Effects of chronic treatment with noradrenaline or a specific beta3-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 beta3-adrenergic agonist, CL 316 243 (1 mg/kg x 24 hr), or to the physiological hormone, noradrenaline (5 mg/kg x 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 five times higher of NA increased the 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 retroperitoneal adipose tissue weight. Both treatments resulted in a marked desensitization (increased EC50 values) of the NA stimulated lipolysis of epididymal adipocytes. The effects of both treatments on maximal lipolysis were opposite. Indeed, chronic NA-treatment decreased the responsiveness of lipolysis while chronic treatment with CL increased the maximal stimulation of lipolysis to NA. Furthermore, dose-response curve for CL on lipolysis showed a marked functional desensitization of beta3-adrenergic response. 4. Our results demonstrate the high selectivity of beta3-adrenergic agonists to stimulate whole body energy expenditure and lipid mobilization in rodents. The present results point out for the first time an adrenergic desensitization of the lipolytic response after chronic administration of a beta3-agonist.
UMR 5578-CNRS, Laboratoire de Physiologie des Régulations Energétiques, Cellulaires et Moléculaires, Faculté de Médecine, Lyon, France.
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Atgié
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Faintrenie
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Carpéne
L J
LJ
Bukowiecki
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Géloën
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D004149:Dioxoles / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects*; D004822:Epididymis / Q000166:cytology / Q000378:metabolism; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D009929:Organ Size; D010101:Oxygen Consumption / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D004149:Dioxoles; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate; D009638:Norepinephrine