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-Hines; Søren Nielsen; Daniel J Drucker; Matthias Mann; Camilla Scheele

doi:10.1016/j.cmet.2019.10.001

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^*

^*Corresponding author for this work

31 Citations (Scopus)

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 language	English
Journal	Cell Metabolism
Volume	30
Issue number	5
Pages (from-to)	963-975.e7
Number of pages	21
ISSN	1550-4131
DOIs	https://doi.org/10.1016/j.cmet.2019.10.001
Publication status	Published - 5 Nov 2019

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Deshmukh, A. S., Peijs, L., Beaudry, J. L., Jespersen, N. Z., Nielsen, C. H., Ma, T., Brunner, A. D., Larsen, T. J., Bayarri-Olmos, R., Prabhakar, B. S., Helgstrand, C., Severinsen, M. C. K., Holst, B., Kjaer, A., Tang-Christensen, M., Sanfridson, A., Garred, P., Privé, G. G., Pedersen, B. K., ... Scheele, C. (2019). Proteomics-Based Comparative Mapping of the Secretomes of Human Brown and White Adipocytes Reveals EPDR1 as a Novel Batokine. Cell Metabolism, 30(5), 963-975.e7. https://doi.org/10.1016/j.cmet.2019.10.001

Deshmukh, AS, Peijs, L, Beaudry, JL, Jespersen, NZ, Nielsen, CH, Ma, T, Brunner, AD, Larsen, TJ, Bayarri-Olmos, R, Prabhakar, BS, Helgstrand, C, Severinsen, MCK, Holst, B , Kjaer, A, Tang-Christensen, M, Sanfridson, A, Garred, P, Privé, GG, Pedersen, BK, Gerhart-Hines, Z, Nielsen, S, Drucker, DJ, Mann, M & Scheele, C 2019, 'Proteomics-Based Comparative Mapping of the Secretomes of Human Brown and White Adipocytes Reveals EPDR1 as a Novel Batokine', Cell Metabolism, vol. 30, no. 5, pp. 963-975.e7. https://doi.org/10.1016/j.cmet.2019.10.001

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

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.",

author = "Deshmukh, {Atul S} and Lone Peijs and Beaudry, {Jacqueline L} and Jespersen, {Naja Z} and Nielsen, {Carsten H} and Tao Ma and Brunner, {Andreas D} and Larsen, {Therese J.} and Rafael Bayarri-Olmos and Prabhakar, {Bhargav S} and Charlotte Helgstrand and Severinsen, {Mai C K} and Birgitte Holst and Andreas Kjaer and Mads Tang-Christensen and Annika Sanfridson and Peter Garred and Priv{\'e}, {Gilbert G} and Pedersen, {Bente K} and Zachary Gerhart-Hines and S{\o}ren Nielsen and Drucker, {Daniel J} and Matthias Mann and Camilla Scheele",

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AU - Deshmukh, Atul S

AU - Peijs, Lone

AU - Beaudry, Jacqueline L

AU - Jespersen, Naja Z

AU - Nielsen, Carsten H

AU - Ma, Tao

AU - Brunner, Andreas D

AU - Larsen, Therese J.

AU - Bayarri-Olmos, Rafael

AU - Prabhakar, Bhargav S

AU - Helgstrand, Charlotte

AU - Severinsen, Mai C K

AU - Holst, Birgitte

AU - Kjaer, Andreas

AU - Tang-Christensen, Mads

AU - Sanfridson, Annika

AU - Garred, Peter

AU - Privé, Gilbert G

AU - Pedersen, Bente K

AU - Gerhart-Hines, Zachary

AU - Nielsen, Søren

AU - Drucker, Daniel J

AU - Mann, Matthias

AU - Scheele, Camilla

PY - 2019/11/5

Y1 - 2019/11/5

N2 - 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.

AB - 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.

U2 - 10.1016/j.cmet.2019.10.001

DO - 10.1016/j.cmet.2019.10.001

M3 - Journal article

C2 - 31668873

SN - 1550-4131

VL - 30

SP - 963-975.e7

JO - Cell Metabolism

JF - Cell Metabolism

IS - 5

ER -

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

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