Serum metabolic profiles in overweight and obese women with and without metabolic syndrome

Abstract

Objective: To identify serum biomarkers through metabolomics approach that distinguishes physically inactive overweight/obese women with metabolic syndrome from those who are metabolically healthy, independent of body weight and fat mass.

Methods: We applied nuclear magnetic resonance spectroscopy-based profiling of fasting serum samples to examine the metabolic differences between 78 previously physically inactive, body weight and fat mass matched overweight/obese premenopausal women with and without MetS. MetS was defined as the presence of at least three of the following five criteria: waist circumference ≥88 cm, serum triacylglycerol ≥1.7 mmol/L, and high density lipoprotein cholesterol (HDL-C) <1.30 mmol/L, blood pressure ≥ 130/85 mmHg and fasting glucose ≥5.6 mmol/L). Principal component analysis was used to reduce the large number of correlated variables to fewer uncorrelated factors.

Results: Two metabolic factors were associated with MetS independent of BMI, fat mass, waist circumference and physical activity/fitness. Factor comprising branched-chain amino acids (BCAA) and aromatic amino acids (AAA) and orosomucoid was associated with all clinical risk factors (p < 0.01 for all).

Conclusion: Two metabolic factors distinguish overweight/obese women with metabolic syndrome from those who are metabolically healthy independent of body weight, fat mass and physical activity/fitness. In particular, factor comprising BCAA, AAA and orosomucoid seems auspicious biomarker determining metabolic health as it was associated with all clinical risk factors. Further research is needed to determine the public health and clinical significance of these results in terms of screening to identify those at greatest cardio-metabolic risk for whom appropriate intervention strategies should be developed.

Figures

Figure 1

Hierarchical clustering of metabolomics data values in MHO and MetS groups. The heat map shows changes of x-fold standard deviation from the overall mean concentration of the metabolite in each individual belonging to either MHO or MetS group. Green squares represent a decrease, and red squares an increase. Metabolite names are shown on x-axis and individual subjects with adherent groups on (right) y-axis.

Figure 2

A pruned visualization of the correlation network from un-adjusted Spearman correlation analysis. Each variable was converted to a surrogate linear predictor before computations. The color of the edges indicate the association magnitude as shown in the legend. The vertices are colored as red and blue if all edges of the vertex are positive or negative correlations, respectively. In the cases where the vertex has both negative and positive correlations with its neighbor, the vertex is colored orange. Abbreviations: SBP = systolic blood pressure; DBP = diastolic blood pressure; VLDL = triacylglycerol and cholesterol in very-low density lipoprotein particles; LDL = triacylglycerol and cholesterol in low density lipoprotein particles; IDL = triacylglycerol and cholesterol in intermediate-density lipoprotein particles; Factor 1 (leucine, isoleucine, valine, tyrosine, phenylalanine, orosomucoid); Factor 2 (total fatty acids, omega-6 fatty acids, omega7 and 9 fatty acids, linoleic acid, mono-unsaturated fatty acids, total phosphoglycerides, total phosphocholines); Factor 3 (docosahexaenoic acid, polyunsaturated fatty acids, omega-3 fatty acids); Factor 5 (glutamine, glycine, pyruvate); Factor 6 (acetate, histidine); Factor 7 (creatinine, citrate); Factor 8 (urea).