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Gene Review

Dlk1  -  delta-like 1 homolog (Drosophila)

Rattus norvegicus

Synonyms: Pref-1, Zog
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Disease relevance of Dlk1

  • We found that Pref-1 was synthesized in normal islets and in RINm5F insulinoma cells and released into the medium in two forms, of which one corresponded to FA1 [1].

High impact information on Dlk1

  • This transformation of adipocytes from cells that store triglycerides to fatty acid-oxidizing cells is accompanied by loss of the adipocyte markers, adipocyte fatty acid-binding protein 2, tumor necrosis factor alpha, and leptin, and by the appearance of the preadipocyte marker Pref-1 [2].
  • The reduction of the adipocyte markers caused by bezafibrate was accompanied by an increase in the mRNA levels of the preadipocyte marker Pref-1 (1.6-fold induction; P < 0.01) [3].
  • Similarly, fatty acid translocase (2.6-fold induction; P = 0.002) and Pref-1 (5.6-fold induction) mRNA levels increased, although differences in the latter were not significant because of huge individual variations [3].
  • The expression of preadipocyte factor-1/fetal antigen 1 was decreased during differentiation, and GH treatment prevented this down-regulation of Pref1/FA1 [4].
  • The level of Pref-1 message in the adrenal glands of animals having various pituitary-adrenal axis activities, as well as various plasma salt concentrations, correlated with the total number of glomerulosa cells [5].

Biological context of Dlk1

  • These findings suggest that the capsular cells, mostly composed of the glomerulosa cells, may have potential for differentiating into other zones' cells, and the down-regulation of Pref-1 expression may be an important step in the adrenal zonal differentiation [5].

Anatomical context of Dlk1

  • We recently reported that ZOG, a rat homolog of Pref-1, was specifically expressed in the adrenal zona glomerulosa [6].
  • First we studied the biosynthesis and processing of Pref-1 to the soluble form, FA1, in pancreatic islets and insulinoma cells transfected with Pref-1 cDNA [1].
  • This element would function as the promoter of the Pref-1 gene in H295R cells, but not in HeLa cells [6].
  • Results of the investigation of Pref-1 expression in preadipocyte and in undifferentiated adrenal cortex suggested that down-regulation of Pref-1 gene was closely correlated with the differentiation process [6].
  • Between well- and poorly compensated rats, significant differences on expression level were found for Yy1 (liver), Ppargamma (heart), Nfkappab (bone), Pref-1 (spleen), and Lepr (thymus, liver, heart) [7].

Associations of Dlk1 with chemical compounds


Other interactions of Dlk1

  • These results indicate that Pref-1/FA1 is not mediating the mitogenic effect of GH and PRL [1].
  • Mutations of four or five nucleotides in a 7-nucleotides-stretch in the midst of the Egr/GC-box eliminated the binding of Sp1/3, abolished the activation by Egr-factor(s) and diminished the Pref-1 promoter activity [6].

Analytical, diagnostic and therapeutic context of Dlk1

  • The experimental treatment resulted in a decrease and increase in Pref-1 expression in ACTH treated and low sodium diet treated rats respectively, in accordance with changes in abundance of glomerulosa cells [8].


  1. Expression, biosynthesis and release of preadipocyte factor-1/ delta-like protein/fetal antigen-1 in pancreatic beta-cells: possible physiological implications. Friedrichsen, B.N., Carlsson, C., Møldrup, A., Michelsen, B., Jensen, C.H., Teisner, B., Nielsen, J.H. J. Endocrinol. (2003) [Pubmed]
  2. Reversing adipocyte differentiation: implications for treatment of obesity. Zhou, Y.T., Wang, Z.W., Higa, M., Newgard, C.B., Unger, R.H. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  3. Bezafibrate reduces mRNA levels of adipocyte markers and increases fatty acid oxidation in primary culture of adipocytes. Cabrero A, n.u.l.l., Alegret, M., Sánchez, R.M., Adzet, T., Laguna, J.C., Vázquez, M. Diabetes (2001) [Pubmed]
  4. Characterization of the inhibitory effect of growth hormone on primary preadipocyte differentiation. Hansen, L.H., Madsen, B., Teisner, B., Nielsen, J.H., Billestrup, N. Mol. Endocrinol. (1998) [Pubmed]
  5. Cloning of a membrane-spanning protein with epidermal growth factor-like repeat motifs from adrenal glomerulosa cells. Halder, S.K., Takemori, H., Hatano, O., Nonaka, Y., Wada, A., Okamoto, M. Endocrinology (1998) [Pubmed]
  6. Characterization of a proximal element in the rat preadipocyte factor-1 (Pref-1) gene promoter. Takemori, H., Doi, J., Katoh, Y., Halder, S.K., Lin, X.Z., Horike, N., Hatano, O., Okamoto, M. Eur. J. Biochem. (2001) [Pubmed]
  7. Diabetes per se and metabolic state influence gene expression in tissue-dependent manner of BB/OK rats. Klöting, N., Follak, N., Klöting, I. Diabetes Metab. Res. Rev. (2005) [Pubmed]
  8. Pref-1, SF-1 and adrenocortical zonation. Raza, F.S., Puddefoot, J.R., Vinson, G.P. Endocr. Res. (1998) [Pubmed]
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