Normal HDL Cholesterol Efflux and Anti-Inflammatory Capacities in Type 2 Diabetes Despite Lipidomic Abnormalities

• Published in: The journal of clinical endocrinology and metabolism Vol. 107; no. 9; pp. e3816 - e3823
• Main Authors: Denimal, Damien, Benanaya, Sara, Monier, Serge, Simoneau, Isabelle, Pais de Barros, Jean-Paul, Le Goff, Wilfried, Bouillet, Benjamin, Vergès, Bruno, Duvillard, Laurence
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01.09.2022; Endocrine Society
• Subjects: Analysis; Anti-inflammatory drugs; Blood cholesterol; Cell adhesion & migration; Cell adhesion molecules; Ceramides; Cholesterol; Chromatography; Diabetes; Diabetes mellitus (non-insulin dependent); Endothelial cells; Ethylenediaminetetraacetic acid; High density lipoprotein; Inflammation; Intercellular adhesion molecule 1; Life Sciences; Lipids; Liquid chromatography; Macrophages; Mass spectrometry; Mass spectroscopy; Medical research; Medicine, Experimental; Online Only; Phosphates; Phosphatidylethanolamine; Phospholipids; Sphingolipids; Sphingosine; Sphingosine 1-phosphate; Tumor necrosis factor; Tumor necrosis factor-α; Type 2 diabetes; Vascular cell adhesion molecule 1; France; HDL; type 2 diabetes; anti-inflammatory effect; cholesterol efflux; lipidomics
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/clinem/dgac339

Abstract Objective To assess whether, in type 2 diabetes (T2D) patients, lipidomic abnormalities in high-density lipoprotein (HDL) are associated with impaired cholesterol efflux capacity and anti-inflammatory effect, 2 pro-atherogenic abnormalities. Design and Methods This is a secondary analysis of the Lira-NAFLD study, including 20 T2D patients at T0 and 25 control subjects. Using liquid chromatography/tandem mass spectrometry, we quantified 110 species of the main HDL phospholipids and sphingolipids. Cholesterol efflux capacity was measured on THP-1 macrophages. The anti-inflammatory effect of HDL was measured as their ability to inhibit the tumor necrosis factor α (TNFα)-induced expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular cell adhesion molecule-1 (ICAM-1) on human vascular endothelial cells (HUVECs). Results The cholesterol-to-triglyceride ratio was decreased in HDL from T2D patients compared with controls (-46%, P = 0.00008). As expressed relative to apolipoprotein AI, the amounts of phosphatidylcholines, sphingomyelins, and sphingosine-1-phosphate were similar in HDL from T2D patients and controls. Phosphatidylethanolamine-based plasmalogens and ceramides (Cer) were, respectively, 27% (P = 0.038) and 24% (P = 0.053) lower in HDL from T2D patients than in HDL from controls, whereas phosphatidylethanolamines were 41% higher (P = 0.026). Cholesterol efflux capacity of apoB-depleted plasma was similar in T2D patients and controls (36.2 ± 4.3 vs 35.5 ± 2.8%, P = 0.59). The ability of HDL to inhibit the TNFα-induced expression of both VCAM-1 and ICAM-1 at the surface of HUVECs was similar in T2D patients and controls (-70.6 ± 16.5 vs -63.5 ± 18.7%, P = 0.14; and -62.1 ± 13.2 vs -54.7 ± 17.7%, P = 0.16, respectively). Conclusion Despite lipidomic abnormalities, the cholesterol efflux and anti-inflammatory capacities of HDL are preserved in T2D patients.