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The negative adipogenesis regulator Dlk1 is transcriptionally regulated by Ifrd1 (TIS7) and translationally by its orthologue Ifrd2 (SKMc15).
eLife 12:e88350 (2023)
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
ISSN (print) / ISBN
2050-084X
e-ISSN
2050-084X
Journal
eLife
Quellenangaben
Volume: 12,
Article Number: e88350
Publisher
eLife Sciences Publications
Publishing Place
Sheraton House, Castle Park, Cambridge, Cb3 0ax, England
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Experimental Genetics (IEG)
Grants
Austrian FWF grant agency
Austrian Science Fund
Austrian Science Fund