Glycation of HDL blunts its anti-inflammatory and cholesterol efflux capacities in vitro, but has no effect in poorly controlled type 1 diabetes subjects

• Published in: Journal of diabetes and its complications 2020-12, Vol.34 (12), p.107693-107693, Article 107693
• Main Authors: Gomes Kjerulf, Diego, Wang, Shari, Omer, Mohamed, Pathak, Asha, Subramanian, Savitha, Han, Chang Yeop, Tang, Chongren, den Hartigh, Laura J., Shao, Baohai, Chait, Alan
• Format: Article
• Language: English
• Subjects: Adipocytes; Cholesterol; Cholesterol efflux; Diabetes; Fatty acids; Gene expression; Glycation; Human subjects; Hyperglycemia; Inflammation; Lipids; Macrophages; Metabolic syndrome; Proteins
• ISSN: 1056-8727; 1873-460X
• DOI: 10.1016/j.jdiacomp.2020.107693

High-density lipoproteins (HDL) modified by glycation have been reported to be dysfunctional. Little is known regarding the anti-inflammatory effects on adipocytes of glycated HDL. We tested whether modification of HDL in vitro by glycolaldehyde (GAD), malondialdehyde (MDA) or glucose affected HDL's anti-inflammatory properties and ability to promote cholesterol efflux. To determine whether similar changes occur in vivo, we examined modifications of apolipoprotein A1 (APOA1) and APOA2 and anti-inflammatory and cholesterol efflux properties of HDL isolated from subjects with type 1 diabetes in poor glycemic control. In vitro modification with both GAD and MDA blunted HDL's ability to inhibit palmitate-induced inflammation and cholesterol efflux in adipocytes. Modification of HDL by glucose had little impact on HDL function, like the response using HDL isolated from subjects with diabetes. Mass spectrophotometric analysis revealed that lysine residues in APOA1 and APOA2 of HDL modified by GAD and MDA in vitro differed from those modified by glucose, which resembled that seen with HDL from patients with type1 diabetes. Modification of lysine residues in HDL by GAD and MDA in vitro does not mirror the HDL glycation in vivo in patients with diabetes, but resembles HDL modified in vitro by glucose. •In vitro glycation of HDL affects its ability to inhibit inflammation in adipocytes.•HDL glycated in vitro also has impaired cholesterol efflux capacity.•However HDL from poorly controlled type 1 patients functions normally.•In vitro and in vivo glycation result in different modifications detected by MS.•Glycation of HDL in vitro differs from that observed in vivo.