Trp64Arg mutation of β3-adrenoceptor gene deteriorates lipolysis induced by β3-adrenoceptor agonist in human omental adipocytes

The recently described variant of the human beta(3)-adrenergic receptor (AR) gene located mainly in visceral adipocytes is associated with earlier onset of NIDDM, abdominal obesity, insulin resistance, and an increased capacity: to gain weight, We investigated whether lipolysis in human omental adipocytes induced by a potent and selective human beta(3)-AR agonist (L-755,507) was affected by the Trp64Arg mutation of the beta(3)-adrenoceptor, using 18 omental fat samples obtained during total hysterectomy, The Trp64Arg mutation was determined by polymerase chain reaction-restriction fragment length polymorphism analysis. analysis. ARG64 homozygous (n = 4) had a lower median effective concentration (EC50) and lower responsiveness compared with wild-type (n = 8) (EC50: -6.55 +/- 0.21 vs. -7.53 +/- 0.35 log mol/l, P = 0.007; responsiveness 3.48 +/- 0.32 vs. 5.76 +/- 0.36 mu mol . 10(5) cells(-1) . 90 min(-1), P = 0.014, respectively), although there was no difference in lipolysis induced by isoproterenol or CGP12177. Trp64Arg heterozygous (n = 6) also had a significantly lower EC50 and lower responsiveness (EC50: -6.18 +/- 0.09 log mol/l; responsiveness: 4.17 +/- 0.33 mu mol . 10(5) cells(-1) . 90 min(-1)). We concluded that the Trp64Arg mutation of the beta(3)-AR gene is associated with lower lipolytic activities.