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Higareda-Almaraz, J. ; Karbiener, M.* ; Giroud, M. ; Pauler, F.M.* ; Gerhalter, T.* ; Herzig, S. ; Scheideler, M.

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

BMC Genomics 19:794 (2018)

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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.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Norepinephrine Stimulation ; White Adipocyte ; Early Cell Fate ; Network Biology ; Immediate-early Gene ; Transcriptional Regulatory Network; Brown Adipose-tissue; Mesenchymal Stem-cells; Adipogenic Differentiation; Induced Thermogenesis; Gene-expression; Activation; Pathways; Fat; Growth; Distinct

ISSN (print) / ISBN 1471-2164

e-ISSN 1471-2164

Journal BMC Genomics

Quellenangaben Volume: 19, Issue: 1, Article Number: 794

Publisher BioMed Central

Publishing Place Campus, 4 Crinan St, London N1 9xw, England

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Diabetes and Cancer (IDC)