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Metabolomics of Dynamic Changes in Insulin Resistance Before and After Exercise in PCOS.

ABSTRACT: Background: Plasma elevated levels of branched chain amino acids (BCAA) and aromatic amino acids (AAA) have been associated with obesity and insulin resistance, but their relationship to stimulated insulin resistance (IR) in PCOS and in response to exercise is unknown. Indeed, it is unknown whether the mechanism of IR in PCOS is mediated through changes in the metabolome. Methods: Twelve women with polycystic ovary syndrome (PCOS) and ten age and body mass index matched controls completed an 8 week supervised exercise program at 60% maximal oxygen consumption. Before and after the exercise program, all participants underwent maximal IR stimulation with intralipid infusions followed by insulin sensitivity (IS) measurement by hyperinsulinaemic euglycaemic clamps. Amino acid profiles and metabolites were taken at baseline and at maximal insulin resistance stimulation before and after the exercise program. Results: At baseline, PCOS subjects showed increased leucine/isoleucine, glutamate, methionine, ornithine, phenylalanine, tyrosine and proline (p < 0.05) that, following exercise, did not differ from controls. While compering within the groups, no significant changes in the amino acid levels before and after exercise were observed. Exercise improved VO2 max (p < 0.01) but did not alter weight. Amino acid profiles were unaffected by an acute increase in IR induced by the lipid infusion. IS was lower in PCOS (p < 0.001) and was further decreased by the lipid infusion in both PCOS and controls. Although, exercise improved IS in both PCOS and in controls, the IS remained compromised in PCOS. Conclusion: The baseline amino acid profile in PCOS reflected that seen in obese subjects and differed to controls. After exercise, and despite no change in weight in either group, there were no differences in the amino acid profile between PCOS and controls. This shows that exercise may normalize the amino acid metabolome, irrespective of weight. ISRCTN number: ISRCTN42448814.

SUBMITTER: Halama A

PROVIDER: S-EPMC6400834 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Metabolomics of Dynamic Changes in Insulin Resistance Before and After Exercise in PCOS.

Halama Anna A Aye Myint Myint MM Dargham Soha R SR Kulinski Michal M Suhre Karsten K Atkin Stephen L SL

Frontiers in endocrinology 20190227

<b>Background:</b> Plasma elevated levels of branched chain amino acids (BCAA) and aromatic amino acids (AAA) have been associated with obesity and insulin resistance, but their relationship to stimulated insulin resistance (IR) in PCOS and in response to exercise is unknown. Indeed, it is unknown whether the mechanism of IR in PCOS is mediated through changes in the metabolome. <b>Methods:</b> Twelve women with polycystic ovary syndrome (PCOS) and ten age and body mass index matched controls co ...[more]

PMID: 30873121

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Project description:Background and objectivePolycystic ovary syndrome (PCOS) is a complex metabolic disorder associated with ovulatory dysfunction, hyperandrogenism, obesity, and insulin resistance, which leads to subfertility. PCOS is the most frequent metabolic disorder in women and the major cause of infertility. Susceptibility to developing PCOS is determined by a complex interaction between environmental and genetic factors. Although different mechanisms have been proposed to explain PCOS manifestations, defects in insulin actions or in the insulin signaling pathways are central in the pathogenesis of the syndrome. However, the mechanisms (molecular players and signaling pathways) underlying its primary origin still remain an unsolved issue. Current research is increasingly focusing on the discovery of novel biomarkers to further elucidate the complex pathophysiology of PCOS. Sam68, an RNA-binding protein, is recruited to insulin signaling, mediating different insulin actions. We aimed to investigate the role of Sam68 in insulin signaling and the possible implications of Sam68 in the insulin resistance in PCOS.Materials and methodsGranulosa cells were taken from women with PCOS (n = 25) and healthy donors (n = 25) and, within the age range of 20 to 42 years, from GINEMED, Assisted Reproduction Centre, Seville, Spain. The Sam68 expression level was analyzed both by qPCR and immunoblot. Statistical significance was assessed by one-way ANOVA, followed by a post-hoc test. A p value of < 0.05 was considered statistically significant.ResultsWe found that insulin stimulation increases the phosphorylation and expression level of Sam68 in granulosa cells from normal donors. The downregulation of Sam68 expression resulted in a lower activation of both the MAPK and the PI3K pathways in response to insulin. Moreover, the granulosa cells from the women with PCOS presented a lower expression of Sam68, as well as insulin receptor and insulin receptor substrate-1 (IRS-1). In these cells, the overexpression of Sam68 resulted in an increased activation of both the MAPK and the PI3K pathways in response to insulin.ConclusionsThese results suggest the participation of Sam68 in insulin receptor signaling, mediating the insulin effect in granulosa cells, and they suggest the possible role of Sam68 in the insulin resistance of PCOS.

Dataset Information

Metabolomics of Dynamic Changes in Insulin Resistance Before and After Exercise in PCOS.

Publications

Metabolomics of Dynamic Changes in Insulin Resistance Before and After Exercise in PCOS.

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