The full expression of fasting-induced torpor requires β3-adrenergic receptor signaling

被引:54
作者
Swoap, SJ [1 ]
Gutilla, MJ
Liles, LC
Smith, RO
Weinshenker, D
机构
[1] Williams Coll, Dept Biol, Williamstown, MA 01267 USA
[2] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA 30322 USA
关键词
adipose; beta-adrenergic receptor; norepinephrine; knock-out mice; leptin; sympathetic nervous system; fasting;
D O I
10.1523/JNEUROSCI.3721-05.2006
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Torpor, a controlled rapid drop in metabolic rate and body temperature (T-b), is a hypometabolic adaptation to stressful environmental conditions, which occurs in many small mammals, marsupials, and birds. To date, signaling pathways required for torpor have not been identified. We examined the role of the sympathetic nervous system (SNS) in mediating the torpor adaptation to fasting by telemetrically monitoring the T-b of dopamine beta-hydroxylase knock-out (Dbh -/-) mice, which lack the ability to produce the SNS transmitters, norepinephrine (NE), and epinephrine. Control (Dbh +/-) mice readily reduced serum leptin levels and entered torpor after a fast in a cool environment. In contrast, (Dbh -/-) mice failed to reduce serum leptin and enter torpor under fasting conditions, whereas restoration of peripheral but not central NE lowered serum leptin levels and rescued the torpor response. Torpor was expressed in fasted Dbh -/- mice immediately after administration of either the nonselective beta-adrenergic receptor agonist isoproterenol or the beta 3-adrenergic receptor (AR)-specific agonist CL 316243 [disodium (RR)-5-[2-[2-(3-chlorophenyl)-2-hydroxyethyl]-amino] propyl]-1,3-benzodioxazole- 2,2-dicarboxylate], but not after administration of beta 1, beta 2, or alpha 1 agonists. Importantly, the beta 3-specific antagonist SR 59230A [3-(2-ethylphenoxy)-1-[(1,S)-1,2,3,4-tetrahydronapth-1-ylamino]-2S-2-propanol oxalate] severely blunted fasting-induced torpor in control mice, whereas other AR antagonists were ineffective. These results define a critical role of peripheral SNS activity at beta 3-AR-containing tissues in the torpor adaptation to limited energy availability and cool ambient temperature.
引用
收藏
页码:241 / 245
页数:5
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