Norepinephrine triggers an immediate-early regulatory network response in primary human white adipocytes Higareda Almaraz, Juan Karbiener, Michael Giroud, Maude Pauler, Florian ; https://orcid.org/0000-0002-7462-0048 Gerhalter, Teresa Herzig, Stephan Scheideler, Marcel ddc:570 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. BioMed Central 2018 info:eu-repo/semantics/article doc-type:Article Article http://purl.org/coar/resource_type/c_2df8fbb1 https://research-explorer.ista.ac.at/record/20 https://research-explorer.ista.ac.at/download/20/5712 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> eng info:eu-repo/semantics/altIdentifier/doi/10.1186/s12864-018-5173-0 info:eu-repo/semantics/altIdentifier/issn/1471-2164 info:eu-repo/semantics/altIdentifier/wos/000450976700002 https://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess