Metabolomics reveals impaired maturation of HDL particles in adolescents with hyperinsulinaemic androgen excess

Sara Samino; Maria Vinaixa; Marta Díaz; Antoni Beltran; Miguel A. Rodríguez; Roger Mallol; Mercedes Heras; Anna Cabre; Lorena Garcia; Nuria Canela; Francis De Zegher; Xavier Correig; Lourdes Ibáñez; Oscar Yanes

doi:10.1038/srep11496

Metabolomics reveals impaired maturation of HDL particles in adolescents with hyperinsulinaemic androgen excess

Sara Samino, Maria Vinaixa, Marta Díaz, Antoni Beltran, Miguel A. Rodríguez, Roger Mallol, Mercedes Heras, Anna Cabre, Lorena Garcia, Nuria Canela, Francis De Zegher, Xavier Correig, Lourdes Ibáñez, Oscar Yanes

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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.

Idioma original	Anglès
Número d’article	11496
Revista	Scientific Reports
Volum	5
DOIs	https://doi.org/10.1038/srep11496
Estat de la publicació	Publicada - 23 de juny 2015
Publicat externament	Sí

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Samino, S., Vinaixa, M., Díaz, M., Beltran, A., Rodríguez, M. A., Mallol, R., Heras, M., Cabre, A., Garcia, L., Canela, N., De Zegher, F., Correig, X., Ibáñez, L., & Yanes, O. (2015). Metabolomics reveals impaired maturation of HDL particles in adolescents with hyperinsulinaemic androgen excess. Scientific Reports, 5, Article 11496. https://doi.org/10.1038/srep11496

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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.",

author = "Sara Samino and Maria Vinaixa and Marta D{\'i}az and Antoni Beltran and Rodr{\'i}guez, {Miguel A.} and Roger Mallol and Mercedes Heras and Anna Cabre and Lorena Garcia and Nuria Canela and {De Zegher}, Francis and Xavier Correig and Lourdes Ib{\'a}{\~n}ez and Oscar Yanes",

note = "Funding Information: We thank Dr. Carles Lerin and Dr. Pablo Garcia-Roves for helpful discussions. We thank the financial support from the Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), an initiative of Instituto de Investigacion Carlos III (ISCIII), the Fondo Europeo de Desarrollo Regional (FEDER) (Madrid, Spain), and the Spanish Ministry of Economy and Competitiveness grants SAF2011-30578 (to OY) and PI09/90444 (to LI). Publisher Copyright: {\textcopyright} 2015 Scientific Reports.",

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doi = "10.1038/srep11496",

language = "English",

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T1 - Metabolomics reveals impaired maturation of HDL particles in adolescents with hyperinsulinaemic androgen excess

AU - Samino, Sara

AU - Vinaixa, Maria

AU - Díaz, Marta

AU - Beltran, Antoni

AU - Rodríguez, Miguel A.

AU - Mallol, Roger

AU - Heras, Mercedes

AU - Cabre, Anna

AU - Garcia, Lorena

AU - Canela, Nuria

AU - De Zegher, Francis

AU - Correig, Xavier

AU - Ibáñez, Lourdes

AU - Yanes, Oscar

N1 - Funding Information: We thank Dr. Carles Lerin and Dr. Pablo Garcia-Roves for helpful discussions. We thank the financial support from the Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), an initiative of Instituto de Investigacion Carlos III (ISCIII), the Fondo Europeo de Desarrollo Regional (FEDER) (Madrid, Spain), and the Spanish Ministry of Economy and Competitiveness grants SAF2011-30578 (to OY) and PI09/90444 (to LI). Publisher Copyright: © 2015 Scientific Reports.

PY - 2015/6/23

Y1 - 2015/6/23

N2 - 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.

AB - 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.

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Metabolomics reveals impaired maturation of HDL particles in adolescents with hyperinsulinaemic androgen excess

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