The Arg 389 Gly beta1-adrenergic receptor gene polymorphism and human fat cell lipolysis.

Background: The beta1-adrenoceptor is a candidate gene for obesity because of its role in catecholamine-induced energy homeostasis. A common Arg 389 Gly variant polymorphism has been shown in recombinant cells to influence its-coupling properties.

Objective: To investigate the effect of the Arg 389 Gly beta1-adrenoceptor polymorphism on catecholamine-induced lipolysis in native human fat cells obtained by subcutaneous biopsy.

Subjects: Two-hundred and ninety-eight apparently healthy male and female subjects with a wide variation in body mass index (BMI, 18-60 kg/m2).

Measures: The lipolytic sensitivities and maximum lipolytic action of noradrenaline and the selective adrenoceptor agonists dobutamine (beta1), terbutaline (beta2) and CGP 12177 (beta3) were determined in isolated subcutaneous adipocytes and related to beta-adrenoceptor radioligand binding parameters.

Results: No differences in the sensitivity or maximum lipolytic capacity of the agonists were found between the genotypes. This was true both when all subjects were analyzed together and when subgroups (lean, obese, men, women) were analyzed separately. Radioligand binding to beta1- or beta2-adrenoceptors was also similar between genotypes. The polymorphism had no important influence on either BMI or the distribution of obese and non-obese subjects between the genotypes.

Conclusion: The distribution of the Arg 389 Gly polymorphism is similar in lean and obese subjects and has no apparent effect on the lipolytic response to beta-adrenergic stimulation in native human adipocytes. This suggests, despite the altered coupling properties reported in recombinant cells, that the Arg 386 Gly polymorphism has no important influence on human obesity.