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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

Lipoprotein profile measured by NMR spectroscopy.(A) Bipolar LED pulse sequence 1H NMR spectra of a HIAE serum showing the fitting of the methyl band using seven Lorentzian functions derived from our previously described methodology18. (B) The amount of lipoprotein particles is expressed as the percentage of particles for every lipoprotein subclass with regard to the total number of particles. Row-wise normalized areas showed as mean±sem. VLDL: very low-density lipoprotein, lLDL: large low-density lipoprotein, sLDL: small low-density lipoprotein, lHDL: large high-density lipoprotein, mHDL: medium high-density lipoprotein, sHDL: small high-density lipoprotein
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f1: Lipoprotein profile measured by NMR spectroscopy.(A) Bipolar LED pulse sequence 1H NMR spectra of a HIAE serum showing the fitting of the methyl band using seven Lorentzian functions derived from our previously described methodology18. (B) The amount of lipoprotein particles is expressed as the percentage of particles for every lipoprotein subclass with regard to the total number of particles. Row-wise normalized areas showed as mean±sem. VLDL: very low-density lipoprotein, lLDL: large low-density lipoprotein, sLDL: small low-density lipoprotein, lHDL: large high-density lipoprotein, mHDL: medium high-density lipoprotein, sHDL: small high-density lipoprotein

Mentions: Dyslipidemia is a risk factor linked to metabolic syndrome, T2D and CVD17. Here we studied the lipoprotein profile of HIAE girls beyond the standard measurement of cholesterol content of lipoproteins. By using an advanced lipoprotein analysis based on nuclear magnetic resonance (NMR) spectroscopy18, 1H-NMR allow to characterize the size and relative abundance of lipoprotein particles in serum. The use of NMR-derived lipoprotein subclasses improved cardiovascular risk stratification for subclinical atherosclerosis in comparison to conventional lipids19. Briefly, depending on the size of the lipoprotein particle, the methyl moieties of the lipids in lipoproteins resonate at slightly different frequencies, the smaller particles resonating at lower frequencies (Fig. 1a). Our NMR-derived lipoprotein subclasses were defined as VLDL, large LDL, small LDL, large HDL, medium HDL, and small HDL.


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)

Lipoprotein profile measured by NMR spectroscopy.(A) Bipolar LED pulse sequence 1H NMR spectra of a HIAE serum showing the fitting of the methyl band using seven Lorentzian functions derived from our previously described methodology18. (B) The amount of lipoprotein particles is expressed as the percentage of particles for every lipoprotein subclass with regard to the total number of particles. Row-wise normalized areas showed as mean±sem. VLDL: very low-density lipoprotein, lLDL: large low-density lipoprotein, sLDL: small low-density lipoprotein, lHDL: large high-density lipoprotein, mHDL: medium high-density lipoprotein, sHDL: small high-density lipoprotein
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1: Lipoprotein profile measured by NMR spectroscopy.(A) Bipolar LED pulse sequence 1H NMR spectra of a HIAE serum showing the fitting of the methyl band using seven Lorentzian functions derived from our previously described methodology18. (B) The amount of lipoprotein particles is expressed as the percentage of particles for every lipoprotein subclass with regard to the total number of particles. Row-wise normalized areas showed as mean±sem. VLDL: very low-density lipoprotein, lLDL: large low-density lipoprotein, sLDL: small low-density lipoprotein, lHDL: large high-density lipoprotein, mHDL: medium high-density lipoprotein, sHDL: small high-density lipoprotein
Mentions: Dyslipidemia is a risk factor linked to metabolic syndrome, T2D and CVD17. Here we studied the lipoprotein profile of HIAE girls beyond the standard measurement of cholesterol content of lipoproteins. By using an advanced lipoprotein analysis based on nuclear magnetic resonance (NMR) spectroscopy18, 1H-NMR allow to characterize the size and relative abundance of lipoprotein particles in serum. The use of NMR-derived lipoprotein subclasses improved cardiovascular risk stratification for subclinical atherosclerosis in comparison to conventional lipids19. Briefly, depending on the size of the lipoprotein particle, the methyl moieties of the lipids in lipoproteins resonate at slightly different frequencies, the smaller particles resonating at lower frequencies (Fig. 1a). Our NMR-derived lipoprotein subclasses were defined as VLDL, large LDL, small LDL, large HDL, medium HDL, and small HDL.

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