Early induction of pyruvate dehydrogenase kinase 4 by retinoic acids in adipocytes

Emilie Distel, Thomas Cadoudal, Martine Collinet, Edwards Park, Chantal Benelli, Sylvie Bortoli

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish (US)
Article number1600920
JournalMolecular Nutrition and Food Research
Volume61
Issue number5
DOIs
StatePublished - May 1 2017

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pyruvate dehydrogenase (acetyl-transferring) kinase
retinoic acid
Tretinoin
adipocytes
Adipocytes
Adipose Tissue
Metabolic Diseases
adipose tissue
Vitamin A
metabolic diseases
Fatty Acids
vitamin A
Cell Line
3T3 Cells
cell lines
Site-Directed Mutagenesis
Metabolic Networks and Pathways
fatty acids
Genes
Insulin Resistance

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Food Science

Cite this

Early induction of pyruvate dehydrogenase kinase 4 by retinoic acids in adipocytes. / Distel, Emilie; Cadoudal, Thomas; Collinet, Martine; Park, Edwards; Benelli, Chantal; Bortoli, Sylvie.

In: Molecular Nutrition and Food Research, Vol. 61, No. 5, 1600920, 01.05.2017.

Research output: Contribution to journalArticle

Distel, Emilie ; Cadoudal, Thomas ; Collinet, Martine ; Park, Edwards ; Benelli, Chantal ; Bortoli, Sylvie. / Early induction of pyruvate dehydrogenase kinase 4 by retinoic acids in adipocytes. In: Molecular Nutrition and Food Research. 2017 ; Vol. 61, No. 5.
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