Brainstem thyrotropin-releasing hormone regulates food intake through vagal-dependent cholinergic stimulation of ghrelin secretion
Brainstem thyrotropin-releasing hormone regulates food intake through vagal-dependent cholinergic stimulation of ghrelin secretion
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DOI：
10.1210/en.2006-0820
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发表时间：
2006-12-01
期刊：
影响因子：
4.8
通讯作者：
Yang, Hong
中科院分区：
文献类型：
--
作者：
Ao, Yan;Go, Vay Liang W.;Yang, Hong
脑干对于调节对饥饿的能量反应是必不可少的。脑干TRH在支配脑干的中缝尾侧核以及脊髓迷走和交感运动神经元中合成。脑池内注射（ic）稳定的TRH类似物RX 77368（7.5-25 ng）剂量依赖性地刺激自由进食大鼠的固体食物摄入量增加2.4- 3倍，这种作用持续3 h。相比之下，25 ng RX 77368注射到侧脑室中仅在第一小时内诱导延迟且不显著的食欲促进作用。在戊巴比妥麻醉大鼠中，RX 77368（50 ng）ic诱导血清总生长素释放肽水平出现显著双峰增加，从基础水平8.7 +/- 1.7 ng/ml增加至30 min时的13.4 +/- 2.4 ng/ml和90 min时的14.5 +/- 2.0 ng/ml，双侧迷走神经切断术（~ 60分钟）或阿托品预处理（2 mg/kg，~ 30分钟）可防止这种情况，但双侧肾上腺切除术（~ 60分钟）可扩大这种情况。TRH类似物ic诱导的自由进食大鼠的摄食被外周阿托品或ghrelin受体拮抗剂（D-Lys-3）-GHRP-6（10 μ mol/kg）或ic Y1受体拮抗剂122 PU 91（10 nmol/5 μ l）消除。脑干TRH mRNA和TRH受体1 mRNA在禁食24和48 h大鼠中分别增加57-58和33-35%，并在3 h后恢复到进食水平。自然的食物摄入量过夜禁食大鼠显着减少IC TRH抗体，IC Y1拮抗剂，和外周阿托品。这些数据确立了脑干TRH在迷走神经生长激素释放肽介导的刺激食物摄入中的生理作用，其中涉及与脑干Y1受体的相互作用。
The brainstem is essential for mediating energetic response to starvation. Brain stem TRH is synthesized in caudal raphe nuclei innervating brainstem and spinal vagal and sympathetic motor neurons. Intracisternal injection (ic) of a stable TRH analog RX77368 (7.5-25 ng) dose-dependently stimulated solid food intake by 2.4- to 3-fold in freely fed rats, an effect that lasted for 3 h. By contrast, RX77368 at 25 ng injected into the lateral ventricle induced a delayed and insignificant orexigenic effect only in the first hour. In pentobarbital-anesthetized rats, RX77368 (50 ng) ic induced a significant bipeak increase in serum total ghrelin levels from the basal of 8.7 +/- 1.7 ng/ml to 13.4 +/- 2.4 ng/ml at 30 min and 14.5 +/- 2.0 ng/ml at 90 min, which was prevented by either bilateral vagotomy (-60 min) or atropine pretreatment (2 mg/kg, -30 min) but magnified by bilateral adrenalectomy (-60 min). TRH analog ic-induced food intake in freely fed rats was abolished by either peripheral atropine or ghrelin receptor antagonist (D-Lys-3)-GHRP-6 (10 mu mol/kg) or ic Y1 receptor antagonist 122PU91 (10 nmol/5 mu l). Brain stem TRH mRNA and TRH receptor 1 mRNA increased by 57-58 and 33-35% in 24- and 48-h fasted rats and returned to the fed levels after a 3-h refeeding. Natural food intake in overnight fasted rats was significantly reduced by ic TRH antibody, ic Y1 antagonist, and peripheral atropine. These data establish a physiological role of brainstem TRH in vagal-ghrelin-mediated stimulation of food intake, which involves interaction with brainstem Y1 receptors.