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.
Trayhurn
P
P
Division of Biochemical Sciences, Rowett Research Institute, Bucksburn, Aberdeen, Scotland, United Kingdom.
Duncan
J S
JS
Rayner
D V
DV
Hardie
L J
LJ
D000273:Adipose Tissue / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D004822:Epididymis; D020738:Leptin; D008297:Male; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000378:metabolism*; D016376:Oligonucleotides, Antisense; D010627:Phenethylamines / Q000494:pharmacology*; D010648:Phenylacetates / Q000494:pharmacology*; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D022702:Receptors, Adrenergic, beta-3; D054411:Receptors, Leptin; D012016:Reference Values; D013851:Thinness; D014158:Transcription, Genetic / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D020738:Leptin; D016376:Oligonucleotides, Antisense; D010627:Phenethylamines; D010648:Phenylacetates; D011506:Proteins; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D022702:Receptors, Adrenergic, beta-3; D054411:Receptors, Leptin; C515447:leptin receptor, mouse; C063157:BRL 35135; C102383:talibegron hydrochloride