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

Atul S Deshmukh, Lone Peijs, Jacqueline L Beaudry, Naja Z Jespersen, Carsten H Nielsen, Tao Ma, Andreas D Brunner, Therese J Larsen, Rafael Bayarri-Olmos, Bhargav S Prabhakar, Charlotte Helgstrand, Mai C K Severinsen, Birgitte Holst, Andreas Kjaer, Mads Tang-Christensen, Annika Sanfridson, Peter Garred, Gilbert G Privé, Bente K Pedersen, Zachary Gerhart-HinesSøren Nielsen, Daniel J Drucker, Matthias Mann, Camilla Scheele

Abstract

Adipokines secreted from white adipose tissue play a role in metabolic crosstalk and homeostasis, whereas the brown adipose secretome is less explored. We performed high-sensitivity mass-spectrometry-based proteomics on the cell media of human adipocytes derived from the supraclavicular brown adipose 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 brown and 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 thermogenic determination during adipogenesis. In conclusion, we report substantial differences between the secretomes of brown and white human adipocytes and identify novel candidate batokines that can be important regulators of human metabolism.

Original languageEnglish
JournalCell Metabolism
Volume30
Issue number5
Pages (from-to)963-975.e7
ISSN1550-4131
DOIs
Publication statusPublished - 5 Nov 2019

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