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

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Proteomics-Based Comparative Mapping of the Secretomes of Human Brown and White Adipocytes Reveals EPDR1 as a Novel Batokine.
Cell Metabolism ( IF 27.7 ) Pub Date : 2019-10-24 , DOI: 10.1016/j.cmet.2019.10.001
Atul S Deshmukh ₁ , Lone Peijs ₂ , Jacqueline L Beaudry ₃ , Naja Z Jespersen ₄ , Carsten H Nielsen ₅ , Tao Ma ₆ , Andreas D Brunner ₇ , Therese J Larsen ₄ , Rafael Bayarri-Olmos ₈ , Bhargav S Prabhakar ₉ , Charlotte Helgstrand ₁₀ , Mai C K Severinsen ₄ , Birgitte Holst ₁₁ , Andreas Kjaer ₁₂ , Mads Tang-Christensen ₁₀ , Annika Sanfridson ₁₀ , Peter Garred ₈ , Gilbert G Privé ₁₃ , Bente K Pedersen ₄ , Zachary Gerhart-Hines ₆ , Søren Nielsen ₄ , Daniel J Drucker ₃ , Matthias Mann ₁₄ , Camilla Scheele ₂

Affiliation

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.
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.
The Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, Department of Medicine, University of Toronto, Toronto, ON M5G 1X5, Canada.
The Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Copenhagen 2100, Denmark.
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.
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark.
Department of Proteomics and Signal Transduction, Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
Laboratory of Molecular Medicine, Department of Clinical Immunology, Rigshospitalet, University Hospital of Copenhagen, Copenhagen 2100, Denmark.
The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark.
Global Drug Discovery, Novo Nordisk A/S, Måløv 2760, Denmark.
Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark.
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.
Princess Margaret Cancer Centre, Toronto, ON M5G 1L7, Canada.
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.

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.

中文翻译：

基于蛋白质组学的人类棕色和白色脂肪细胞分泌组的比较图谱揭示了EPDR1作为一种新型Batokine。

白色脂肪组织分泌的脂肪因子在代谢串扰和体内平衡中起着作用，而棕色脂肪分泌物的探索则较少。我们对源自成年人的锁骨上褐色脂肪和皮下白色脂肪库的人类脂肪细胞的细胞培养基进行了基于高灵敏度质谱的蛋白质组学研究。我们鉴定了471种潜在分泌的蛋白，涵盖了有趣的类别，例如激素，生长因子，细胞外基质蛋白和补体系统的蛋白，这些蛋白在棕色和白色脂肪细胞之间受到差异调节。共有101种蛋白质专门在棕色脂肪细胞中进行了定量，其中有Ependymin相关蛋白1（EPDR1）。在人体血浆中检测到EPDR1，功能研究表明，EPDR1在脂肪形成过程中的产热测定中起着重要作用。总之，我们报道了棕色和白色人类脂肪细胞分泌组之间的实质性差异，并确定了可能是人类新陈代谢的重要调节剂的新型候选Batokines。

更新日期：2019-11-09

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