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

Biochem Biophys Res Commun. 1996 Nov 12;228(2):605-10. doi: 10.1006/bbrc.1996.1704.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism*
  • Adrenergic beta-Agonists / pharmacology*
  • Animals
  • Base Sequence
  • Blotting, Northern
  • Epididymis
  • Leptin
  • Male
  • Mice
  • Mice, Obese
  • Obesity / metabolism*
  • Oligonucleotides, Antisense
  • Phenethylamines / pharmacology*
  • Phenylacetates / pharmacology*
  • Protein Biosynthesis*
  • Proteins / metabolism
  • RNA, Messenger / biosynthesis
  • Receptors, Adrenergic, beta / drug effects
  • Receptors, Adrenergic, beta / physiology*
  • Receptors, Adrenergic, beta-3
  • Receptors, Leptin
  • Reference Values
  • Thinness
  • Transcription, Genetic* / drug effects


  • Adrenergic beta-Agonists
  • Leptin
  • Oligonucleotides, Antisense
  • Phenethylamines
  • Phenylacetates
  • Proteins
  • RNA, Messenger
  • Receptors, Adrenergic, beta
  • Receptors, Adrenergic, beta-3
  • Receptors, Leptin
  • leptin receptor, mouse
  • BRL 35135
  • talibegron hydrochloride