ABSTRACT β-Adrenergic receptor (βAR) agonists reduce body fat in mammals and birds. Synthetic lipid metabolism is decreased in βAR agonist-treated animals or in agonist-treated adipocytes in vitro. Degradative lipid metabolism is increased by βAR agonists in adipocytes in vitro and in vivo. The βAR agonist effects are blocked by βAR antagonists. In mammalian tissues, there are at least three distinct βAR subtypes; β-1 (β1AR), β-2 (β2AR), and β-3 (β3AR). Individual tissues have different proportions of subtypes. For example, greater than 85% of the βAR in rat heart is β1AR, in guinea pig lung is β2AR, and in rat adipose tissue is β3AR. Subtype distribution within a tissue varies with species (e.g., human heart has 65% β1AR and porcine adipocytes have less than 10% β3AR). There is species variation in the amino acid sequence of a βAR subtype. Thus, it is expected that some βAR agonists would have different effects in the same tissue in different species because of different βAR subtype distribution and(or) amino acid sequence. In support of these concepts, the pharmacology of βAR agonists and antagonists in adipocytes is in many cases species-specific. Cloning of individual βAR subtypes allows determination of the pharmacology of subtypes from that species. For example, the pharmacology of the cloned porcine β1AR, β2AR, and β3AR indicates selected agonists or antagonists can be used to assess the proportion of βAR subtypes. 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% β1AR. The effects produced by a βAR agonist (or antagonist) on adipose tissue in vivo depend not only on the species and the adipocyte βAR 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. In short, it is expected that individual βAR agonists would have somewhat different effects in different species.
Implications
The diversity of β-adrenergic receptors, the diversity of receptor subtype tissue distribution, and the pharmacology of receptor subtypes imply that individual β-adrenergic agonists would have somewhat different effects in adipocytes and adipose tissue of different species.
Key Words: Adipocytes, Beta-Adrenergic Receptors, Growth, Metabolism
© American Society of Animal Science. All rights reserved.
J. Anim. Sci. 80(E. Suppl. 1):E24-E29
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