VLDL Triglyceride Kinetics in Lean, Overweight, and Obese Men and Women

Context: High-plasma very low-density lipoprotein (VLDL) triglyceride (TG) concentration and alterations in VLDL-TG metabolism are associated with cardiometabolic disease. Objective: This study sought to evaluate the interrelationships among factors purported to regulate VLDL-TG metabolism in a large cohort ofmenandwomenwith a wide range in body adiposity and fat distribution but without diabetes. Subjects and Design: We assessed body composition and fat distribution, plasma insulin concentration, free fatty acid availability, and basal VLDL-TG and VLDL-apoB-100 (VLDL particle number) kinetics in 233 lean, overweight, and obese men and women. Results: We found that: 1) plasma VLDL-TG concentration is determined primarily by VLDL-TG secretion rate (SR) in men and by VLDL-TG clearance rate in women; 2) there is a dissociation between VLDL-TG and VLDL-apoB-100 SRs, and VLDL-apoB-100 SR only explains similar to 30% of the variance in VLDL-TG SR; 3) similar to 50% of people with obesity have high plasma VLDL-TG concentration due to both an increased VLDL-TG SR and a decreased rate of VLDL-TG plasma clearance, and they have lower plasma high-density lipoprotein-cholesterol concentration and more intra-abdominal and liver fat than those with normal VLDL-TG concentration; and 4) fat-free mass, liver fat content and the rate of free fatty acid release into plasma are independent predictors (with a sex x race interaction) of VLDL-TG SR. Conclusions: The regulation of plasma VLDL-TG concentration is complex and influenced by multiple metabolic factors. Manypeople with obesity have normal plasmaVLDL-TGconcentrationsand kinetics, whereas those with high plasma VLDL-TG concentrations have increased VLDL-TG SR and other markers of cardiometabolic disease risk.