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Updated: May 18, 2026

High-Density Lipoprotein-Specific Phospholipid Efflux Assay
Published on: September 30, 2025
High density lipoprotein is an inappropriate substrate for hepatic lipase in postmenopausal women
Valeria Zago1, Verónica Miksztowicz, Leonardo Cacciagiú
1Laboratory of Lipids and Lipoproteins, Department of Clinical Biochemistry, Faculty of Pharmacy and Biochemistry, INFIBIOC, University of Buenos Aires, Argentina. vzago@ffyb.uba.ar
Insights
Postmenopausal women have triglyceride-enriched HDL, making it a poor substrate for hepatic lipase (HL). This suggests reduced antiatherogenic function despite normal HDL levels, impacting cardiovascular risk.
Area of Science:
- Lipid metabolism
- Cardiovascular disease research
- Menopause studies
Background:
- High-density lipoprotein (HDL) plays a crucial role in antiatherogenic effects, influenced by both concentration and quality.
- Hepatic lipase (HL) modifies HDL during reverse cholesterol transport.
- Cardiovascular risk elevates post-menopause, yet HDL levels remain stable despite increased HL.
Purpose of the Study:
- To evaluate HDL's capacity as a substrate for HL in healthy postmenopausal women (PMW).
- To compare HDL substrate quality between PMW and premenopausal women (PreMW).
Main Methods:
- Studied 20 PMW (51-60 years) and 20 PreMW (26-40 years).
- Assessed fasting serum lipid-lipoprotein profile and HDL composition.
- Incubated increasing HDL-triglyceride concentrations with HL from post-heparin plasma and measured kinetic parameters (Km(app), Vmax).
Main Results:
- HDL from PMW showed significant triglyceride enrichment compared to PreMW (p<0.001).
- Kinetic analysis revealed higher apparent Michaelis constant (Km(app)) in PMW (p<0.0001), directly correlating with HDL triglycerides.
- Catalytic efficiency (Vmax/Km(app)) was reduced in PMW compared to controls (p=0.0001).
Conclusions:
- Triglyceride-rich HDL in PMW is a poor substrate for HL.
- This impaired substrate quality suggests that HDL may not effectively perform its antiatherogenic function in PMW.
- Reduced HDL quality, not just concentration, may contribute to increased cardiovascular risk post-menopause.
Background:
HDL antiatherogenic effects would not only depend on its concentration but also on its biological quality. Hepatic lipase (HL) action on HDL acts in one of the last steps of reverse cholesterol transport. Cardiovascular risk increases after menopause, however HDL does not decrease even when HL is increased. We evaluated HDL capacity as a substrate of HL in healthy postmenopausal women (PMW).
Methods:
We studied 20 PMW (51-60 y) and 20 premenopausal (PreMW) (26-40 y). In fasting serum, lipid-lipoprotein profile and HDL composition were assessed. Optimal assay conditions for HDL/HL ex vivo incubation were established. Increasing HDL-triglyceride concentrations (0.015 to 0.20 mmol/l) were incubated with post-heparin plasma obtained from a single healthy donor as a source of HL. Free fatty acids were measured and kinetic parameters calculated: K(m)(app), inverse to enzyme affinity, and V(max).
Results:
HDL composition in PMW exhibits triglyceride enrichment (p<0.001). Kinetic analysis revealed higher K(m)(app) in PMW [130 (40-380) vs 45 (20-91) mmol/l, p<0.0001)] correlating directly with HDL-triglycerides (r=0.7, p=0.0001). Catalytic efficiency, V(max)/K(m)(app) was reduced when compared to controls (p=0.0001).
Conclusion:
Triglyceride-enriched HDL from PMW constitutes a poor substrate for HL suggesting that this particle may not exert efficiently its antiatherogenic function, regardless of plasma concentration.
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