Abstract
Background: The secretory properties of brown adipose tissue are thought to contribute to the association between active brown fat and a healthy metabolic status. Although a few brown adipokines have been identified, a comprehensive knowledge of the brown adipose tissue secretome is lacking.Methods: Here, to examine the effects of thermogenic activation of brown adipocytes on protein secretion, we used isobaric tags for relative and absolute quantification (iTRAQ) analysis to determine how the secreted proteome of brown adipocytes (that detected in cell culture medium) differed in response to cAMP.Results: Our results indicated that 56 secreted proteins were up-regulated in response to cAMP. Of them, nearly half (29) corresponded to extracellular matrix components and regulators. Several previously known adipokines, were also detected. Unexpectedly, we also found five components of the complement system. Only 15 secreted proteins were down-regulated by cAMP; of them three were ECM-related and none was related to the complement system. We observed a partial concordance between the cAMP-regulated release of proteins (both from proteomics and from antibody-based quantification of specific proteins) and the cAMP-mediated regulation of their encoding transcript for the up-regulated secreted proteins. However, a stronger concordance was seen for the down-regulated secreted proteins.Conclusions: The present results highlight the need to investigate previously unrecognized processes such as the role of extracellular matrix in thermogenic activation-triggered brown fat remodeling, as well as the intriguing question of how brown adipocyte-secreted complement factors contribute to the signaling properties of active brown adipose tissue.
Highlights
The high capacity of brown adipose tissue (BAT) for energy expenditure and oxidation of glucose and lipids is associated with protection against obesity, hyperglycemia and hyperlipidemia in rodents and possibly in humans (Bartelt et al, 2011; Giralt and Villarroya, 2017; Carobbio et al, 2018)
Murine C57BAT brown pre-adipocytes were supplied by Klein et al (1999) and were obtained using protocols approved by the Institutional Animal Care and Use Committee, Joslin Diabetes Center (Boston, USA)
Differentiation and Effects of cAMP in Brown Adipocytes Cultured in Serum-Free Medium
Summary
The high capacity of brown adipose tissue (BAT) for energy expenditure and oxidation of glucose and lipids is associated with protection against obesity, hyperglycemia and hyperlipidemia in rodents and possibly in humans (Bartelt et al, 2011; Giralt and Villarroya, 2017; Carobbio et al, 2018). Most brown adipokines were identified from the high-level expression of genes encoding putative secreted proteins, such as fibroblast growth factor-21 (FGF21) or interleukin-6 (IL-6) in active BAT (Burýsek and Houstek, 1997; Hondares et al, 2011). Brown adipokine candidates were identified by screening transcriptomic data from BAT using bioinformatic tools that can predict the “secretability” of encoded factors (Wang et al, 2014; Verdeguer et al, 2015; Cereijo et al, 2018). We still lack a comprehensive knowledge of the BAT secretome. The secretory properties of brown adipose tissue are thought to contribute to the association between active brown fat and a healthy metabolic status. A few brown adipokines have been identified, a comprehensive knowledge of the brown adipose tissue secretome is lacking
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