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|Title:||Activated brown adipose tissue releases exosomes containing mitochondrial methylene tetrahydrofolate dehydrogenase (NADP dependent) 1-like protein (MTHFD1L)||Authors:||Leow, Melvin Khee-Shing
Verma, Sanjay K.
Thu, Giang Le Thi
Goh, Hui Jen
Sadananthan, Suresh Anand
Sze, Siu Kwan
Velan, S. Sendhil
|Issue Date:||2022||Source:||Leow, 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-. https://dx.doi.org/10.1042/BSR20212543||Project:||NMRC/CSA-INV/0003/2015||Journal:||Bioscience Reports||Abstract:||Brown 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.||URI:||https://hdl.handle.net/10356/162999||ISSN:||0144-8463||DOI:||10.1042/BSR20212543||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).||Fulltext Permission:||open||Fulltext Availability:||With Fulltext|
|Appears in Collections:||LKCMedicine Journal Articles|
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