Comparison of thermogenic activity induced by the new sympathomimetic Ro 16-8714 between normal and obese subjects

In a previous study, we demonstrated that the new beta-adrenoceptor agonist Ro 16-8714 possesses thermogenic property in normal male volunteers. The aim of the present study was to compare the metabolic response of lean vs obese individuals to a similar dose of this compound. Following an overnight fast, Ro 16-8714 (0.17 mg/kg fat free mass) or a placebo was given per os to six normal-weight subjects and to six moderately obese subjects. The rate of energy expenditure (EE) and the substrate utilization were determined by indirect calorimetry (hood system) before and for 6 h following the drug administration. Heart rate and blood pressure as well as plasma glucose, insulin and free fatty acid (FFA) concentrations were also measured at regular intervals throughout the study. The increment relative to base-line (mean +/- s.e.m.) in EE was similar in the two groups and averaged 4.0 +/- 1.4 per cent and 12.2 +/- 1.4 per cent with placebo and with Ro 16-8714 respectively in lean subjects, whereas the values reached 3.5 +/- 1.2 per cent and 14.4 +/- 2.0 per cent in obese subjects. Heart rate, systolic blood pressure, insulin and FFA were increased without any significant difference between the two groups. This study shows that Ro 16-8714 is a potent thermogenic agent both in normal and obese subjects.