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

Elife. 2023 Aug 21:12:e88350. doi: 10.7554/eLife.88350.


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.

Keywords: IFRD; adipocyte differentiation; adipogenesis; cell biology; diet-induced obesity; lean phenotype; mus musculus; regulation; transcription; translation; translational inhibition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes
  • Adipogenesis* / genetics
  • Adipose Tissue
  • Animals
  • CD36 Antigens
  • Calcium-Binding Proteins* / genetics
  • Cell Differentiation
  • Immediate-Early Proteins*
  • Membrane Proteins* / genetics
  • Mice


  • Calcium-Binding Proteins
  • CD36 Antigens
  • Dlk1 protein, mouse
  • Ifrd1 protein, mouse
  • Immediate-Early Proteins
  • Membrane Proteins
  • Ifrd2 protein, mouse