title: Lipoprotein hydrophobic core lipids are partially extruded to surface in smaller HDL: "Herniated" HDL, a common feature in diabetes.
abstract: Recent studies have shown that pharmacological increases in HDL cholesterol concentrations do not necessarily translate into clinical benefits for patients, raising concerns about its predictive value for cardiovascular events. Here we hypothesize that the size-modulated lipid distribution within HDL particles is compromised in metabolic disorders that have abnormal HDL particle sizes, such as type 2 diabetes mellitus (DM2). By using NMR spectroscopy combined with a biochemical volumetric model we determined the size and spatial lipid distribution of HDL subclasses in a cohort of 26 controls and 29 DM2 patients before and after two drug treatments, one with niacin plus laropiprant and another with fenofibrate as an add-on to simvastatin. We further characterized the HDL surface properties using atomic force microscopy and fluorescent probes to show an abnormal lipid distribution within smaller HDL particles, a subclass particularly enriched in the DM2 patients. The reduction in the size, force cholesterol esters and triglycerides to emerge from the HDL core to the surface, making the outer surface of HDL more hydrophobic. Interestingly, pharmacological interventions had no effect on this undesired configuration, which may explain the lack of clinical benefits in DM2 subjects.
authors.affiliation: Metabolomics Platform, Department of Electronic Engineering, Rovira i Virgili University, IISPV, Av. PaÏsos Catalans 26, 43007, Tarragona, Spain.|Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), C. Monforte de Lemos 3-5, 28029, Madrid, Spain.
authors.forename: Núria
authors.initials: N
authors.lastname: Amigó
authors.affiliation: Metabolomics Platform, Department of Electronic Engineering, Rovira i Virgili University, IISPV, Av. PaÏsos Catalans 26, 43007, Tarragona, Spain.|Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), C. Monforte de Lemos 3-5, 28029, Madrid, Spain.
authors.forename: Roger
authors.initials: R
authors.lastname: Mallol
authors.affiliation: Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), C. Monforte de Lemos 3-5, 28029, Madrid, Spain.|Vascular Medicine and Metabolism Unit, Research Unit on Lipids and Atherosclerosis, Sant Joan University Hospital, Rovira i Virgili University, IISPV, C. Sant Joan s/n, 43201, Reus, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Heras
authors.affiliation: Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), C. Monforte de Lemos 3-5, 28029, Madrid, Spain.|Endocrinology and Nutrition Department, Hospital Clinico Universitario, INCLIVA, Department of Medicine, University of Valencia, Av. Blasco Ibañez 17, 46010, Valencia, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Martínez-Hervás
authors.affiliation: Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), C. Monforte de Lemos 3-5, 28029, Madrid, Spain.|Institut d'Investigacions Biomèdiques (IIB) Sant Pau, Antoni M. Claret 167, 08025, Barcelona, spain.|Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona (UAB), Edifici M. Campus de la UAB, 08193, Bellaterra, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Blanco Vaca
authors.affiliation: Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), C. Monforte de Lemos 3-5, 28029, Madrid, Spain.|Institut d'Investigacions Biomèdiques (IIB) Sant Pau, Antoni M. Claret 167, 08025, Barcelona, spain.|Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona (UAB), Edifici M. Campus de la UAB, 08193, Bellaterra, Spain.
authors.forename: Joan Carles
authors.initials: JC
authors.lastname: Escolà-Gil
authors.affiliation: Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), C. Monforte de Lemos 3-5, 28029, Madrid, Spain.|Vascular Medicine and Metabolism Unit, Research Unit on Lipids and Atherosclerosis, Sant Joan University Hospital, Rovira i Virgili University, IISPV, C. Sant Joan s/n, 43201, Reus, Spain.
authors.forename: Núria
authors.initials: N
authors.lastname: Plana
authors.affiliation: Metabolomics Platform, Department of Electronic Engineering, Rovira i Virgili University, IISPV, Av. PaÏsos Catalans 26, 43007, Tarragona, Spain.|Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), C. Monforte de Lemos 3-5, 28029, Madrid, Spain.
authors.forename: Óscar
authors.initials: Ó
authors.lastname: Yanes
authors.affiliation: Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), C. Monforte de Lemos 3-5, 28029, Madrid, Spain.|Vascular Medicine and Metabolism Unit, Research Unit on Lipids and Atherosclerosis, Sant Joan University Hospital, Rovira i Virgili University, IISPV, C. Sant Joan s/n, 43201, Reus, Spain.
authors.forename: Lluís
authors.initials: L
authors.lastname: Masana
authors.affiliation: Metabolomics Platform, Department of Electronic Engineering, Rovira i Virgili University, IISPV, Av. PaÏsos Catalans 26, 43007, Tarragona, Spain.|Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), C. Monforte de Lemos 3-5, 28029, Madrid, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Correig
mesh_terms: D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D011345:Fenofibrate / Q000008:administration & dosage; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D007211:Indoles / Q000008:administration & dosage; D050356:Lipid Metabolism / Q000187:drug effects; D008055:Lipids / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D018625:Microscopy, Atomic Force; D008875:Middle Aged; D009525:Niacin; D019821:Simvastatin / Q000008:administration & dosage; D013499:Surface Properties / Q000187:drug effects; D014280:Triglycerides / Q000737:chemistry / Q000378:metabolism
chemical_list: D008076:Cholesterol, HDL; D005456:Fluorescent Dyes; D007211:Indoles; D008055:Lipids; C518174:MK-0524; D014280:Triglycerides; D009525:Niacin; D019821:Simvastatin; D011345:Fenofibrate