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 of men and women with 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 ∼30% of the variance in VLDL-TG SR; 3) ∼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 × race interaction) of VLDL-TG SR. CONCLUSIONS: The regulation of plasma VLDL-TG concentration is complex and influenced by multiple metabolic factors. Many people with obesity have normal plasma VLDL-TG concentrations and kinetics, whereas those with high plasma VLDL-TG concentrations have increased VLDL-TG SR and other markers of cardiometabolic disease risk.