Abstract
The alpha(2) 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 beta2-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 beta2-adrenoceptor function. The genotype effect was independent of body mass index and waist circumference. In contrast, lipolytic sensitivity to both the beta1-adrenoceptor agonist dobutamine (P=0.25) and the alpha2A-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 beta2-adrenoceptor sensitivity in subcutaneous fat cells, which may be of importance in body weight regulation.
Highlights
The alpha2 Heremans-Schmid glycoprotein (AHSG) gene is implicated in the regulation of body fat and insulin sensitivity
A double-single nonsynonymous nucleotide substitution [single-nucleotide polymorphism (SNP)] at amino acid positions 230 and 238 has been described [3] and was recently found to be associated with decreased plasma concentrations of AHSG [4]. In agreement with these findings, we have shown that homozygosity for the rs2593813:G–rs4917:minor allele T (Met)–rs4918: Ser haplotype of the AHSG gene conferred an increased risk for leanness in men [5], which in turn suggests a protective role of AHSG gene variation in body fat accumulation in man
The present study was designed to evaluate whether the rs4917 (Thr230Met) variation in the AHSG gene is associated with fat cell function by investigating subcutaneous fat cell lipolysis in 93 healthy obese and nonobese male subjects
Summary
The alpha Heremans-Schmid glycoprotein (AHSG) gene is implicated in the regulation of body fat and insulin sensitivity. We conclude that a common variation (Thr230Met) in the AHSG gene is associated with a marked increase in 2-adrenoceptor sensitivity in subcutaneous fat cells, which may be of importance in body weight regulation.—Lavebratt, C., E. A double-single nonsynonymous nucleotide substitution [single-nucleotide polymorphism (SNP)] at amino acid positions 230 (rs4917, Thr230Met) and 238 (rs4918, Thr238Ser) has been described [3] and was recently found to be associated with decreased plasma concentrations of AHSG [4] In agreement with these findings, we have shown that homozygosity for the rs2593813:G–rs4917:Met–rs4918: Ser haplotype of the AHSG gene conferred an increased risk for leanness in men [5], which in turn suggests a protective role of AHSG gene variation in body fat accumulation in man. The present study was designed to evaluate whether the rs4917 (Thr230Met) variation in the AHSG gene is associated with fat cell function by investigating subcutaneous fat cell lipolysis in 93 healthy obese and nonobese male subjects
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