Retinoic acid administration and vitamin A status modulate retinoid X receptor alpha and retinoic acid receptor alpha levels in mouse brown adipose tissue.
OBJECTIVE
Retinoic acid (RA), the carboxylic acid form of vitamin A, through the activation of cognate receptors, stimulates the transcription of the gene encoding uncoupling protein 1 (UCP1), which is critical to brown adipose tissue (BAT) thermogenesis. RA was previously shown to down-regulate the steady state levels of retinoic acid receptor alpha (RARalpha) and retinoid X receptor alpha (RXRalpha) in primary brown adipocytes differentiated in culture. Our aim was to study the impact of RA-treatment and vitamin A status on the expression levels of these receptors in vivo.


METHODS
Three-week-old mice were fed standard chow or a vitamin A deficient diet for 10 weeks, after which animals on both diets were treated with all-trans RA (ATRA, 100 mg x Kg(-1) day(-1)) or vehicle during 4 days. Levels of UCP1, RARalpha and RXRalpha in BAT were determined by immunoblotting.


RESULTS
ATRA-treatment resulted in a reduction of the specific RARalpha and especially RXRalpha content in BAT that paralleled the induction of UCP1 appearance in the tissue. RARalpha and RXRalpha levels per gram of BAT were reduced in mice chronically fed the vitamin A-deficient diet.


CONCLUSIONS
RA modulates the expression of cognate receptors in BAT, suggesting auto regulation of the retinoid effect on the thermogenic system.
Ribot
Joan
J
Laboratory of Molecular Biology, Nutrition and Biotechnology, Department of Fundamental Biology and Health Sciences, University of the Balearic Islands, 07122 Palma de Mallorca, Spain.
Felipe
Francisco
F
Bonet
M Luisa
ML
Palou
Andreu
A
D017667:Adipocytes / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002352:Carrier Proteins / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects; D004032:Diet; D005786:Gene Expression Regulation / Q000187:drug effects; D007473:Ion Channels; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis; D051379:Mice; D024101:Mitochondrial Proteins; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D000072482:Retinoic Acid Receptor alpha; D047490:Retinoid X Receptor alpha / Q000378:metabolism*; D022722:Thermogenesis / Q000187:drug effects; D014212:Tretinoin / Q000008:administration & dosage*; D000071256:Uncoupling Protein 1; D014801:Vitamin A / Q000008:administration & dosage*
D000970:Antineoplastic Agents; D002352:Carrier Proteins; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C000607072:Rara protein, mouse; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D047490:Retinoid X Receptor alpha; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D014801:Vitamin A; D014212:Tretinoin