Retinoic acid has different effects on UCP1 expression in mouse and human adipocytesReport as inadecuate

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BMC Cell Biology

, 14:41

Cell differentiation and proliferation


BackgroundIncreased 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.

ResultsThe 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.

ConclusionsUCP1 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.

KeywordsAdipogenesis ATRA Brown adipocyte UCP1 White adipocyte AbbreviationsADRPAdipose differentiation-related protein

ATRAAll-trans RA

BATBrown adipose tissue

COUP-TFIIChicken ovalbumin upstream promoter transcription factor II

DMEMDulbecco’s Modified Eagle’s Medium

FABP4Fatty acid-binding protein 4

FBSFoetal bovine serum

GAPDHGlyceraldehyde 3-phosphate dehydrogenase

HPrADPrimary human white preadipocytes-adipocytes


MAPKMitogen activated protein kinase

MEFMouse embryo fibroblast

PGC-1αPPARγ coactivator-1α

PPARPeroxisome proliferator-activated receptor

RARetinoic acid

RARRA receptor

RbRetinoblastoma gene

RT-qPCRReverse transcription-quantitative polymerase chain reaction


TBPTATA-binding protein

TR4Testicular orphan receptor 4

UCP1Uncoupling protein 1

WATWhite adipose tissue


Electronic supplementary materialThe online version of this article doi:10.1186-1471-2121-14-41 contains supplementary material, which is available to authorized users.

Maria Murholm, Marie S Isidor contributed equally to this work.

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