article published yes Juan Higareda Almaraz author Michael Karbiener author Maude Giroud author Florian Pauler author 48EA0138-F248-11E8-B48F-1D18A9856A870000-0002-7462-0048 Teresa Gerhalter author Stephan Herzig author Marcel Scheideler author SiHi department Background: Norepinephrine (NE) signaling has a key role in white adipose tissue (WAT) functions, including lipolysis, free fatty acid liberation and, under certain conditions, conversion of white into brite (brown-in-white) adipocytes. However, acute effects of NE stimulation have not been described at the transcriptional network level. Results: We used RNA-seq to uncover a broad transcriptional response. The inference of protein-protein and protein-DNA interaction networks allowed us to identify a set of immediate-early genes (IEGs) with high betweenness, validating our approach and suggesting a hierarchical control of transcriptional regulation. In addition, we identified a transcriptional regulatory network with IEGs as master regulators, including HSF1 and NFIL3 as novel NE-induced IEG candidates. Moreover, a functional enrichment analysis and gene clustering into functional modules suggest a crosstalk between metabolic, signaling, and immune responses. Conclusions: Altogether, our network biology approach explores for the first time the immediate-early systems level response of human adipocytes to acute sympathetic activation, thereby providing a first network basis of early cell fate programs and crosstalks between metabolic and transcriptional networks required for proper WAT function. https://research-explorer.ista.ac.at/download/20/5712/2018_BMCGenomics_Higareda.pdf application/pdfno BioMed Central2018 eng 1471-2164 00045097670000210.1186/s12864-018-5173-0 191 https://research-explorer.ista.ac.at/record/9807 https://research-explorer.ista.ac.at/record/9808 Higareda Almaraz J, Karbiener M, Giroud M, Pauler F, Gerhalter T, Herzig S, Scheideler M. 2018. Norepinephrine triggers an immediate-early regulatory network response in primary human white adipocytes. BMC Genomics. 19(1). Higareda Almaraz, Juan, et al. “Norepinephrine Triggers an Immediate-Early Regulatory Network Response in Primary Human White Adipocytes.” <i>BMC Genomics</i>, vol. 19, no. 1, BioMed Central, 2018, doi:<a href="https://doi.org/10.1186/s12864-018-5173-0">10.1186/s12864-018-5173-0</a>. Higareda Almaraz J, Karbiener M, Giroud M, et al. Norepinephrine triggers an immediate-early regulatory network response in primary human white adipocytes. <i>BMC Genomics</i>. 2018;19(1). doi:<a href="https://doi.org/10.1186/s12864-018-5173-0">10.1186/s12864-018-5173-0</a> J. Higareda Almaraz, M. Karbiener, M. Giroud, F. Pauler, T. Gerhalter, S. Herzig, M. Scheideler, BMC Genomics 19 (2018). Higareda Almaraz, Juan, Michael Karbiener, Maude Giroud, Florian Pauler, Teresa Gerhalter, Stephan Herzig, and Marcel Scheideler. “Norepinephrine Triggers an Immediate-Early Regulatory Network Response in Primary Human White Adipocytes.” <i>BMC Genomics</i>. BioMed Central, 2018. <a href="https://doi.org/10.1186/s12864-018-5173-0">https://doi.org/10.1186/s12864-018-5173-0</a>. J. Higareda Almaraz <i>et al.</i>, “Norepinephrine triggers an immediate-early regulatory network response in primary human white adipocytes,” <i>BMC Genomics</i>, vol. 19, no. 1. BioMed Central, 2018. Higareda Almaraz, J., Karbiener, M., Giroud, M., Pauler, F., Gerhalter, T., Herzig, S., &#38; Scheideler, M. (2018). Norepinephrine triggers an immediate-early regulatory network response in primary human white adipocytes. <i>BMC Genomics</i>. BioMed Central. <a href="https://doi.org/10.1186/s12864-018-5173-0">https://doi.org/10.1186/s12864-018-5173-0</a> 202018-12-11T11:44:12Z2023-09-13T09:10:47Z