leptin and talibegron-hydrochloride

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.

Topics: Adipose Tissue; Adrenergic beta-Agonists; Animals; Base Sequence; Blotting, Northern; Epididymis; Leptin; Male; Mice; Mice, Obese; Obesity; Oligonucleotides, Antisense; Phenethylamines; Phenylacetates; Protein Biosynthesis; Proteins; Receptors, Adrenergic, beta; Receptors, Adrenergic, beta-3; Receptors, Leptin; Reference Values; RNA, Messenger; Thinness; Transcription, Genetic