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

Samino S, Vinaixa M, Díaz M, Beltran A, Rodríguez MA, Mallol R, Heras M, Cabre A, Garcia L, Canela N, de Zegher F, Correig X, Ibáñez L, Yanes O - Sci Rep (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus

Identified and quantified metabolites involved in the γ-glutamyl cycle.The scatter plots show the abundance of individual metabolites in control and HIAE serum samples and trimmed mean (P < 0.05) (control in red and HIAE in blue). Glycine was measured by 1H-NMR and the other metabolites by LC-QqQ MS.
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f3: Identified and quantified metabolites involved in the γ-glutamyl cycle.The scatter plots show the abundance of individual metabolites in control and HIAE serum samples and trimmed mean (P < 0.05) (control in red and HIAE in blue). Glycine was measured by 1H-NMR and the other metabolites by LC-QqQ MS.

Mentions: The biosynthesis of glutathione (by quantifying reduced glutathione), the redox status (by quantifying the ratio of reduced to oxidized glutathione) and intermediates of the γ-glutamyl cycle were also elevated in HIAE girls (Fig. 3). These data demonstrate a redox dysregulation in HIAE girls.


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

Samino S, Vinaixa M, Díaz M, Beltran A, Rodríguez MA, Mallol R, Heras M, Cabre A, Garcia L, Canela N, de Zegher F, Correig X, Ibáñez L, Yanes O - Sci Rep (2015)

Identified and quantified metabolites involved in the γ-glutamyl cycle.The scatter plots show the abundance of individual metabolites in control and HIAE serum samples and trimmed mean (P < 0.05) (control in red and HIAE in blue). Glycine was measured by 1H-NMR and the other metabolites by LC-QqQ MS.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4477239&req=5

f3: Identified and quantified metabolites involved in the γ-glutamyl cycle.The scatter plots show the abundance of individual metabolites in control and HIAE serum samples and trimmed mean (P < 0.05) (control in red and HIAE in blue). Glycine was measured by 1H-NMR and the other metabolites by LC-QqQ MS.
Mentions: The biosynthesis of glutathione (by quantifying reduced glutathione), the redox status (by quantifying the ratio of reduced to oxidized glutathione) and intermediates of the γ-glutamyl cycle were also elevated in HIAE girls (Fig. 3). These data demonstrate a redox dysregulation in HIAE girls.

Bottom Line: 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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus