No effect of the Trp64Arg beta 3-adrenoceptor variant on in vivo lipolysis in subcutaneous adipose tissue.

A Trp64Arg variant in the human beta 3-adrenoceptor is associated with earlier onset of non-insulin-dependent diabetes mellitus and obesity in several populations. The present study investigated in vivo lipolysis in individuals homozygous for the 'variant' allele coding for arginine (Arg) in position 64 of the beta 3-adrenoceptor or homozygous for the 'wild type' tryptophan (Trp) allele. Subjects were 25 healthy, non-diabetic Pima Indians, 8 Arg (2 males, 6 females; aged 34 +/- 9 years, BMI 36.2 +/- 7.7 kg/m2, 43 +/- 11% body fat [mean +/- SD]), and 17 Trp (9 males, 8 females; aged 30 +/- 5 years, BMI 30.4 +/- 6.1 kg/m2, 39 +/- 9% body fat). After an overnight fast, a microdialysis probe was inserted in the subcutaneous adipose tissue and perfused with Ringer's solution. Dialysate was collected in 10-min fractions during a 30-min baseline and during 40 min with isoproterenol, a non-selective beta-adrenergic agonist, added to the perfusate (1 mumol/l). Changes in rate of lipolysis were assessed as changes in dialysate glycerol concentration. The relative changes in dialysate glycerol concentrations in response to isoproterenol, expressed as percent over baseline, were similar in the two groups (i.e. 63 +/- 30 and 74 +/- 28% in the Arg and Trp subjects, respectively). The results were also similar in the two groups after adjustment for sex and percentage of body fat. No differential effect of isoproterenol on blood flow was demonstrated between the two groups (assessed by the ethanol dilution technique). These results are consistent with in vitro studies showing no functional effect of the beta 3-adrenoceptor variant, and/or indicate that the beta 3-adrenoceptor is not very important for subcutaneous adipose tissue lipolysis.