EFFECTS OF CHRONIC TREATMENT WITH NORADRENALINE OR A SPECIFIC BETA-3-ADRENERGIC AGONIST, CL-316,243, ON ENERGY-EXPENDITURE AND EPIDIDYMAL ADIPOCYTE LIPOLYTIC-ACTIVITY IN RAT

1. The effects of 7 days exposure to a specific beta 3-adrenergic agon ist, CL 316 243 (1 mg/kg.24 hr), or to the physiological hormone, nora drenaline (5 mg/kg.24 hr), were tested on energy expenditure and on in vitro lipolysis in male Sprague-Dawley rats. 2. At the second day of treatment, the total energy expenditure and the resting metabolic rate were increased by 20 and 30%, respectively, in the CL-treated group. Under the same conditions, a dose live times higher of NA increased th e resting metabolic rate by 11% without any significant change in the total daily energy expenditure. 3. The CL-treated group showed a lower weight gain, correlated with a significant reduction in retroperitone al adipose tissue weight. Both treatments resulted in a marked desensi tization (increased EC50 values) of the NA stimulated lipolysis of epi didymal adipocytes. The effects of both treatments on maximal lipolysi s were opposite. Indeed, chronic NA-treatment decreased the responsive ness of lipolysis while chronic treatment with CL increased the maxima l stimulation of lipolysis to NA. Furthermore, dose-response curve for CL on lipolysis showed a marked functional desensitization of beta 3- adrenergic response. 4. Our results demonstrate the high selectivity o f beta 3-adrenergic agonists to stimulate whole body energy expenditur e and lipid mobilization in rodents. The present results point out for the first time an adrenergic desensitization of the lipolytic respons e after chronic administration of a beta 3-agonist. (C) 1998 Elsevier Science Inc.