C. Tonello et al., SR59230A BLOCKS BETA(3)-ADRENOCEPTOR-LINKED MODULATION OF UNCOUPLING PROTEIN-1 AND LEPTIN IN RAT BROWN ADIPOCYTES, European journal of pharmacology, 352(1), 1998, pp. 125-129
Experimental evidence suggests that, by stimulating energy expenditure
in brown fat, selective beta(3)-adrenoceptor agonists can reduce body
weight in obese rodents. In order to investigate further the physiolo
gical role of beta(3)-adrenoceptors in brown adipocytes, we analysed t
he effects of selective beta(3)-adrenoceptor agonists and antagonists
on uncoupling protein-1 and leptin gene expression in culture-differen
tiated brown fat cells. Our main findings were that: (i) the leptin ge
ne is expressed in brown adipocytes; (ii) the selective beta(3)-adreno
ceptor agonist, -2-yl]-(2R)-2-hydroxy-2-(3-chlorophenil)ethanamine hyd
rochloride (SR58611A), inhibits leptin gene while inducing uncoupling
protein-1 gene expression; (iii) these opposite effects of SR58611A ar
e antagonized by the selective beta(3)-adrenoceptor antagonist, SS-ena
ntiomer 2,3,4-tetrahydronaphth-1-ylaminol]-(2S)-2-propanol oxalate (SR
59230A), but not by the selective beta(1)-adrenoceptor antagonist -met
hyl-4-trifluoromethyl-2-imidazolyl)-phenoxy]-2 propanol (CGP20712A); a
nd (iv) these effects are due to increased cyclic AMP levels. These re
sults confirm by means of a different experimental approach that beta(
3)-adrenoceptors play a central role in controlling the expression of
genes that are important for brown fat function. (C) 1998 Elsevier Sci
ence B.V. All rights reserved.