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Vietor, I.* ; Cikes, D.* ; Piironen, K.* ; Vasakou, T.* ; Heimdörfer, D.* ; Gstir, R.* ; Erlacher, M.D.* ; Tancevski, I.* ; Eller, P.* ; Demetz, E.* ; Hess, M.W.* ; Kuhn, V.* ; Degenhart, G.* ; Rozman, J. ; Klingenspor, M.* ; Hrabě de Angelis, M. ; Valovka, T.* ; Huber, L.A.*

The negative adipogenesis regulator Dlk1 is transcriptionally regulated by Ifrd1 (TIS7) and translationally by its orthologue Ifrd2 (SKMc15).

eLife 12:e88350 (2023)
Publ. Version/Full Text DOI PMC
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Delta-like homolog 1 (Dlk1), an inhibitor of adipogenesis, controls the cell fate of adipocyte progenitors. Experimental data presented here identify two independent regulatory mechanisms, transcriptional and translational, by which Ifrd1 (TIS7) and its orthologue Ifrd2 (SKMc15) regulate Dlk1 levels. Mice deficient in both Ifrd1 and Ifrd2 (dKO) had severely reduced adipose tissue and were resistant to high-fat diet-induced obesity. Wnt signaling, a negative regulator of adipocyte differentiation, was significantly upregulated in dKO mice. Elevated levels of the Wnt/β-catenin target protein Dlk1 inhibited the expression of adipogenesis regulators Pparg and Cebpa, and fatty acid transporter Cd36. Although both Ifrd1 and Ifrd2 contributed to this phenotype, they utilized two different mechanisms. Ifrd1 acted by controlling Wnt signaling and thereby transcriptional regulation of Dlk1. On the other hand, distinctive experimental evidence showed that Ifrd2 acts as a general translational inhibitor significantly affecting Dlk1 protein levels. Novel mechanisms of Dlk1 regulation in adipocyte differentiation involving Ifrd1 and Ifrd2 are based on experimental data presented here.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Ifrd ; Adipocyte Differentiation ; Adipogenesis ; Cell Biology ; Diet-induced Obesity ; Lean Phenotype ; Mus Musculus ; Regulation ; Transcription ; Translation ; Translational Inhibition; Ppar-gamma; Adipose-tissue; Adipocyte Differentiation; Cd36 Deficiency; Gene-expression; Messenger-rnas; Fatty-acids; Mice; Preadipocyte; Inhibition
Language english
Publication Year 2023
HGF-reported in Year 2023
ISSN (print) / ISBN 2050-084X
e-ISSN 2050-084X
Journal eLife
Quellenangaben Volume: 12, Issue: , Pages: , Article Number: e88350 Supplement: ,
Publisher eLife Sciences Publications
Publishing Place Sheraton House, Castle Park, Cambridge, Cb3 0ax, England
Reviewing status Peer reviewed
Institute(s) Institute of Experimental Genetics (IEG)
POF-Topic(s) 30201 - Metabolic Health
Research field(s) Genetics and Epidemiology
PSP Element(s) G-500692-001
G-500600-001
Grants Austrian FWF grant agency
Austrian Science Fund
DOI 10.7554/eLife.88350
WOS ID 001122033400001
Scopus ID 85169180016
PubMed ID 37603466
Erfassungsdatum 2023-10-06
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