High‐density lipoprotein apolipoprotein A‐I kinetics: comparison of radioactive and stable isotope studies

Abstract

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.

Effect of obesity on the plasma lipoprotein subclass profile in normoglycemic and normolipidemic men and women

“…Similarly, there is no difference between normotriglyceridemic (plasma TG concentration < 185 mg/dl) men and women in IDL-apoB-100 and LDL-apoB-100 kinetics,62,63 consistent with the absence of sex differences in IDL and LDL subfraction concentrations and LDL subclass distribution and particle size. Studies evaluating HDL-apoA-I and apoA-II kinetics generally report some64–66 or no62,67,68 differences between men and women, indicating relatively small effects on HDL metabolism. Clearly, more kinetic studies are needed to better understand the mechanisms responsible for the observed effects of obesity and sex on plasma lipoprotein profile.…”

Understanding HDL Metabolism and Biology Through In Vivo Tracer Kinetics

“…Additional insights into these labeling techniques have been detailed previously. 50,51 Gas Chromatography Versus Liquid Chromatography-Mass Spectrometry Applied to Endogenous Labeling Mass spectrometry is required to detect stable isotope tracer in proteins. Subjects are usually administered a stable isotope-labeled amino acid (eg, trideuterated leucine [D3-Leu]) by constant infusion or by bolus, which is in turn taken up by tissues and then incorporated into nascent proteins, some of which are secreted into circulation.…”