β1/β2/β3-adrenoceptor knockout mice are obese and cold-sensitive but have normal lipolytic responses to fasting

Catecholamines are viewed as major stimulants of diet- and cold-induced thermogenesis and of fasting-induced lipolysis, through the beta-adrenoceptors (beta(1)/beta(2)/beta(3)). To test this hypothesis, we generated beta(1)/beta(2)/beta(3)-adrenoceptor triple knockout (TKO) mice and compared them to wild type animals. TKO mice exhibited normophagic obesity and cold-intolerance. Their brown fat had impaired morphology and lacked responses to cold of uncoupling protein-1 expression. In contrast, TKO mice had higher circulating levels of free fatty acids and glycerol at basal and fasted states, suggesting enhanced lipolysis. Hence, beta-adrenergic signalling is essential for the resistance to obesity and cold, but not for the lipolytic response to fasting. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.