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Open Access Research article

Retinoic acid has different effects on UCP1 expression in mouse and human adipocytes

Maria Murholm12, Marie S Isidor12, Astrid L Basse12, Sally Winther1, Cathrine Sørensen1, Jonas Skovgaard-Petersen1, Maja M Nielsen1, Aina S Hansen1, Bjørn Quistorff2 and Jacob B Hansen1*

Author Affiliations

1 Department of Biology, University of Copenhagen, Universitetsparken 13, DK-2100 Copenhagen Ø, Denmark

2 Department of Biomedical Sciences, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark

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BMC Cell Biology 2013, 14:41  doi:10.1186/1471-2121-14-41

Published: 23 September 2013

Abstract

Background

Increased adipose thermogenesis is being considered as a strategy aimed at preventing or reversing obesity. Thus, regulation of the uncoupling protein 1 (UCP1) gene in human adipocytes is of significant interest. Retinoic acid (RA), the carboxylic acid form of vitamin A, displays agonist activity toward several nuclear hormone receptors, including RA receptors (RARs) and peroxisome proliferator-activated receptor δ (PPARδ). Moreover, RA is a potent positive regulator of UCP1 expression in mouse adipocytes.

Results

The effects of all-trans RA (ATRA) on UCP1 gene expression in models of mouse and human adipocyte differentiation were investigated. ATRA induced UCP1 expression in all mouse white and brown adipocytes, but inhibited or had no effect on UCP1 expression in human adipocyte cell lines and primary human white adipocytes. Experiments with various RAR agonists and a RAR antagonist in mouse cells demonstrated that the stimulatory effect of ATRA on UCP1 gene expression was indeed mediated by RARs. Consistently, a PPARδ agonist was without effect. Moreover, the ATRA-mediated induction of UCP1 expression in mouse adipocytes was independent of PPARγ coactivator-1α.

Conclusions

UCP1 expression is differently affected by ATRA in mouse and human adipocytes. ATRA induces UCP1 expression in mouse adipocytes through activation of RARs, whereas expression of UCP1 in human adipocytes is not increased by exposure to ATRA.

Keywords:
Adipogenesis; ATRA; Brown adipocyte; UCP1; White adipocyte