Abstract

Abstract Background: The plasma amino acid profile can be a useful indicator in clinical settings because it changes in response to various metabolic alternations. However, the association between the plasma amino acid profile and body fat accumulation has not been evaluated in humans. Objective: This study aimed to relate plasma amino acids to visceral fat accumulation in humans because excess visceral fat raises the odds ratio of developing metabolic syndrome. Design: A total of 1,449 subjects (985 males and 464 females) who had undergone a comprehensive health screening were enrolled in this study. The visceral fat area (VFA) was determined in each subject using CT imaging. Subjects were then divided into two groups according to VFA: high-VFA (&8805;100 cm2, n=867) and low-VFA (<100 cm2, n=582). The plasma amino acid profile was analyzed together with other metabolic valuables and then compared between the two groups using uni- and multivariate analyses. Results: As the degree of visceral fat accumulation increased, plasma concentrations of several amino acids changed significantly. Glu, Val, Leu, Ile, Tyr, Ala, Phe, Pro, Lys, Orn, Trp, Met, His and alpha-aminobutyric acid (ABA) levels were significantly higher in the high-VFA group compared to the low-VFA group, whereas the levels of Gly, Ser, Gln and Asn were significantly lower. To evaluate the potential of using amino acids as an indicator of VFA, a discriminant analysis was conducted with the multivariate logistic regression analysis "AminoIndex", and the ROC curve was calculated. The resulting "AminoIndex" exhibited an area under the ROC curve of 0.81 (95% confidence interval; 0.78 to 0.83), with higher sensitivity and specificity by 80% and 65%, respectively. Conclusions: The plasma amino acid profile changes depending on visceral fat content and can be used as a marker for diagnosing elevated visceral obesity in humans.

Highlights

  • Recent progress in metabolomics has enables the high throughput measurement of diverse amino acids 1-3 and has shown the new possibility of using amino acid analysis of biological samples as a biomarker discovery tool by generating diagnostic indices through systematic multivariate regression models[4]

  • Subjects were divided into two groups according to visceral fat area (VFA) volumes calculated from computed tomography (CT) images: highVFA (•100 cm[2], n=867) and low-VFA (

  • Body mass index (BMI), triglyceride levels, plasma glucose level, systolic blood pressure, diastolic blood pressure, hemoglobin A1c (HbA1c) and LDL cholesterol showed significant increases in the high-VFA group compared to the low-VFA group, with positive Pearson correlations with VFA value (n=1449)

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Summary

Introduction

Recent progress in metabolomics has enables the high throughput measurement of diverse amino acids 1-3 and has shown the new possibility of using amino acid analysis of biological samples as a biomarker discovery tool by generating diagnostic indices through systematic multivariate regression models[4]. Recent studies have suggested that there may be an association between plasma amino acid levels and obesity in both animals and humans. A reduction in the levels of Gly, Trp, Thr, His, taurine, citrulline and cystine has been reported in obese subjects[16] These studies strongly indicate that the volume of adipose tissue or its dysfunctions could affect amino acid metabolism and the levels of amino acids in peripheral circulation. The association between the plasma amino acid profile and body fat accumulation has not been evaluated in humans. To evaluate the potential of using amino acids as an indicator of VFA, a discriminant analysis was conducted with the multivariate logistic regression analysis “AminoIndex”, and the ROC curve was calculated. The resulting “AminoIndex” exhibited an area under the ROC curve of 0.81 (95% confidence interval; 0.78 to 0.83), with higher sensitivity and specificity by 80% and

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