Proteomics-based comparative mapping of the human brown and white adipocyte secretome reveals EPDR1 as a novel batokine

Abstract

Secreted proteins from adipose tissue play a role in metabolic cross-talk and homeostasis. We performed high sensitivity mass spectrometry-based proteomics on the cell media of in vitro differentiated, non-immortalized brown adipocytes derived from supraclavicular adipose of adult humans and white adipocytes derived from subcutaneous adipose of adult humans. We identified 471 potentially secreted proteins covering interesting protein categories such as hormones, growth factors, growth factor binding proteins, cytokines, extracellular matrix proteins, and proteins of the complement system, which were differentially regulated in brown and white adipocytes. A total of 101 proteins were exclusively quantified in brown adipocytes, among these ependymin-related protein 1 (EPDR1). Ablation of EPDR1 impaired the induction of thermogenic transcripts in response to norepinephrine in brown adipocytes, while EPDR1-treated mice increased their energy consumption, suggesting a role in brown fat commitment and activation. Our work reveals substantial differences between the secretomes of brown and white human adipocytes and identifies novel candidate batokines.the degradation of the alternative C3 convertase (C3bBb). In addition, CFH acts as a cofactor to 20045).Ollikainen, M., 2017. Subcutaneous adipose tissue gene expression and DNA methylation respond to both short-and long-term weight loss. Int. J. Obes. 1-12.

New insights into the secretory functions of brown adipose tissue

“…Recently, Deshmukh et al (2018) have reported a proteomics-based analysis of the brown adipocyte proteome from human brown adipocytes in response to noradrenaline. ECM components, complement factors and several other proteins reported to be a part of the thermogenically stimulated mouse brown adipocyte secretome were also found in the noradrenaline-stimulated human brown adipocyte secretome (e.g., fibrillin-1, SPARC-like protein 1, progranulin, and transforming growth factor-β receptor-3).…”

Genetic background and diet affect brown adipose gene co-expression – metabolic associations

“…Mice lacking brown adipose tissue develop obesity and metabolic dysfunction [29] that is independent from the loss of thermogenic UCP1 activity [21,30,31], indicating that brown adipose contributes to healthy metabolism through thermogenesis-independent mechanisms. Several studies have sought to identify potential metabolically-relevant brown adipose cytokines, or “batokines” underlying these mechanisms [32–34]. However, very little research has focused on understanding the potential regulation of these batokines, and most studies regarding transcriptional networks in brown adipose tissue have focused exclusively on identifying regulators and effectors of nonshivering thermogenesis and brown adipocyte identity [35,36,45–49,37–44].…”