High-Density Lipoprotein Alterations in Type 2 Diabetes and Obesity

Abstract

Alterations affecting high-density lipoproteins (HDLs) are one of the various abnormalities observed in dyslipidemia in type 2 diabetes mellitus (T2DM) and obesity. Kinetic studies have demonstrated that the catabolism of HDL particles is accelerated. Both the size and the lipidome and proteome of HDL particles are significantly modified, which likely contributes to some of the functional defects of HDLs. Studies on cholesterol efflux capacity have yielded heterogeneous results, ranging from a defect to an improvement. Several studies indicate that HDLs are less able to inhibit the nuclear factor kappa-B (NF-κB) proinflammatory pathway, and subsequently, the adhesion of monocytes on endothelium and their recruitment into the subendothelial space. In addition, the antioxidative function of HDL particles is diminished, thus facilitating the deleterious effects of oxidized low-density lipoproteins on vasculature. Lastly, the HDL-induced activation of endothelial nitric oxide synthase is less effective in T2DM and metabolic syndrome, contributing to several HDL functional defects, such as an impaired capacity to promote vasodilatation and endothelium repair, and difficulty counteracting the production of reactive oxygen species and inflammation.

Healthy lifestyle linked to innate immunity and lipoprotein metabolism: a cross-sectional comparison using untargeted proteomics

“…Several blood apolipoproteins were higher in LIFE versus CON including apolipoprotein A-1, D, and C-1 that are involved in HDL metabolism 43 . HDL-cholesterol was significantly higher in LIFE versus CON, and both lower body fat and higher physical activity levels have been related to elevated HDL-cholesterol 43 , 44 . Other studies have shown extensive effects of weight loss on apolipoproteins 22 , 36 , 38 .…”

Decoding cardiovascular risks: analyzing type 2 diabetes mellitus and ASCVD gene expression

“…found that in patients with T2DM, elevated triglyceride levels tended to be associated with an increased risk of CVD, which may suggest that blood glucose levels play a significant role in the development of ASCVD ( 19 ) ( Tables 2 , 3 ). However, the role of TG in ASCVD was not widely accepted initially, but they are now recognized as necessary ( 20 – 22 ).…”

Acute myocardial infarction preferentially alters low-abundant, long-chain unsaturated phospholipid and sphingolipid species in plasma high-density lipoprotein subpopulations

“…Multiplied by low circulating HDL concentrations, such deficiency in HDL composition and function can be expected to contribute to accelerated atherogenesis observed in this clinical condition. Indeed, similar abnormalities of the HDL lipidome occur under conditions associated with elevated cardiovascular risk, including familial apoA-I deficiency [ 39 ] and insulin resistance [ 22 , 23 ]. As a corollary, normalization of HDL phospho- and/or sphingolipid composition (i.e.…”

“…These compositional alterations involve enrichment in saturated fatty acids (SFAs) at the expense of polyunsaturated fatty acids (PUFAs). Interestingly, similar abnormalities, including elevated content of LPC and SFA paralleled by reduced content of plasmalogens, SM, phospholipid and PUFAs, occur in HDL obtained from patients with Type 2 diabetes and Metabolic Syndrome which are major risk factors for AMI [ 22 , 23 ].…”