Progressive, Qualitative, and Quantitative Alterations in HDL Lipidome from Healthy Subjects to Patients with Prediabetes and Type 2 Diabetes

Kostara, Christina; Karakitsou, Kiriaki S.; Florentin, Matilda; Bairaktari, Eleni; Tsimihodimos, Vasilis

doi:10.3390/metabo12080683

Cited by 11 publications

(18 citation statements)

References 68 publications

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“…As mentioned above, HDL particles are enriched in TGs in patients with T2DM [ 18 , 19 , 39 , 40 , 41 ], obesity [ 42 ], insulin resistance [ 40 , 43 ] or MetS [ 44 ]. The replacement of CE by TG molecules in HDLs affects the conformation of apoA-I [ 45 ], which could modulate binding to receptors and the functions of HDLs.…”

Section: Hdl Size and Compositionmentioning

confidence: 99%

“…The expression of results in relation to either total HDL mass, total HDL lipids, or apoA-I levels makes it challenging to compare between studies. The HDL content in total PLs has been found to be either decreased in T2DM when the results are expressed in relation to total lipids [ 40 ], or normal when the results are expressed in relation to total mass or total lipids [ 18 , 41 ].…”

Section: Hdl Size and Compositionmentioning

confidence: 99%

“…When the results are expressed in relation to apoA-I, the HDL content in PCs and SMs in T2DM has been found to be either normal or decreased [ 19 , 41 ]. When the results are expressed in relation to total HDL lipids, PCs and SMs have been found decreased in T2DM HDLs [ 40 ]. In addition, Cardner et al reported a decrease in PC36:2 and 34:2, but the way in which results are expressed is unclear [ 22 ].…”

Section: Hdl Size and Compositionmentioning

confidence: 99%

“…In addition, Cardner et al reported a decrease in PC36:2 and 34:2, but the way in which results are expressed is unclear [ 22 ]. The SM/PC ratio, a marker of surface rigidity, has been found to be either unaffected or decreased [ 19 , 40 ].…”

Section: Hdl Size and Compositionmentioning

confidence: 99%

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High-Density Lipoprotein Alterations in Type 2 Diabetes and Obesity

et al. 2023

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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.

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Section: Hdl Size and Compositionmentioning

confidence: 99%

Section: Hdl Size and Compositionmentioning

confidence: 99%

Section: Hdl Size and Compositionmentioning

confidence: 99%

Section: Hdl Size and Compositionmentioning

confidence: 99%

See 2 more Smart Citations

High-Density Lipoprotein Alterations in Type 2 Diabetes and Obesity

et al. 2023

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“…This is probably due, at least in part, to the difficulties in applying time-consuming lipoprotein purification procedures requiring specific expertise to large scale studies. Most of the published studies dealt with HDL showing alterations of the phospho- and sphingo-lipidomes in type 1 diabetes [ 26 ], type 2 diabetes [ 27 , 28 ], obesity and metabolic syndrome [ 29 , 30 ], dyslipidemia [ 31 , 32 ], and experimental atherosclerosis [ 33 , 34 ]. Some of them reported normalization of the HDL lipidome in metabolic syndrome following either Pitavastatin treatment [ 35 ] or weight loss and physical activity [ 36 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular Characterization of Plasma HDL, LDL, and VLDL Lipids Cargos from Atherosclerotic Patients with Advanced Carotid Lesions: A Preliminary Report

Nieddu

Michelucci

Formato

et al. 2022

IJMS

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Carotid atherosclerosis represents a relevant healthcare problem, since unstable plaques are responsible for approximately 15% of neurologic events, namely transient ischemic attack and stroke. Although statins treatment has proven effective in reducing LDL-cholesterol and the onset of acute clinical events, a residual risk may persist suggesting the need for the detection of reliable molecular markers useful for the identification of patients at higher risk regardless of optimal medical therapy. In this regard, several lines of evidence show a relationship among specific biologically active plasma lipids, atherosclerosis, and acute clinical events. We performed a Selected Reaction Monitoring-based High Performance Liquid Chromatography-tandem Mass Spectrometry (SRM-based HPLC-MS/MS) analysis on plasma HDL, LDL, and VLDL fractions purified, by isopycnic salt gradient ultracentrifugation, from twenty-eight patients undergoing carotid endarterectomy, having either a “hard” or a “soft” plaque, with the aim of characterizing the specific lipidomic patterns associated with features of carotid plaque instability. One hundred and thirty lipid species encompassing different lipid (sub)classes were monitored. Supervised multivariate analysis showed that lipids belonging to phosphatidylethanolamine (PE), sphingomyelin (SM), and diacylglycerol (DG) classes mostly contribute to discrimination within each lipoprotein fraction according to the plaque typology. Differential analysis evidenced a significant dysregulation of LDL PE (38:6), SM (32:1), and SM (32:2) between the two groups of patients (adj. p-value threshold = 0.05 and log2FC ≥ |0.58|). Using this approach, some LDL-associated markers of plaque vulnerability have been identified, in line with the current knowledge of the key roles of these phospholipids in lipoprotein metabolism and cardiovascular disease. This proof-of-concept study reports promising results, showing that lipoprotein lipidomics may present a valuable approach for identifying new biomarkers of potential clinical relevance.

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Chewing the fat: How lipidomics is changing our understanding of human health and disease in 2022

Géhin

Fowler

Trivedi

2023

Analytical Science Advances

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Lipids are biological molecules that play vital roles in all living organisms. They perform many cellular functions, such as 1) forming cellular and subcellular membranes, 2) storing and using energy, and 3) serving as chemical messengers during intra‐ and inter‐cellular signal transduction. The large‐scale study of the pathways and networks of cellular lipids in biological systems is called “lipidomics” and is one of the fastest‐growing omics technologies of the last two decades. With state‐of‐the‐art mass spectrometry instrumentation and sophisticated data handling, clinical studies show how human lipid composition changes in health and disease, thereby making it a valuable medium to collect for clinical applications, such as disease diagnostics, therapeutic decision‐making, and drug development. This review gives a comprehensive overview of current workflows used in clinical research, from sample collection and preparation to data and clinical interpretations. This is followed by an appraisal of applications in 2022 and a perspective on the exciting future of clinical lipidomics.

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Progressive, Qualitative, and Quantitative Alterations in HDL Lipidome from Healthy Subjects to Patients with Prediabetes and Type 2 Diabetes

Cited by 11 publications

References 68 publications

High-Density Lipoprotein Alterations in Type 2 Diabetes and Obesity

High-Density Lipoprotein Alterations in Type 2 Diabetes and Obesity

Molecular Characterization of Plasma HDL, LDL, and VLDL Lipids Cargos from Atherosclerotic Patients with Advanced Carotid Lesions: A Preliminary Report

Chewing the fat: How lipidomics is changing our understanding of human health and disease in 2022

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