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

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.

Keywords: HDL; anti-inflammatory effect; cholesterol efflux; lipidomics; type 2 diabetes.

Figure 1.

HDL anti-inflammatory effect and ability to induce cholesterol efflux. (A) Anti-inflammatory effect was measured on HUVEC incubated with HDL (800 µg/mL apoAI) for 16 hours before stimulating VCAM-1 and ICAM-1 expression by 100 UI/mL recombinant TNFα. HDL-induced inhibition was calculated by comparison with TNFα-induced VCAM-1 and ICAM-1 expression without HDL. (B) Cholesterol efflux was measured on THP-1 macrophages loaded with Bodipy-labeled cholesterol and incubated with apolipoprotein B-depleted plasma (5% v/v) for 4 hours. Percent of efflux was calculated with the following formula: [fluorescence in supernatant ÷ (fluorescence in supernatant + fluorescence in lysat)] × 100. NS, not significant.