Early induction of pyruvate dehydrogenase kinase 4 by retinoic acids in adipocytes. Issue 5 (27th February 2017)

• Record Type: Journal Article
• Authors: Distel, Emilie; Cadoudal, Thomas; Collinet, Martine; Park, Edwards A.; Benelli, Chantal; Bortoli, Sylvie
• Is Part Of: Molecular nutrition & food research. Volume 61:Issue 5(2017)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-02-27
• Subjects: Adipose tissue -- Glyceroneogenesis -- Pyruvate dehydrogenase kinase 4 -- Retinoic acids; Food -- Biotechnology -- Periodicals; Food -- Microbiology -- Periodicals; Nutrition -- Periodicals; Food -- Toxicology -- Periodicals; Nutrition -- Periodicals; Food Microbiology -- Periodicals; Food Technology -- Periodicals; Molecular Biology -- Periodicals; 664.0705
• DOI: 10.1002/mnfr.201600920
• Languages: English
• ISSNs: 1613-4125

Abstract

Abstract : Adipocyte PDK4, by inhibiting PDH activity, is a key actor of fatty acid release via glyceroneogenesis. Here, we describe PDK4 as a new transcriptional target of RAs through two responsive elements (RAREa and RAREb). This regulation might participate to the reduced fatty acid release from the adipocyte and could play an important role in the development of metabolic diseases. 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.