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Cell Metab. 2019 Nov 5;30(5):963-975.e7. doi: 10.1016/j.cmet.2019.10.001. Epub 2019 Oct 24.

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

Author information

1
Department of Proteomics and Signal Transduction, Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany; The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark.
2
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark; The Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Copenhagen 2100, Denmark.
3
The Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, Department of Medicine, University of Toronto, Toronto, ON M5G 1X5, Canada.
4
The Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Copenhagen 2100, Denmark.
5
Department of Clinical Physiology, Nuclear Medicine and PET and Cluster for Molecular Imaging, Department of Biomedical Sciences, Rigshospitalet and University of Copenhagen, Copenhagen 2200, Denmark; Minerva Imaging ApS, Copenhagen 2200, Denmark.
6
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark.
7
Department of Proteomics and Signal Transduction, Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
8
Laboratory of Molecular Medicine, Department of Clinical Immunology, Rigshospitalet, University Hospital of Copenhagen, Copenhagen 2100, Denmark.
9
The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark.
10
Global Drug Discovery, Novo Nordisk A/S, Måløv 2760, Denmark.
11
Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark.
12
Department of Clinical Physiology, Nuclear Medicine and PET and Cluster for Molecular Imaging, Department of Biomedical Sciences, Rigshospitalet and University of Copenhagen, Copenhagen 2200, Denmark.
13
Princess Margaret Cancer Centre, Toronto, ON M5G 1L7, Canada.
14
Department of Proteomics and Signal Transduction, Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany; The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark. Electronic address: matthias.mann@cpr.ku.dk.
15
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark; The Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Copenhagen 2100, Denmark. Electronic address: cs@sund.ku.dk.

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.

KEYWORDS:

adipocyte complement factors; adipokines; brown fat commitment; brown fat differentiation; extracellular matrix proteins; human batokines; human brown adipocytes; human brown fat; mitochondria; secretomics

PMID:
31668873
DOI:
10.1016/j.cmet.2019.10.001

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