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dc.contributor.authorLeow, Melvin Khee-Shingen_US
dc.contributor.authorRengaraj, Anantharajen_US
dc.contributor.authorNarasimhan, Kothandaramanen_US
dc.contributor.authorVerma, Sanjay K.en_US
dc.contributor.authorYaligar, Jadegouden_US
dc.contributor.authorThu, Giang Le Thien_US
dc.contributor.authorSun, Lijuanen_US
dc.contributor.authorGoh, Hui Jenen_US
dc.contributor.authorGovindharajulu, Priyaen_US
dc.contributor.authorSadananthan, Suresh Ananden_US
dc.contributor.authorMichael, Navinen_US
dc.contributor.authorMeng, Weien_US
dc.contributor.authorGallart-Palau, Xavieren_US
dc.contributor.authorSun, Leien_US
dc.contributor.authorKarnani, Neerjaen_US
dc.contributor.authorSze, Siu Kwanen_US
dc.contributor.authorVelan, S. Sendhilen_US
dc.identifier.citationLeow, M. K., Rengaraj, A., Narasimhan, K., Verma, S. K., Yaligar, J., Thu, G. L. T., Sun, L., Goh, H. J., Govindharajulu, P., Sadananthan, S. A., Michael, N., Meng, W., Gallart-Palau, X., Sun, L., Karnani, N., Sze, S. K. & Velan, S. S. (2022). Activated brown adipose tissue releases exosomes containing mitochondrial methylene tetrahydrofolate dehydrogenase (NADP dependent) 1-like protein (MTHFD1L). Bioscience Reports, 42(5), 20212543-.
dc.description.abstractBrown adipose tissue (BAT) is a promising weapon to combat obesity and metabolic disease. BAT is thermogenic and consumes substantial amounts of glucose and fatty acids as fuel for thermogenesis and energy expenditure. To study BAT function in large human longitudinal cohorts, safe and precise detection methodologies are needed. Although regarded a gold standard, the foray of PET-CT into BAT research and clinical applications is limited by its high ionizing radiation doses. Here, we show that brown adipocytes release exosomes in blood plasma that can be utilized to assess BAT activity. In the present study, we investigated circulating protein biomarkers that can accurately and reliably reflect BAT activation triggered by cold exposure, capsinoids ingestion and thyroid hormone excess in humans. We discovered an exosomal protein, methylene tetrahydrofolate dehydrogenase (NADP+ dependent) 1-like (MTHFD1L), to be overexpressed and detectable in plasma for all three modes of BAT activation in human subjects. This mitochondrial protein is packaged as a cargo within multivesicular bodies of the endosomal compartment and secreted as exosomes via exocytosis from activated brown adipocytes into the circulation. To support MTHFD1L as a conserved BAT activation response in other vertebrates, we examined a rodent model and also proved its presence in blood of rats following BAT activation by cold exposure. Plasma concentration of exosomal MTHFD1L correlated with human BAT activity as confirmed by PET-MR in humans and supported by data from rats. Thus, we deduce that MTHFD1L appears to be overexpressed in activated BAT compared to BAT in the basal nonstimulated state.en_US
dc.description.sponsorshipAgency for Science, Technology and Research (A*STAR)en_US
dc.description.sponsorshipMinistry of Health (MOH)en_US
dc.description.sponsorshipNational Medical Research Council (NMRC)en_US
dc.relation.ispartofBioscience Reportsen_US
dc.rights© 2022 The Author(s). This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY).en_US
dc.subjectScience::Biological sciencesen_US
dc.titleActivated brown adipose tissue releases exosomes containing mitochondrial methylene tetrahydrofolate dehydrogenase (NADP dependent) 1-like protein (MTHFD1L)en_US
dc.typeJournal Articleen
dc.contributor.schoolLee Kong Chian School of Medicine (LKCMedicine)en_US
dc.contributor.schoolSchool of Biological Sciencesen_US
dc.contributor.organizationSingapore Institute for Clinical Sciences, A*STARen_US
dc.contributor.organizationDuke-NUS Medical Schoolen_US
dc.contributor.organizationYong Loo Lin School of Medicine, NUSen_US
dc.contributor.organizationTan Tock Seng Hospitalen_US
dc.description.versionPublished versionen_US
dc.subject.keywordsMitochondrial Proteinen_US
dc.subject.keywordsBrown Adipose Tissueen_US
dc.description.acknowledgementThe study was funded by the Singapore Ministry of Health’s National Medical Research Council (NMRC) Clinician Scientist Award [grant number NMRC/CSA-INV/0003/2015] awarded to A/Prof. MKSL and also partly supported by the Agency for Science, Technology and Research (A*STAR).en_US
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