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Identification of Ganglioside GM3 Molecular Species in Human Serum Associated with Risk Factors of Metabolic Syndrome.

ABSTRACT: Serum GM3 molecular species were quantified in 125 Japanese residents using tandem mass spectrometry multiple reaction monitoring. Individuals were categorized by the presence or absence of metabolic disease risk factors including visceral fat accumulation, hyperglycemia and dyslipidemia. A total of 23 GM3 molecular species were measured, of these, eight were found to be significantly elevated in individuals with visceral fat accumulation and metabolic disease, defined as the presence of hyperglycemia and dyslipidemia. All of the GM3 molecular species were composed of the sphingoid base sphingosine (d18:1 (Δ4)) and, interestingly, six of the eight elevated GM3 molecular species contained a hydroxylated ceramide moiety. The hydroxylated GM3 species were, in order of decreasing abundance, d18:1-h24:0 ≈ d18:1-h24:1 > d18:1-h22:0 » d18:1-h20:0 > d18:1-h21:0 > d18:1-h18:1. Univariate and multiple linear regression analyses were conducted using a number of clinical health variables associated with obesity, type 2 diabetes, metabolic disease, atherosclerosis and hypertension. GM3(d18:1-h24:1) was identified as the best candidate for metabolic screening, proving to be significantly correlated with intima-media thickness, used for the detection of atherosclerotic disease in humans, and a number of metabolic disease risk factors including autotaxin, LDL-c and homeostatic model assessment insulin resistance (HOMA-IR).

SUBMITTER: Veillon L

PROVIDER: S-EPMC4477979 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Low concentrations of serum 25-hydroxyvitamin D [25(OH)D] may be associated with cardiometabolic disorders; however, little is known about their relation to intermediate metabolic and lipid markers.We investigated the relation of serum 25(OH)D concentrations to fasting insulin, glucose, dyslipidemia, adiposity, and prevalent metabolic syndrome.We conducted this cross-sectional analysis in 292 postmenopausal women aged 50-79 y in the Women's Health Initiative Calcium-Vitamin D (WHI-CaD) trial. Data were collected from 3 nested case-control studies that measured baseline serum 25(OH)D concentrations. Inverse probability weighting was used to approximate parameter estimates for the WHI-CaD population.In weighted linear regression models adjusted for age, race-ethnicity, month of blood draw, region, case-control status, smoking, alcohol, physical activity, and history of cardiometabolic risk factors, there was an inverse association of serum 25(OH)D with adiposity [body mass index (BMI): ? = -1.12 ± 0.30, P = 0.0002; waist circumference: ? = -3.57 ± 0.49, P < 0.0001; waist-hip ratio: ? = -0.01 ± 0.002, P < 0.0001], triglycerides (? = -0.10 ± 0.02, P < 0.0001), and triglyceride:HDL-cholesterol ratio (? = -0.11 ± 0.03, P = 0.0003). The multivariable-adjusted odds ratio for metabolic syndrome for the highest (?52 nmol/L) compared with the lowest (<35 nmol/L) tertile of serum 25(OH)D concentrations was 0.28 (95% CI: 0.14, 0.56). Significant associations remained after adjustment for BMI. We observed no significant associations with LDL cholesterol, HDL cholesterol, insulin, glucose, homeostatic model assessment of insulin resistance (HOMA-IR), or homeostatic model assessment of ? cell function (HOMA-?).Higher serum 25(OH)D concentrations may be inversely associated with adiposity, triglycerides, triglyceride:HDL-cholesterol ratio, and metabolic syndrome but are not associated with LDL and HDL cholesterol, insulin, glucose, HOMA-IR, or HOMA-? in postmenopausal women. This trial was registered at clinicaltrials.gov as NCT00000611.

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Identification of Ganglioside GM3 Molecular Species in Human Serum Associated with Risk Factors of Metabolic Syndrome.

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