Activated brown adipose tissue releases exosomes containing mitochondrial methylene tetrahydrofolate dehydrogenase (NADP dependent) 1-like protein (MTHFD1L)

Activated brown adipose tissue releases exosomes containing mitochondrial methylene tetrahydrofolate dehydrogenase (NADP dependent) 1-like protein (MTHFD1L)

Bioscience Reports

10.1042/BSR20212543

https://doi.org/10.1042/bsr20212543

Melvin Khee-Shing Leow, Anantharaj Rengaraj, Kothandaraman Narasimhan, Sanjay K. Verma, Jadegoud Yaligar, Giang Le Thi Thu, Lijuan Sun, Hui Jen Goh, Priya Govindharajulu, Suresh Anand Sadananthan, Navin Michael, Wei Meng, Xavier Gallart-Palau, Lei Sun, Neerja Karnani, Newman Siu Kwan Sze, S. Sendhil Velan

03 May 2022

Leow, M. K.-S., 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, N. 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). https://doi.org/10.1042/bsr20212543

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.

Attribution 4.0 International (CC BY 4.0)

This research / project is supported by the Singapore Ministry of Health’s National Medical Research Council (NMRC) - National Medical Research Council (NMRC) Clinician Scientist Award
Grant Reference no. : NMRC/CSA-INV/0003/2015

https://oar.a-star.edu.sg/communities-collections/articles/21864

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