Dysregulation of lipid metabolism is implicated in diabetes mellitus and cardiovascular disease. High-density lipoproteins (HDL), which remove excess cholesterol from cells, form a heterogeneous population of mature spherical and nascent discoidal particles 8-12 nm in diameter. Mature HDL contains a core of apolar lipids (cholesterol esters, triacylglycerol) and a surface of polar lipids (phospholipids, cholesterol) stabilized by apolipoproteins, mainly apoA-I and apoA-II. ApoA-I provides a structural scaffold and a functional ligand on the particle surface, and apoA-II modulates HDL structure-function and stability. We have probed the structural and compositional changes in HDL upon the onset of diabetes. Our goal is to test a hypothesis that increased triglyceride content decreases structural stability of plasma HDL. Blood samples were collected from cohorts of patients who were normolipidemic and normoglycemic (NL-HDL), diabetic with good glycemic control due to medication (GC-HDL), and newly diagnosed diabetic with poor glycemic control (PC-HDL). Lipoproteins were studied for biochemical composition, structure and stability by using circular dichroism spectroscopy, SDS, native gel electrophoresis, Western blotting, and negative staining electron microscopy. MALDI-TOF mass spectrometry shows the absence of post-translational modifications in all major apolipoproteins. Irrespective of the cohort, there is an inverse correlation between increased triglyceride content and lipoprotein stability. However, changes in HDL triglycerides associated with diabetes are not large enough to affect HDL stability. The results also suggest an increased degradation rate of HDL proteins in the PC-HDL group when compared to GC-HDL or NL-HDL, which is currently under investigation.

Structural remodeling of high-density lipoproteins in patients with diabetes mellitus

256th National Meeting (2018)

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