DIFFERENTIAL-EFFECTS OF RETINOIC ACID ON UNCOUPLING PROTEIN-1 AND LEPTIN GENE-EXPRESSION

All-trans-retinoic acid (RA), one of the active metabolites of vitamin A, can increase the expression of uncoupling protein-1 (UCP1) gene. T o determine whether RA stimulates brown adipose tissue (BAT) thermogen esis and modulates leptin gene expression in vivo, 6-month-old, vitami n-A sufficient, F344 x BN rats were administered a single dose of RA ( 7.5 mg/kg, i.p.) or the beta(3)-adrenergic receptor (beta(3)AR) specif ic agonist, CGP 12177 (0.75 mg/kg). Levels of UCP1 mRNA in BAT and lep tin mRNA in perirenal white adipose tissue (WAT) were examined 5h afte r treatment, mRNA levels of lipoprotein lipase (LPL) were also examine d in BAT and perirenal WAT. Administration of CGP 12177 caused the exp ected increase in UCP1 mRNA levels. RA treatment also significantly in creased UCP1 mRNA levels but to a lesser extent than CGP 12177, In con trast, there was no acute effect of RA on whole body oxygen consumptio n, one measure of BAT thermogenesis, Both CGP 12177 and RA treatment d ecreased levels of leptin mRNA to a similar extent. RA treatment had n o effect on mRNA levels of LPL in BAT or perirenal WAT. There were no changes in total DNA content, total protein content, or in the levels of beta-actin mRNA in either BAT or perirenal WAT upon administration oi RA or CGP 12177. Thus, the acute effects of RA paralleled the effec ts of the: beta(3)AR specific agonist, CGP 12177, on UCP1 and leptin g ene expression. This involvement of RA in positive regulation of UCP1 mRNA and negative regulation of leptin mRNA suggests a contrasting rol e for RA in energy homeostasis.