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Journal of Lipid Research, Vol. 46, 2278-2281, October 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

Polymorphism of the AHSG gene is associated with increased adipocyte ß2-adrenoceptor function

Catharina Lavebratt^*, Elisabeth Dungner and Johan Hoffstedt^1,

^* Departments of Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden

Published, JLR Papers in Press, July 16, 2005. DOI 10.1194/jlr.M500201-JLR200

¹ To whom correspondence should be addressed. e-mail: johan.hoffstedt{at}medhs.ki.se

The alpha₂ Heremans-Schmid glycoprotein (AHSG) gene is implicated in the regulation of body fat and insulin sensitivity. The Met/Met genotype of the common single-nucleotide polymorphism (SNP), rs4917, in the AHSG gene has been shown to be associated with reduced plasma levels as well as lower body fat. Here, we studied the association of this variation with subcutaneous adipocyte lipolysis. Ninety-three obese and nonobese healthy men were genotyped for Thr230Met, and subcutaneous adipose tissue biopsies were analyzed for lipolysis characteristics. The Met/Met genotype was associated with a marked increase of 1.5 log units in the lipolytic sensitivity to the ß2-adrenoceptor agonist terbutaline (P = 0.0008) as compared with the Thr/Thr and Thr/Met genotypes. This corresponds to an approximately 35-fold increase in ß2-adrenoceptor function. The genotype effect was independent of body mass index and waist circumference. In contrast, lipolytic sensitivity to both the ß1-adrenoceptor agonist dobutamine (P = 0.25) and the 2A-adrenoceptor agonist clonidine (P = 0.54) was unaffected by the Thr230Met variation. Moreover, no difference in either maximal stimulation or inhibition of lipolysis was found between genotypes.

We conclude that a common variation (Thr230Met) in the AHSG gene is associated with a marked increase in ß2-adrenoceptor sensitivity in subcutaneous fat cells, which may be of importance in body weight regulation.

Supplementary key words alpha₂ Heremans-Schmid glycoprotein • adipose • alpha-adrenoceptor • beta-adrenoceptor • fat cell

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