(OR08-01-23) The Effects of Inflammation-related Stressors, Lutein, and Zeaxanthin on the Structure and Function of High-Density Lipoproteins

Objectives: High-density lipoproteins (HDLs) are key regulators of cellular cholesterol homeostasis and play key roles in preventing the development of several chronic diseases such as cardiovascular disease, renal disease, dementia, and type 2 diabetes. The aim for this project is to measure how various disease-associated modifications, including exposure to Cu²⁺, HOCl, H₂O₂, sialic acid removal, N-glycan removal, high glucose, high fructose, and low pH, and how enrichment of lutein and zeaxanthin affect HDL size distribution and function.

Methods: Modifications to HDLs were performed by incubating with respective compounds at 37 °C for various time (2h, 4h, 18h, 120h, and 192h). Particle size distribution was obtained by analyzing the area of individual particle in electron microscopic images using the software FIJI. HDL functions were measured as cholesterol efflux capacity using the J774 mouse macrophage cell model, and lecithin-cholesterol acyl transferase activity.

Results: Exposure to HOCl (-19.93%, p < 0.05), high glucose (-12.13%, p < 0.005), high fructose (-12.01%, p < 0.05), PNGase F (-8.13%, p < 0.001), and lutein (-6.48, p < 0.01) shifted HDL particle size to smaller median diameter, whereas low pH (+16.23%, p < 0.01)resulted in shifting HDL size to larger diameter. Modifications that resemble inflammatory responses, including low pH (-80.59%, p < 0.001), HOCl (-79.18%, p < 0.001), Cu2+ (-52.36%, p < 0.001), H2O2 (-43.27%, p < 0.01), and high fructose (-23.77%, p < 0.01) significantly reduced the CEC of HDL, whereas zeaxanthin incubation (+18.88%, p < 0.05), lutein incubation (+35.19%, p < 0.01), and neuraminidase treatment (+44.49%, p < 0.001) improved CEC. LCAT activity was also reduced by low pH (-12.07%, p < 0.05), HOCl (-8.86%, p < 0.005), and high fructose (-5.61%, p < 0.05).

Conclusions: Most inflammation-related stressors impaired at least one HDL functional test. Lutein and zeaxanthin individually improved CEC of HDL, but not the LCAT function. Combination of these treatments can provide more information on how lutein and zeaxanthin interact with stressors.

Funding Sources: This research is supported by This project was funded by NIH Grant R01AG062240 and Henry A. Jastro Research Award (2021).