Abstract
The adipose organ, including white and brown adipose tissues, is an important player in systemic energy homeostasis, storing excess energy in form of lipids while releasing energy upon various energy demands. Recent studies have demonstrated that white and brown adipocytes also function as endocrine cells and regulate systemic metabolism by secreting factors that act locally and systemically. However, a comparative proteomic analysis of secreted factors from white and brown adipocytes and their responsiveness to adrenergic stimulation has not been reported yet. Therefore, we studied and compared the secretome of white and brown adipocytes, with and without norepinephrine (NE) stimulation. Our results reveal that carbohydrate-metabolism-regulating proteins are preferably secreted from white adipocytes, while brown adipocytes predominantly secrete a large variety of proteins. Upon NE stimulation, an increased secretion of known adipokines is favored by white adipocytes while brown adipocytes secreted higher amounts of novel adipokines. Furthermore, the secretory response between NE-stimulated and basal state was multifaceted addressing lipid and glucose metabolism, adipogenesis, and antioxidative reactions. Intriguingly, NE stimulation drastically changed the secretome in brown adipocytes. In conclusion, our study provides a comprehensive catalogue of novel adipokine candidates secreted from white and brown adipocytes with many of them responsive to NE. Given the beneficial effects of brown adipose tissue activation on its endocrine function and systemic metabolism, this study provides an archive of novel batokine candidates and biomarkers for activated brown adipose tissue.
Highlights
The adipose organ, including white and brown adipose tissues, is an important player in systemic energy homeostasis, storing excess energy in form of lipids while releasing energy upon various energy demands
In this study, we investigated the secretome of stroma-vascular fraction (SVF)-derived murine white and brown adipocytes by using mass spectrometry combined with click-chemistry and pulsed stable isotope labeling with amino acids in cell culture
Spondin-1showed a fivefold increased secretion in white adipocytes and was the highest differentially secreted protein from white adipocytes. It was first identified as adipokine secreted from white adipocytes in rats, and its secretion was shown to be regulated by insulin resistance [19]
Summary
The secretome of white and brown primary murine adipocytes, with and without stimulation with norepinephrine (NE), has been determined by using mass spectrometry combined with AHA labeling and pulsed SILAC. Mice completely lacking BAT became obese while mice only deficient in UCP1 became cold sensitive but not obese [9, 10] These studies suggest that BAT can affect whole-body energy homeostasis by UCP1-dependent and independent mechanisms involving “brown adipokines” or “batokines.” recent studies in mice and rats have identified the first brown adipokine candidates with autocrine, paracrine, and endocrine functions, including vascular endothelial growth factor-A, insulin-like growth factor I (IGF-I), fibroblast growth factor-2, fibroblast growth factor-21, neuregulin 4, triiodothyronine, interleukin 6, and bone morphogenetic protein 8b [11]. Our study provides a comprehensive insight into the secretome of white and brown adipocytes with numerous novel adipokine candidates, in part responsive to NE
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