Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.655527
Title: Investigation of total HDL and HDL subclass kinetics using stable isotope techniques in healthy subjects
Author: Wang, Ke
Awarding Body: University of Surrey
Current Institution: University of Surrey
Date of Award: 2015
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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.
Supervisor: Umpleby, Margot; Shojaee- Moradie, Fariba Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.655527  DOI: Not available
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