title: Metabolomics reveals impaired maturation of HDL particles in adolescents with hyperinsulinaemic androgen excess.
abstract: Hyperinsulinaemic androgen excess (HIAE) in prepubertal and pubertal girls usually precedes a broader pathological phenotype in adulthood that is associated with anovulatory infertility, metabolic syndrome and type 2 diabetes. The metabolic derangements that determine these long-term health risks remain to be clarified. Here we use NMR and MS-based metabolomics to show that serum levels of methionine sulfoxide in HIAE girls are an indicator of the degree of oxidation of methionine-148 residue in apolipoprotein-A1. Oxidation of apo-A1 in methionine-148, in turn, leads to an impaired maturation of high-density lipoproteins (HDL) that is reflected in a decline of large HDL particles. Notably, such metabolic alterations occur in the absence of impaired glucose tolerance, hyperglycemia and hypertriglyceridemia, and were partially restored after 18 months of treatment with a low-dose combination of pioglitazone, metformin and flutamide.
authors.affiliation: 1] Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), C/ Monforte de Lemos 3-5, 28029 Madrid, Spain [2] Centre for Omic Sciences (COS), Rovira i Virgili University, Avinguda Universitat 3, 43204 Reus, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Samino
authors.affiliation: 1] Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), C/ Monforte de Lemos 3-5, 28029 Madrid, Spain [2] Department of Electronic Engineering, Rovira i Virgili University, Avinguda Països Catalans 26, 43007 Tarragona, Spain [3] Centre for Omic Sciences (COS), Rovira i Virgili University, Avinguda Universitat 3, 43204 Reus, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Vinaixa
authors.affiliation: 1] Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), C/ Monforte de Lemos 3-5, 28029 Madrid, Spain [2] Endocrinology Unit, Hospital Sant Joan de Déu, University of Barcelona, Passeig de Sant Joan de Déu 2, 08950 Esplugues, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Díaz
authors.affiliation: 1] Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), C/ Monforte de Lemos 3-5, 28029 Madrid, Spain [2] Centre for Omic Sciences (COS), Rovira i Virgili University, Avinguda Universitat 3, 43204 Reus, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Beltran
authors.affiliation: 1] Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), C/ Monforte de Lemos 3-5, 28029 Madrid, Spain [2] Centre for Omic Sciences (COS), Rovira i Virgili University, Avinguda Universitat 3, 43204 Reus, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Rodríguez
authors.affiliation: 1] Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), C/ Monforte de Lemos 3-5, 28029 Madrid, Spain [2] Department of Electronic Engineering, Rovira i Virgili University, Avinguda Països Catalans 26, 43007 Tarragona, Spain.
authors.forename: Roger
authors.initials: R
authors.lastname: Mallol
authors.affiliation: 1] Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), C/ Monforte de Lemos 3-5, 28029 Madrid, Spain [2] Research Unit on Lipids and Atherosclerosis, Sant Joan University Hospital, Universitat Rovira i Virgili, IISPV, Carrer Sant Llorenç 21, 43201 Reus, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Heras
authors.affiliation: 1] Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), C/ Monforte de Lemos 3-5, 28029 Madrid, Spain [2] Research Unit on Lipids and Atherosclerosis, Sant Joan University Hospital, Universitat Rovira i Virgili, IISPV, Carrer Sant Llorenç 21, 43201 Reus, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Cabre
authors.affiliation: Centre for Omic Sciences (COS), Rovira i Virgili University, Avinguda Universitat 3, 43204 Reus, Spain.
authors.forename: Lorena
authors.initials: L
authors.lastname: Garcia
authors.affiliation: Centre for Omic Sciences (COS), Rovira i Virgili University, Avinguda Universitat 3, 43204 Reus, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Canela
authors.affiliation: Paediatric Endocrinology, University Hospital Gasthuisberg, UZ Herestraat 49, 3000 Leuven, University of Leuven, Belgium.
authors.forename: Francis
authors.initials: F
authors.lastname: de Zegher
authors.affiliation: 1] Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), C/ Monforte de Lemos 3-5, 28029 Madrid, Spain [2] Department of Electronic Engineering, Rovira i Virgili University, Avinguda Països Catalans 26, 43007 Tarragona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Correig
authors.affiliation: 1] Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), C/ Monforte de Lemos 3-5, 28029 Madrid, Spain [2] Endocrinology Unit, Hospital Sant Joan de Déu, University of Barcelona, Passeig de Sant Joan de Déu 2, 08950 Esplugues, Barcelona, Spain.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Ibáñez
authors.affiliation: 1] Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), C/ Monforte de Lemos 3-5, 28029 Madrid, Spain [2] Department of Electronic Engineering, Rovira i Virgili University, Avinguda Països Catalans 26, 43007 Tarragona, Spain [3] Centre for Omic Sciences (COS), Rovira i Virgili University, Avinguda Universitat 3, 43204 Reus, Spain.
authors.forename: Oscar
authors.initials: O
authors.lastname: Yanes
mesh_terms: D000293:Adolescent; D000728:Androgens / Q000009:adverse effects*; D016632:Apolipoprotein A-I / Q000378:metabolism; D002853:Chromatography, Liquid; D004703:Endocrine System / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000096:biosynthesis; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood* / Q000188:drug therapy / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood; D009682:Magnetic Resonance Spectroscopy; D055442:Metabolome; D055432:Metabolomics; D008715:Methionine / Q000031:analogs & derivatives; D010084:Oxidation-Reduction; D012307:Risk Factors; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: C505693:APOA1 protein, human; D000728:Androgens; D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D008715:Methionine; D005978:Glutathione; C013111:methionine sulfoxide