Retinoic acid administration and vitamin A status modulate retinoid X receptor alpha and retinoic acid receptor alpha levels in mouse brown adipose tissue.

BACKGROUND/AIMS: 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.

CONCLUSION: RA modulates the expression of cognate receptors in BAT, suggesting auto regulation of the retinoid effect on the thermogenic system.