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Investigation of total HDL and HDL subclass kinetics using stable isotope techniques in healthy subjects.

Wang, Ke (2015) Investigation of total HDL and HDL subclass kinetics using stable isotope techniques in healthy subjects. Doctoral thesis, University of Surrey.

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Abstract

Background: HDLs are heterogeneous particles, and apoA-I is the major apolipoprotein in human HDL. CVD is a multifactorial condition, and a various lipids and lipoproteins in the plasma are involved in the development of CVD. It has been suggested that HDLs have an inverse association with the risk of CVD. A high sugar intake (especially fructose and sucrose) was found to associate with a low HDL-C level and increased risk of CVD. However, the effect of dietary sugar on HDL kinetics is unclear. An insight of HDL subclass kinetics may provide a better understanding of the whole dynamic of HDL metabolism. Methods: Two studies were undertaken: 1) A controlled, randomized crossover dietary intervention study was carried out in 6 overweight middle-aged men. Subjects underwent two 12-week dietary interventions with high and low non-milk extrinsic sugar diets. Total HDL kinetics was measured using a primed constant intravenous infusion of [1-13C] leucine for 10 hours. 2) A HDL subclass kinetic study was carried out in 6 healthy subjects (3 males and 3 females). An intravenous bolus injection of [1-13C] leucine was applied to measure HDL subclass kinetics. Blood samples were taken during a 10-hour study and the following 2 weeks. Total HDL, HDL2 and HDL3 were separated from the plasma by ultracentrifugation, and αHDL and preβHDL were isolated by agarose gel electrophoresis. ApoA-I in HDL fractions was separated by SDS-PAGE. After purification, hydrolysis and derivatization, the isotopic enrichment of apoA-I in HDL was measured by GC-MS and apoA-I fractional catabolic rate (FCR) and production rate (PR) was calculated for each subclass and total HDL. Results: In the dietary intervention study, the FCR of total HDL apoA-I on the high and low sugar diet (0.20 ± 0.02 and 0.18 ± 0.02 pools/day) was similar, as was the PR (7.33 ± 0.66 and 6.05 ± 0.72 mg/kg/day respectively). In the HDL subclass study, the concentration of αHDL apoA-I (0.97 ± 0.05 g/L) was significantly higher than that of preβHDL apoA-I (0.15 ± 0.03 g/L) (p<0.001). The FCR of αHDL and preβHDL apoA-I was 0.10 ± 0.02 and 0.13 ± 0.04 pools/day, and the PR of αHDL and preβHDL apoA-I was 3.94 ± 0.73 and 0.67 ± 0.12 mg/kg/day respectively. The concentration of HDL3 apoA-I (0.68 ± 0.04 g/L) was significantly higher than that of HDL2 apoA-I (0.23 ± 0.06 g/L) (p=0.002). The FCR of HDL2 and HDL3 apoA-I was 0.15 ± 0.02 pools/day for both, and PR of HDL2 and HDL3 apoA-I was 1.35 ± 0.35 2 and 3.81 ± 0.51 mg/kg/day respectively. A significant difference was observed between αHDL and preβHDL apoA-I PR (p=0.010), and between HDL2 and HDL3 apoA-I PR (p=0.030) in the whole group. The concentration of HDL2 apoA-I was higher in women (0.32 ± 0.08 g/L) than men (0.13 ± 0.02 g/L) though the difference was not significant. HDL2 apoA-I PR was significantly higher in women than men (p=0.017). Conclusion: The high and low sugar diet did not affect HDL metabolism in overweight men. The higher apoA-I concentration of αHDL and HDL3 might be due to the higher apoA-I PR of αHDL and HDL3 compared to preβHDL and HDL2 respectively in healthy subjects. The higher level of HDL2 apoA-I in female than male subjects might be due to the higher PR of HDL2 apoA-I in women.

Item Type: Thesis (Doctoral)
Divisions : Theses
Authors :
AuthorsEmailORCID
Wang, Kewangke.kath@gmail.comUNSPECIFIED
Date : 30 June 2015
Funders : Myself
Contributors :
ContributionNameEmailORCID
Thesis supervisorUmpleby, Margotm.umpleby@surrey.ac.ukUNSPECIFIED
Thesis supervisorShojaee- Moradie, Faribaf.shojaee- moradie@surrey.ac.ukUNSPECIFIED
Depositing User : Ke Wang
Date Deposited : 07 Jul 2015 08:54
Last Modified : 07 Jul 2015 08:54
URI: http://epubs.surrey.ac.uk/id/eprint/807836

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