MSACL 2019 EU Abstract

Targeted Metabolomics Reveals an Influence of the FTO Gene on the Kynurenine Pathway

La-or Chailurkit(1), Nichawat Paiyabhroma(1), Suwannee Chanprasertyothin(2), Nisakorn Thongmung(2), Piyamitr Sritara(1), Boonsong Ongphiphadhanakul(1).
(1)Department of Medicine and (2)Office of Research, Academic Affairs and Innovations, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

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La-or Chailurkit (Presenter) Mahidol University >> POSTER (PDF)

Presenter Bio: Name : La-or Chailurkit

Address : Division of Endocrinology and Metabolism,
Department of Medicine, Faculty of Medicine,
Ramathibodi Hospital, Bangkok 10400, Thailand.

Present position : Medical Technologist, Advisory Level

Education :Doctor of Health Science, Graduate School of Medicine, The University of Tokyo, Japan.

Publications: 138 publications (20 of them are using LC-MS/MS method)

Relevant Financial Disclosures (within past 24 months) No relevant financial relationship(s) to disclose. Conflict mitigation NOT REQUIRED.

INTRODUCTION: Genome wide association studies have identified the FTO gene as the first susceptibility gene of obesity. Previous studies have suggested a role of FTO in nucleic acid repair or modification, but how this leads to an alteration in energy homeostasis is unclear. In the present study, we utilized targeted metabolomics in an attempt to further elucidate mechanisms underlying the action of the FTO gene.

METHODS: This study was part of a health survey of employees of the Electricity Generating Authority of Thailand (n = 79 , 9 female and 70 male). Targeted metabolomics analysis was performed using the AbsoluteIDQ™ p180 kit combined with flow injection analysis and liquid chromatography tandem mass spectrometry. Genotyping of the FTO rs9939609 was performed using real-time PCR (TaqMan® MGB probes).
RESULTS: Using OPLS-DA, there was no apparent clustering of the metabolites in relation to the FTO genotype. Nevertheless, using variable importance on projection to identify metabolites with higher influence on potential clustering, it was found that tryptophan was among the metabolites within the 10 highest VIP scores. We therefore further examined the influence of the FTO gene on the major pathway of tryptophan catabolism, the kynurenine pathway. Pearson’s correlation analysis showed that kynurenine and tryptophan was positively correlated only in subjects with the rs9939609 G allele (n = 32, r = 0.56, p < 0.001) and the correlation coefficients were significantly higher in subjects having the G allele compared to those subjects without the G allele (P < 0.05). Moreover, kynurenine/trytophan ratio, a biomarker of the degree of tryptophan to kynurenine conversion, was significantly associated with the presence of the G allele independent of body mass index and gender.

CONCLUSION: FTO gene influences the conversion of tryptophan to kynurenine. Alternation in the kynurenine pathway may be one of the mechanism underlying the action of FTO in the pathogenesis of obesity and its related effects.