMENTAL DESIGN AND MAIN OUTCOME MEASURES: We measured basal VLDL-TG and VLDL-apoB-100 kinetics by using stable isotope labeled tracers. Twenty-six healthy, lean subjects (13 men, aged 29+/-5 yr; 13 women, aged 28+/-6 yr) were studied in the General Clinical Research Center at Washington University School of Medicine. VLDL-TG and VLDL-apoB-100 concentrations were less in women than men (P<0.05). The secretion rate of VLDL-TG was approximately 70% greater (P<0.05), whereas the secretion rate of VLDL-apoB-100 (i.e. VLDL particles) was approximately 20% less (P<0.05) in women than men. The molar ratio of VLDL-TG and VLDL-apoB-100 secretion rates was therefore more than double (P<0.05) in women than men. VLDL-TG plasma clearance rate was approximately 70% greater in women than men (P<0.05), whereas VLDL-apoB-100 plasma clearance rate was not different between sexes. However, VLDL-TG and VLDL-apoB-100 mean residence times in plasma were both shorter (by 45 and 25%, respectively; P<0.05) in women than men. Increased VLDL-TG plasma clearance is responsible for lower VLDL-TG concentration, whereas decreased VLDL-apoB-100 secretion rate, combined with shorter VLDL-apoB-100 residence time in plasma, is responsible for lower VLDL-apoB-100 concentration in women than men. The greater molar ratio of VLDL-TG and VLDL-apoB-100 secretion rates suggests that the liver in women secretes fewer but TG-richer VLDL particles than the liver in men.

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