Retinoic acid has different effects on UCP1 expression in mouse and human adipocytes.
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.
Department of Biology, University of Copenhagen, Universitetsparken 13, DK-2100 Copenhagen Ø, Denmark. jacob.hansen@bio.ku.dk.
Maria
M
Murholm
Marie S
MS
Isidor
Astrid L
AL
Basse
Sally
S
Winther
Cathrine
C
Sørensen
Jonas
J
Skovgaard-Petersen
Maja M
MM
Nielsen
Aina S
AS
Hansen
Bjørn
B
Quistorff
Jacob B
JB
Hansen
D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D002454:Cell Differentiation; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D007473:Ion Channels / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D024101:Mitochondrial Proteins / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D047494:PPAR delta / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D061251:Primary Cell Culture; D018168:Receptors, Retinoic Acid / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D012176:Retinoids / Q000494:pharmacology; D015398:Signal Transduction; D013045:Species Specificity; D022722:Thermogenesis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism* / Q000494:pharmacology; D000071256:Uncoupling Protein 1
D001565:Benzoates; D007473:Ion Channels; D024101:Mitochondrial Proteins; D047494:PPAR delta; D047495:PPAR gamma; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D018168:Receptors, Retinoic Acid; D012176:Retinoids; D014157:Transcription Factors; C000604371:UCP1 protein, human; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D014212:Tretinoin; C038864:4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid