Clinical Studies and Practice

The metabolome profiling and pathway analysis in metabolic healthy and abnormal obesity

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Abstract

Objectives:

Mechanisms of the development of abnormal metabolic phenotypes among obese population are not yet clear. In this study, we aimed to screen metabolomes of both healthy and subjects with abnormal obesity to identify potential metabolic pathways that may regulate the different metabolic characteristics of obesity.

Methods:

We recruited subjects with body mass index (BMI) over 25 from the weight-loss clinic of a central hospital in Taiwan. Metabolic healthy obesity (MHO) is defined as without having any form of hyperglycemia, hypertension and dyslipidemia, while metabolic abnormal obesity (MAO) is defined as having one or more abnormal metabolic indexes. Serum-based metabolomic profiling using both liquid chromatography–mass spectrometry and gas chromatography–mass spectrometry of 34 MHO and MAO individuals with matching age, sex and BMI was performed. Conditional logistic regression and partial least squares discriminant analysis were applied to identify significant metabolites between the two groups. Pathway enrichment and topology analyses were conducted to evaluate the regulated pathways.

Results:

A differential metabolite panel was identified to be significantly differed in MHO and MAO groups, including L-kynurenine, glycerophosphocholine (GPC), glycerol 1-phosphate, glycolic acid, tagatose, methyl palmitate and uric acid. Moreover, several metabolic pathways were relevant in distinguishing MHO from MAO groups, including fatty acid biosynthesis, phenylalanine metabolism, propanoate metabolism, and valine, leucine and isoleucine degradation.

Conclusion:

Different metabolomic profiles and metabolic pathways are important for distinguishing between MHO and MAO groups. We have identified and discussed the key metabolites and pathways that may prove important in the regulation of metabolic traits among the obese, which could provide useful clues to study the underlying mechanisms of the development of abnormal metabolic phenotypes.

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Acknowledgements

This study was supported by grants NCKUH-9801002, NSC 99-2314-B-002-140-MY3 and 102-2314-B-002-117-MY3. We thank Ms. Yu-Chen Shih, Sheng-Chi Lee and Shih-Han Hsu at National Cheng Kung University for administrative assistance, data collection and sample preparation and experiments. We also thank Prof. Ching-hua Kuo, Mr. Wen-Hsin Huang, Han-Chun Kuo, Jiawei Liu and Cheng-En Tan at the Metabolomics Core Laboratory at the Center of Genomic Medicine of National Taiwan University for performing metabolomics experiments and analysis.

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Correspondence to C-H Wu or P-H Kuo.

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The authors declare no conflict of interest.

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Supplementary Information accompanies this paper on International Journal of Obesity website

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Chen, H., Tseng, Y., Wang, S. et al. The metabolome profiling and pathway analysis in metabolic healthy and abnormal obesity. Int J Obes 39, 1241–1248 (2015) doi:10.1038/ijo.2015.65

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