Norepinephrine triggers an immediate-early regulatory network response in primary human white adipocytes Journal Article


Author(s): Higareda-Almaraz, Juan C; Karbiener, Michael; Giroud, Maude; Pauler, Florian M; Gerhalter, Teresa; Herzig, Stephan; Scheideler, Marcel
Article Title: Norepinephrine triggers an immediate-early regulatory network response in primary human white adipocytes
Affiliation IST Austria
Abstract: 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.
Keywords: Early cell fate; Immediate-early gene; Network biology; Norepinephrine stimulation; Transcriptional regulatory network; White adipocyte
Journal Title: BMC Genomics
Volume: 19
Issue 1
ISSN: 14712164
Publisher: BioMed Central  
Date Published: 2018-11-03
Start Page: article number: 794
Copyright Statement: CC BY 4.0
Sponsor: This work was funded by the German Centre for Diabetes Research (DZD) and the Austrian Science Fund (FWF, P25729-B19).
DOI: 10.1186/s12864-018-5173-0
Open access: yes (OA journal)