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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

Proposed mechanism to explain the long-term health risks of hyperinsulinaemic androgen excess.Schematic representation of the underlying pathway by which HIAE is associated with long-term health risks, namely metabolic syndrome, diabetes and cardiovascular disease.
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f6: Proposed mechanism to explain the long-term health risks of hyperinsulinaemic androgen excess.Schematic representation of the underlying pathway by which HIAE is associated with long-term health risks, namely metabolic syndrome, diabetes and cardiovascular disease.

Mentions: Recently, Lee et al demonstrated that low sugar consumption is associated with increasing HDL levels in females during adolescence47. In addition, excessive sugar intake in combination with hyperandrogenism causes oxidative stress484950. In this context, we postulate that the current period of caloric abundance and chronically positive energy balance for most adolescents51, induces oxidation of lipoprotein particles and impaired lipoprotein function. Our data and those of others5253, indicate that alterations in lipoprotein metabolism precede impaired fasting glycemia, impaired glucose tolerance and hypertriglyceridemia (Fig. 6). This suggests that the triad of methionine sulfoxide in serum, size of HDL particles and the ratio of methionine oxidation in apo-A1 may potentially become a novel biomarker of pre-diabetes and metabolic syndrome. Further work is needed to study this combination of biomarkers in the general population.


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)

Proposed mechanism to explain the long-term health risks of hyperinsulinaemic androgen excess.Schematic representation of the underlying pathway by which HIAE is associated with long-term health risks, namely metabolic syndrome, diabetes and cardiovascular disease.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f6: Proposed mechanism to explain the long-term health risks of hyperinsulinaemic androgen excess.Schematic representation of the underlying pathway by which HIAE is associated with long-term health risks, namely metabolic syndrome, diabetes and cardiovascular disease.
Mentions: Recently, Lee et al demonstrated that low sugar consumption is associated with increasing HDL levels in females during adolescence47. In addition, excessive sugar intake in combination with hyperandrogenism causes oxidative stress484950. In this context, we postulate that the current period of caloric abundance and chronically positive energy balance for most adolescents51, induces oxidation of lipoprotein particles and impaired lipoprotein function. Our data and those of others5253, indicate that alterations in lipoprotein metabolism precede impaired fasting glycemia, impaired glucose tolerance and hypertriglyceridemia (Fig. 6). This suggests that the triad of methionine sulfoxide in serum, size of HDL particles and the ratio of methionine oxidation in apo-A1 may potentially become a novel biomarker of pre-diabetes and metabolic syndrome. Further work is needed to study this combination of biomarkers in the general population.

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