Russell S H, Small C J, Sunter D, Morgan I, Dakin C L, Cohen M A, Bloom S R
ICSM Endocrine Unit, Hammersmith Hospital, Du Cane Road, W12 ONN, London, UK.
Regul Pept. 2002 Mar 15;104(1-3):61-8. doi: 10.1016/s0167-0115(01)00349-4.
Orexin A, synthesised in the posterolateral hypothalamus, has widespread distribution including the paraventricular nucleus (PVN), which is rich in thyrotropin-releasing hormone (TRH) neurones. Nerve fibres in the PVN synapse on neurones that send polysynaptic projections to brown adipose tissue (BAT), which is important in thermogenesis. A number of observations suggests orexin A may be involved in regulation of metabolism and thermogenesis. We investigated the effect of orexin A injected intracerebroventricularly (ICV) on thyroid-stimulating hormone (TSH) and thyroid hormones in male rats. We then examined the effect of chronic iPVN injections of orexin A on plasma TSH and uncoupling protein-1 (UCP-1) protein in BAT. Orexin A (3 nmol) administered ICV significantly suppressed plasma TSH at 10 and 90 min. Orexin A (0.3 nmol) administered into the PVN twice daily for 3 days significantly increased day-time 2-h food intake, but did not significantly alter nocturnal food intake. Though chronic iPVN orexin A altered diurnal food intake, there was no effect on 24-h food intake or body weight. Furthermore, orexin A administered chronically into the PVN did not alter UCP-1 level in BAT, or plasma hormones relative to saline injected animals. Chronic iPVN orexin A does not appear to influence thermogenesis through activation of UCP-1 or the thyroid axis.
食欲素A在下丘脑后外侧合成,分布广泛,包括室旁核(PVN),该核富含促甲状腺激素释放激素(TRH)神经元。PVN中的神经纤维与向棕色脂肪组织(BAT)发出多突触投射的神经元形成突触,棕色脂肪组织在产热中起重要作用。多项观察结果表明食欲素A可能参与代谢和产热的调节。我们研究了脑室内注射(ICV)食欲素A对雄性大鼠促甲状腺激素(TSH)和甲状腺激素的影响。然后我们检查了慢性脑室内旁核注射食欲素A对血浆TSH和BAT中解偶联蛋白-1(UCP-1)蛋白的影响。脑室内注射3 nmol食欲素A在10分钟和90分钟时显著抑制血浆TSH。每天两次向室旁核注射0.3 nmol食欲素A,持续3天,显著增加白天2小时的食物摄入量,但对夜间食物摄入量没有显著影响。虽然慢性脑室内旁核注射食欲素A改变了昼夜食物摄入量,但对24小时食物摄入量或体重没有影响。此外,与注射生理盐水的动物相比,长期向室旁核注射食欲素A不会改变BAT中的UCP-1水平或血浆激素水平。慢性脑室内旁核注射食欲素A似乎不会通过激活UCP-1或甲状腺轴来影响产热。