Proteomics-Based Comparative Mapping of the Secretomes of Human Brown and White Adipocytes Reveals EPDR1 as a Novel Batokine

Summary Adipokinessecreted from white adipose tissueplay a role in metabolic crosstalk and homeostasis, whereas the brownadipose secretomeis less explored. We performed high-sensitivity mass-spectrometry-based proteomics on the cell media of human adipocytesderived from the supraclavicular brownadipose and from the subcutaneous white adipose depots of adult humans. We identified 471 potentially secreted proteins covering interesting categories such as hormones, growth factors, extracellular matrix proteins, and proteins of the complement system, which were differentially regulated between brownand white adipocytes. A total of 101 proteins were exclusively quantified in brown adipocytes, and among these was ependymin-related protein 1 (EPDR1). EPDR1 was detected in human plasma, and functional studies suggested a role for EPDR1 in thermogenicdetermination during adipogenesis. In conclusion, we report substantial differences between the secretomesof brownand white human adipocytesand identify novel candidate batokines that can be important regulators of human metabolism.