Rapid inhibition of ob gene expression and circulating leptin levels in lean mice by the beta 3-adrenoceptor agonists BRL 35135A and ZD2079

The acute effect of two selective beta 3-adrenoceptor agonists, BRL, 35135A and ZD2079, on the expression of the ob gene and plasma leptin levels has been examined in mice. By 4-5 h after the administration of either beta 3-agonist to lean animals there was a major loss of ob mRNA from epididymal white adipose tissue. This was accompanied by a substantial fall in circulating leptin levels, as measured by an ELISA. Even 24 h after the first administration of beta 3-agonists, ob mRNA levels and circulating leptin levels remained low. In contrast to lean animals, treatment with BRL 35135A had only a minor effect on ob mRNA levels in obese (ob/ob) mice. Regulation of leptin production appears to involve a negative feedback loop to white adipose tissue through the sympathetic nervous system suppressing ob gene transcription via beta 3-adrenoceptors; an impairment in this loop is evident in the ob/ob mutant. (C) 1996 Academic Press, Inc.