High‐density Lipoprotein Apolipoprotein A‐I Kinetics in Obesity

OBJECTIVE: Low plasma concentrations of high-density lipoprotein (HDL)-cholesterol and apolipoprotein A-I (apoA-I) are independent predictors of coronary artery disease and are often associated with obesity and the metabolic syndrome. However, the underlying kinetic determinants of HDL metabolism are not well understood. RESEARCH METHODS AND PROCEDURES: We pooled data from 13 stable isotope studies to investigate the kinetic determinants of apoA-I concentrations in lean and overweight-obese individuals. We also examined the associations of HDL kinetics with age, sex, BMI, fasting plasma glucose, fasting insulin, Homeostasis Model Assessment score, and concentrations of apoA-I, triglycerides, HDL-cholesterol and low-density lipoprotein-cholesterol. RESULTS: Compared with lean individuals, overweight-obese individuals had significantly higher HDL apoA-I fractional catabolic rate (0.21+/-0.01 vs. 0.33+/-0.01 pools/d; p<0.001) and production rate (PR; 11.3+/-4.4 vs. 15.8+/-2.77 mg/kg per day; p=0.001). In the lean group, HDL apoA-I PR was significantly associated with apoA-I concentration (r=0.455, p=0.004), whereas in the overweight-obese group, both HDL apoA-I fractional catabolic rate (r=-0.396, p=0.050) and HDL apoA-I PR (r=0.399, p=0.048) were significantly associated with apoA-I concentration. After adjustment for fasting insulin or Homeostasis Model Assessment score, HDL apoA-I PR was an independent predictor of apoA-I concentration. DISCUSSION: In overweight-obese subjects, hypercatabolism of apoA-I is paralleled by an increased production of apoA-I, with HDL apoA-I PR being the stronger determinant of apoA-I concentration. This could have therapeutic implications for the management of dyslipidemia in individuals with low plasma HDL-cholesterol.