Context: 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.

Objective: 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.

Setting / paticipants: 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.

Results: 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.

Conclusions: 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.