Damien Denimal1, Amandine Nguyen2, Jean-Paul Pais de Barros3, Benjamin Bouillet4, Jean-Michel Petit4, Bruno Vergès4, Laurence Duvillard5. 1. National Institute of Health and Medical Research Unit 866, University of Bourgogne and Franche Comté, Faculty of Health Sciences, Dijon, France; Department of Biochemistry, University Hospital Dijon, Dijon, France. 2. Department of Endocrinology and Metabolic Diseases, University Hospital Dijon, Dijon, France. 3. Lipidomic Platform, University of Bourgogne and Franche Comté, Dijon, France. 4. National Institute of Health and Medical Research Unit 866, University of Bourgogne and Franche Comté, Faculty of Health Sciences, Dijon, France; Department of Endocrinology and Metabolic Diseases, University Hospital Dijon, Dijon, France. 5. National Institute of Health and Medical Research Unit 866, University of Bourgogne and Franche Comté, Faculty of Health Sciences, Dijon, France; Department of Biochemistry, University Hospital Dijon, Dijon, France. Electronic address: laurence.duvillard@chu-dijon.fr.
Abstract
OBJECTIVE: Phospholipids and sphingolipids play a critical role in the protective effects of HDL against atherosclerosis. These properties are impaired in patients with metabolic syndrome, before the development of diabetes. We thus investigated whether HDL from patients with metabolic syndrome but normal fasting glycaemia present abnormalities in their sphingophospholipid profile. METHODS: Using liquid chromatography/tandem mass spectrometry, we quantified the different species of the main phospholipids and sphingolipids in the HDL2 and HDL3 from 26 obese patients with metabolic syndrome but normal fasting glycaemia and 50 controls. RESULTS: Phosphatidylcholines, when expressed as the relative amount compared with total phospholipids and sphingolipids, were similar in both HDL2 and HDL3 in the two groups. Lysophosphatidylcholines were 41% (p = 0.0002) and 86% (p < 0.0001) higher in HDL2 and HDL3, respectively, from patients with metabolic syndrome than in those from controls. Phosphatidylinositols were also higher in HDL2 and HDL3 (respectively, +60 and + 103% (p < 0.0001)). In contrast, both HDL2 and HDL3 from patients with metabolic syndrome showed lower proportions of phosphatidylethanolamine-based plasmalogens (respectively -78 and -73%, p < 0.0001), phosphatidylcholine-based plasmalogens (respectively -44 and -53%, p < 0.0001), d18:1-sphingosine-1-phosphate (respectively -52 and -38%, p < 0.0001) and sphingomyelins (respectively -19% (p < 0.0001) and -24% (p = 0.0006)), than did controls. Moreover, we observed a decrease in C18:2 fatty acid-containing phospholipids and an increase in C20:4 fatty acid-containing phospholipids. CONCLUSION: The sphingophospholipidome of HDL from normoglycaemic obese patients with metabolic syndrome is profoundly modified, before the dysregulation of glycaemia. Most of the changes observed have pejorative effect in terms of vascular protection.
OBJECTIVE:Phospholipids and sphingolipids play a critical role in the protective effects of HDL against atherosclerosis. These properties are impaired in patients with metabolic syndrome, before the development of diabetes. We thus investigated whether HDL from patients with metabolic syndrome but normal fasting glycaemia present abnormalities in their sphingophospholipid profile. METHODS: Using liquid chromatography/tandem mass spectrometry, we quantified the different species of the main phospholipids and sphingolipids in the HDL2 and HDL3 from 26 obesepatients with metabolic syndrome but normal fasting glycaemia and 50 controls. RESULTS:Phosphatidylcholines, when expressed as the relative amount compared with total phospholipids and sphingolipids, were similar in both HDL2 and HDL3 in the two groups. Lysophosphatidylcholines were 41% (p = 0.0002) and 86% (p < 0.0001) higher in HDL2 and HDL3, respectively, from patients with metabolic syndrome than in those from controls. Phosphatidylinositols were also higher in HDL2 and HDL3 (respectively, +60 and + 103% (p < 0.0001)). In contrast, both HDL2 and HDL3 from patients with metabolic syndrome showed lower proportions of phosphatidylethanolamine-based plasmalogens (respectively -78 and -73%, p < 0.0001), phosphatidylcholine-based plasmalogens (respectively -44 and -53%, p < 0.0001), d18:1-sphingosine-1-phosphate (respectively -52 and -38%, p < 0.0001) and sphingomyelins (respectively -19% (p < 0.0001) and -24% (p = 0.0006)), than did controls. Moreover, we observed a decrease in C18:2 fatty acid-containing phospholipids and an increase in C20:4 fatty acid-containing phospholipids. CONCLUSION: The sphingophospholipidome of HDL from normoglycaemic obesepatients with metabolic syndrome is profoundly modified, before the dysregulation of glycaemia. Most of the changes observed have pejorative effect in terms of vascular protection.
Authors: Mathias Cardner; Mustafa Yalcinkaya; Sandra Goetze; Edlira Luca; Miroslav Balaz; Monika Hunjadi; Johannes Hartung; Andrej Shemet; Nicolle Kränkel; Silvija Radosavljevic; Michaela Keel; Alaa Othman; Gergely Karsai; Thorsten Hornemann; Manfred Claassen; Gerhard Liebisch; Erick Carreira; Andreas Ritsch; Ulf Landmesser; Jan Krützfeldt; Christian Wolfrum; Bernd Wollscheid; Niko Beerenwinkel; Lucia Rohrer; Arnold von Eckardstein Journal: JCI Insight Date: 2020-01-16
Authors: Gabriele Mocciaro; Simona D'Amore; Benjamin Jenkins; Richard Kay; Antonio Murgia; Luis Vicente Herrera-Marcos; Stefanie Neun; Alice P Sowton; Zoe Hall; Susana Alejandra Palma-Duran; Giuseppe Palasciano; Frank Reimann; Andrew Murray; Patrizia Suppressa; Carlo Sabbà; Antonio Moschetta; Albert Koulman; Julian L Griffin; Michele Vacca Journal: Int J Mol Sci Date: 2022-06-17 Impact factor: 6.208