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BMC Genomics. 2018 Nov 3;19(1):794. doi: 10.1186/s12864-018-5173-0.

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

Higareda-Almaraz JC1,2,3,4,5, Karbiener M6, Giroud M7,8,9,10, Pauler FM11,12, Gerhalter T12, Herzig S7,8,9,10, Scheideler M13,14,15,16,17.

Author information

1
Institute for Diabetes and Cancer (IDC), Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany. juan.higareda@helmholtz-muenchen.de.
2
Joint Heidelberg-IDC Translational Diabetes Program, Heidelberg University Hospital, Heidelberg, Germany. juan.higareda@helmholtz-muenchen.de.
3
Molecular Metabolic Control, Medical Faculty, Technical University, Munich, Germany. juan.higareda@helmholtz-muenchen.de.
4
German Center for Diabetes Research (DZD), Neuherberg, Germany. juan.higareda@helmholtz-muenchen.de.
5
NMR laboratory, Institute of Myology, Hopital Universitaire Pitie Salpetriere, Paris, France. juan.higareda@helmholtz-muenchen.de.
6
Department of Phoniatrics, ENT University Hospital, Medical University of Graz, Graz, Austria.
7
Institute for Diabetes and Cancer (IDC), Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
8
Joint Heidelberg-IDC Translational Diabetes Program, Heidelberg University Hospital, Heidelberg, Germany.
9
Molecular Metabolic Control, Medical Faculty, Technical University, Munich, Germany.
10
German Center for Diabetes Research (DZD), Neuherberg, Germany.
11
CeMM, Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
12
Present Address: Institute of Science and Technology (IST) Austria, Klosterneuburg, Austria.
13
Institute for Diabetes and Cancer (IDC), Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany. marcel.scheideler@helmholtz-muenchen.de.
14
Joint Heidelberg-IDC Translational Diabetes Program, Heidelberg University Hospital, Heidelberg, Germany. marcel.scheideler@helmholtz-muenchen.de.
15
Molecular Metabolic Control, Medical Faculty, Technical University, Munich, Germany. marcel.scheideler@helmholtz-muenchen.de.
16
German Center for Diabetes Research (DZD), Neuherberg, Germany. marcel.scheideler@helmholtz-muenchen.de.
17
NMR laboratory, Institute of Myology, Hopital Universitaire Pitie Salpetriere, Paris, France. marcel.scheideler@helmholtz-muenchen.de.

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

PMID:
30390616
PMCID:
PMC6215669
DOI:
10.1186/s12864-018-5173-0
[Indexed for MEDLINE]
Free PMC Article

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