TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000404938
  • Gene Name:ABCB5
  • mRNA database:Ensembl
  • mRNA expression :up-regulated
  • mRNA Method:PCR
  • mRNA Pathway:NA
  • Evidence:validated
  • (mRNA-drug)

Drug basic information

  • Drug ID:NA
  • Drug Name:Retinoic acids
  • Drug Method:up-regulated the gene expression

Disease basic infommation

  • Disease:metabolic disease
  • Tissue:patients tissues

Other information

  • Title:Early induction of pyruvate dehydrogenase kinase 4 by retinoic acids in adipocytes
  • Journal:Molecular Nutrition & Food Research
  • Published:2017
  • PubMed ID:27981737
  • Abstract:Scope:Vitamin A and its metabolites, such as retinoic acids (RA), are related to metabolic diseases, in particular insulin resistance and obesity. Here, we studied the roles of 9-cis RA and all-trans RA on the regulation of pyruvate dehydrogenase kinase 4 (PDK4), an enzyme involved in fatty acid reesterification, which is a crucial metabolic pathway in adipose tissue (AT) lipid homeostasis. Methods and results:9-cis RA and all-trans RA treatment of human and murine AT explants, as well as adipocytes (3T3-F442A cell line) induces PDK4 expression both at the mRNA and the protein level, via a transcriptional mechanism. Using site-directed mutagenesis and chomatin immuno-precipitation, we showed that this activation involves two new RA responsive elements in the Pdk4 promoter, RAREa (DR1: -125/-112) and RAREb (DR1: -86/-73), specific to AT. Furthermore, even though endogeneous Pdk4 gene was upregulated by RA in Fao cells, a rat hepatoma cell line, the induction did not occur through the newly found RAREs. Conclusion:In this study, we showed that adipocyte PDK4 gene is a new target of the vitamin A derived RA and might participate to the reduced fatty acid efflux from the adipocyte, a step that plays an important role in the developement of metabolic diseases.
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