Trp64Arg mutation of beta(3)-adrenoceptor gene deteriorates lipolysis induced by beta(3)-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 ons et of NIDDM, abdominal obesity, insulin resistance, and an increased capaci ty: to gain weight, We investigated whether lipolysis in human omental adip ocytes induced by a potent and selective human beta(3)-AR agonist (L-755,50 7) was affected by the Trp64Arg mutation of the beta(3)-adrenoceptor, using 18 omental fat samples obtained during total hysterectomy, The Trp64Arg mu tation was determined by polymerase chain reaction-restriction fragment len gth polymorphism analysis. analysis. ARG64 homozygous (n = 4) had a lower m edian 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 differenc e 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) cel ls(-1) . 90 min(-1)). We concluded that the Trp64Arg mutation of the beta(3 )-AR gene is associated with lower lipolytic activities.