Dataset Information

Profiling of plasma metabolites in postmenopausal women with metabolic syndrome.

ABSTRACT:

Objective

The aim of the study was to investigate the associations of amino acids and other polar metabolites with metabolic syndrome (MetS) in postmenopausal women in a lean Asian population.

Methods

The participants were 1,422 female residents enrolled in a cohort study from April to August 2012. MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III modified for Japanese women. Associations were examined between MetS and 78 metabolites assayed in fasting plasma samples using capillary electrophoresis-mass spectrometry. Replication analysis was performed to confirm the robustness of the results in a separate population created by random allocation.

Results

Analysis was performed for 877 naturally postmenopausal women, including 594 in the original population and 283 in the replication population. The average age, body mass index, and levels of high- and low-density lipoprotein cholesterol of the entire population were 64.6 years, 23.0?kg/m, 72.1?mg/dL, and 126.1?mg/dL, respectively. There was no significant difference in low-density lipoprotein cholesterol levels between women with and without MetS. Thirteen metabolites were significantly related to MetS: multiple plasma amino acids were elevated in women with MetS, including branched-chain amino acids, alanine, glutamate, and proline; and alpha-aminoadipate, which is generated by lysine degradation, was also significantly increased.

Conclusions

Our large-scale metabolomic profiling indicates that Japanese postmenopausal women with MetS have abnormal polar metabolites, suggesting altered catabolic pathways. These results may help to understand metabolic disturbance, including in persons with normal body mass index and relatively high levels of high-density lipoprotein cholesterol, and may have clinical utility based on further studies.

SUBMITTER: Iida M

PROVIDER: S-EPMC4927224 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Publications

Profiling of plasma metabolites in postmenopausal women with metabolic syndrome.

Iida Miho M Harada Sei S Kurihara Ayako A Fukai Kota K Kuwabara Kazuyo K Sugiyama Daisuke D Takeuchi Ayano A Okamura Tomonori T Akiyama Miki M Nishiwaki Yuji Y Suzuki Asako A Hirayama Akiyoshi A Sugimoto Masahiro M Soga Tomoyoshi T Tomita Masaru M Banno Kouji K Aoki Daisuke D Takebayashi Toru T

Menopause (New York, N.Y.) 20160701 7

<h4>Objective</h4>The aim of the study was to investigate the associations of amino acids and other polar metabolites with metabolic syndrome (MetS) in postmenopausal women in a lean Asian population.<h4>Methods</h4>The participants were 1,422 female residents enrolled in a cohort study from April to August 2012. MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III modified for Japanese women. Associations were examined between MetS and 78 metabolite ...[more]

PMID: 27070805

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Project description:Background and purposeAtherosclerosis results from a maladaptive inflammatory response initiated by the intramural retention of LDL in susceptible areas of the arterial vasculature. The ω-3 polyunsaturated fatty acids (ω-3) have protective effects in atherosclerosis; however, their molecular mechanism is still largely unknown. The present study used a metabolomic approach to reveal the atheroprotective metabolites of ω-3 and investigate the underlying mechanisms.Experimental approachWe evaluated the development of atherosclerosis in LDL receptor-deficient mice (LDLR-/- ) fed a Western-type diet (WTD) plus ω-3 and also LDLR-/- and fat-1 transgenic (LDLR-/- -fat-1tg ) mice fed a WTD. The profiles of ω-3 in the plasma were screened by LC-MS/MS using unbiased systematic metabolomics analysis. We also studied the effect of metabolites of eicosapentaenoic acid (EPA) on endothelial activation in vitro.Key resultsThe ω-3 diet and fat-1 transgene decreased monocyte infiltration, inhibited the expression of pro-inflammatory genes and significantly attenuated atherosclerotic plaque formation and enhanced plaque stability in LDLR-/- mice. The content of 18-hydroxy-eicosapentaenoic acid (18-HEPE) and 17,18-epoxy-eicosatetraenoic acid (17,18-EEQ), from the cytochrome P450 pathway of EPA, was significantly higher in plasma from both ω-3-treated LDLR-/- and LDLR-/- -fat-1tg mice as compared with WTD-fed LDLR-/- mice. In vitro in endothelial cells, 18-HEPE or 17,18-EEQ decreased inflammatory gene expression induced by TNFα via NF-κB signalling and thereby inhibited monocyte adhesion to endothelial cells.Conclusions and implicationsEPA protected against the development of atherosclerosis in atheroprone mice via the metabolites 18-HEPE and/or 17,18-EEQ, which reduced endothelial activation. These compounds may have therapeutic implications in atherosclerosis.Linked articlesThis article is part of a themed section on Spotlight on Small Molecules in Cardiovascular Diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.8/issuetoc.

Dataset Information

Profiling of plasma metabolites in postmenopausal women with metabolic syndrome.

Objective

Methods

Results

Conclusions

Publications

Profiling of plasma metabolites in postmenopausal women with metabolic syndrome.

Similar Datasets

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