Beta(1)/beta(2)/beta(3)-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.
Jimenez
Maria
M
Département de Biochimie Médicale, Centre Médical Universitaire, 1, rue Michel-Servet, 1211 Genève 4, Switzerland. maria.jimenez@medecine.unige.ch
Léger
Bertrand
B
Canola
Kriss
K
Lehr
Lorenz
L
Arboit
Patrizia
P
Seydoux
Josiane
J
Russell
Aaron P
AP
Giacobino
Jean Paul
JP
Muzzin
Patrick
P
Preitner
Frédéric
F
D002001:Adipose Tissue, Brown / Q000503:physiopathology; D000818:Animals; D015153:Blotting, Western; D003080:Cold Temperature; D008066:Lipolysis; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000235:genetics / Q000503:physiopathology*; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics / Q000502:physiology*; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000502:physiology*; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics / Q000502:physiology*; D012684:Sensory Thresholds; D013217:Starvation
D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D022702:Receptors, Adrenergic, beta-3