PuSH - Publication Server of Helmholtz Zentrum München: Fibroblast growth factor induced Ucp1 expression in preadipocytes requires PGE2 biosynthesis and glycolytic flux.

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Gantert, T.* ; Henkel, F. ; Wurmser, C.* ; Oeckl, J.* ; Fischer, L.* ; Haid, M. ; Adamski, J. ; Esser-von Bieren, J. ; Klingenspor, M.* ; Fromme, T.*

Fibroblast growth factor induced Ucp1 expression in preadipocytes requires PGE2 biosynthesis and glycolytic flux.

FASEB J. 35:e21572 (2021)

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High uncoupling protein 1 (Ucp1) expression is a characteristic of differentiated brown adipocytes and is linked to adipogenic differentiation. Paracrine fibroblast growth factor 8b (FGF8b) strongly induces Ucp1 transcription in white adipocytes independent of adipogenesis. Here, we report that FGF8b and other paracrine FGFs act on brown and white preadipocytes to upregulate Ucp1 expression via a FGFR1-MEK1/2-ERK1/2 axis, independent of adipogenesis. Transcriptomic analysis revealed an upregulation of prostaglandin biosynthesis and glycolysis upon Fgf8b treatment of preadipocytes. Oxylipin measurement by LC-MS/MS in FGF8b conditioned media identified prostaglandin E₂ as a putative mediator of FGF8b induced Ucp1 transcription. RNA interference and pharmacological inhibition of the prostaglandin E₂ biosynthetic pathway confirmed that PGE2 is causally involved in the control over Ucp1 transcription. Importantly, impairment of or failure to induce glycolytic flux blunted the induction of Ucp1, even in the presence of PGE₂ . Lastly, a screening of transcription factors identified Nrf1 and Hes1 as required regulators of FGF8b induced Ucp1 expression. Thus, we conclude that paracrine FGFs co-regulate prostaglandin and glucose metabolism to induce Ucp1 expression in a Nrf1/Hes1-dependent manner in preadipocytes, revealing a novel regulatory network in control of Ucp1 expression in a formerly unrecognized cell type.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Fgf Signaling ; Fgf8 ; Pge2 ; Ucp1 ; Glucose Metabolism ; Glycolysis ; Paracrine Fibroblast Growth Factor ; Preadipocyte ; Prostaglandin ; Uncoupling Protein 1; Brown Adipose-tissue; Fat; Mouse; Fgf21; Mice; Evolution; Roles; Cell

ISSN (print) / ISBN 0892-6638

e-ISSN 1530-6860

Journal FASEB Journal

Quellenangaben Volume: 35, Issue: 5, Article Number: e21572

Publisher Wiley

Publishing Place Bethesda, Md.

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute for Allergy Research (IAF)
Molekulare Endokrinologie und Metabolismus (MEM)
Institute of Experimental Genetics (IEG)

Grants German Research Foundation