II.

II.

OOI, ESTHER M. M., GERALD F. WATTS, MARYAM S. FARVID, DICK C. CHAN, MICHAEL C. ALLEN, SIMON R. ZILKO, AND P. HUGH R. BARRETT. Highdensity lipoprotein apolipoprotein A-I kinetics in obesity. Obes Res. 2005;13:1008 -1016. 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 overweightobese 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, overweightobese individuals had significantly higher HDL apoA-I fractional catabolic rate (0.21 Ϯ 0.01 vs. 0.33 Ϯ 0.01 pools/d; p Ͻ 0.001) and production rate (PR; 11.3 Ϯ 4.4 vs. 15.8 Ϯ 2.77 mg/kg per day; p ϭ 0.001). In the lean group, HDL apoA-I PR was significantly associated with apoA-I concentration (r ϭ 0.455, p ϭ 0.004), whereas in the overweight-obese group, both HDL apoA-I fractional catabolic rate (r ϭ Ϫ0.396, p ϭ 0.050) and HDL apoA-I PR (r ϭ 0.399, p ϭ 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.

To compare the kinetic determinants of high-density lipoprotein (HDL) apolipoprotein A-I (apoA-I) concentration in lean normolipidaemic subjects using radioisotope and stable isotope studies. We pooled data from 16 radioisotope and 13 stable isotope studies to investigate the kinetics of apoA-I in lean normolipidemic individuals. We also examined the associations of HDL kinetic parameters with age, sex, body mass index (BMI) and concentrations of apoA-I, triglycerides, HDL cholesterol and low-density lipoprotein (LDL) cholesterol. Lean subjects from radioisotope and stable isotope studies were matched for age, gender, BMI and lipid profile. The apoA-I concentration was significantly lower in the radioisotope group than the stable isotope group (P = 0.031). There was no significant difference in HDL apoA-I fractional catabolic rate (FCR) and production rate (PR) between the groups. In the radioisotope group, HDL apoA-I FCR was significantly associated with apoA-I and HDL cholesterol concentrations (r = -0.681, P < 0.001 and r = -0.542, P < 0.001, respectively), whereas in the stable isotope group, only HDL apoA-I PR was significantly associated with apoA-I concentration (r = 0.455, P = 0.004). Our findings suggest that HDL apoA-I FCR is the primary determinant of apoA-I concentrations in lean subjects in studies using radiotracer techniques. By contrast, HDL apoA-I PR is the primary determinant of apoA-I concentration in lean subject in studies employing stable isotope methods. These discrepancies may be reconciled by differences in methodologies and/or study population characteristics.