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Beta-Adrenergic receptor modulation of adipocyte metabolism and growth

USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030-2600

¹ Correspondence: E-mail: mersmann{at}bcm.tmc.edu.

Abstract

ß-Adrenergic receptor (ßAR) agonists reduce body fat in mammals and birds. Synthetic lipid metabolism is decreased in ßAR agonist-treated animals or in agonist-treated adipocytes in vitro. Degradative lipid metabolism is increased by ßAR agonists in adipocytes in vitro and in vivo. The ßAR agonist effects are blocked by ßAR antagonists. In mammalian tissues, there are at least three distinct ßAR subtypes; ß-1 (ß1AR), ß-2 (ß2AR), and ß-3 (ß3AR). Individual tissues have different proportions of subtypes. For example, greater than 85% of the ßAR in rat heart is ß1AR, in guinea pig lung is ß2AR, and in rat adipose tissue is ß3AR. Subtype distribution within a tissue varies with species (e.g., human heart has 65% ß1AR and porcine adipocytes have less than 10% ß3AR). There is species variation in the amino acid sequence of a ßAR subtype. Thus, it is expected that some ßAR agonists would have different effects in the same tissue in different species because of different ßAR subtype distribution and(or) amino acid sequence. In support of these concepts, the pharmacology of ßAR agonists and antagonists in adipocytes is in many cases species-specific. Cloning of individual ßAR subtypes allows determination of the pharmacology of subtypes from that species. For example, the pharmacology of the cloned porcine ß1AR, ß2AR, and ß3AR indicates selected agonists or antagonists can be used to assess the proportion of ßAR 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% ß1AR. The effects produced by a ßAR agonist (or antagonist) on adipose tissue in vivo depend not only on the species and the adipocyte ßAR 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 ßAR agonists would have somewhat different effects in different species.

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