Submitted to: American Society of Animal Science
Publication Type: Proceedings
Publication Acceptance Date: 10/17/2001
Publication Date: 1/1/2002
Citation: MERSMANN, H.J. BETA-ADRENERGIC RECEPTOR MODULATION OF ADIPOCYTE METABOLISM AND GROWTH. AMERICAN SOCIETY OF ANIMAL SCIENCE. v. 80. p. E24-E29.
Interpretive Summary: An interpretive summary is not required.
Technical Abstract: Beta-adrenergic receptor (betaAR) agonists reduce body fat in mammals and birds. Synthetic lipid metabolim is decreased in betaAR agonist-treated animals or in agonist-treated adipocytes in vitro. Degradative lipid metabolism is increased by betaAR agonists in adipocytes in vitro and in vivo. In mammalian tissues, there are at least three distinct betaAR subtypes; beta-1 (beta1AR), beta-2 (beta2AR), and beta-3 (beta3AR). Individual tissues have different proportions of subtypes. There is species variation in the amino acid sequence of a betaAR subtype. Thus, it is expected that some betaAR agonists would have different effects in the same tissue in different species because of different betaAR subtype distribution and(or) amino acid sequence. In support of these concepts, the pharmacology of betaAR agonists and antagonists in adipocytes is in many cases species-specific. Cloning of individual betaAR subtypes allows determination of the pharmacology of subtypes from that species. Nucleic acid sequences of the subtypes were used to prepare probes to quantify the subtype mRNA. The pharmacological and mRNA data agree rather closely and indicate porcine adipocytes contain over 70% beta1AR. Compared to the rat with 90% beta3AR, the effects produced by a betaAR agonist in vivo depend not only on the species and adipocyte betaAR subtype distribution, but also on the pharmacokinetics and pharmacodynamics of the compound in that species, including blood flow to the tissue, and the multiple metabolic and endocrine effects of the compound in other tissues of the body. It is expected that individual betaAR agonists would have somewhat different effects in different species.