Hindbrain Administration of Oxytocin Reduces Food Intake, Weight Gain and Activates Catecholamine Neurons in the Hindbrain Nucleus of the Solitary Tract in Rats.

Hindbrain Administration of Oxytocin Reduces Food Intake, Weight Gain and Activates Catecholamine Neurons in the Hindbrain Nucleus of the Solitary Tract in Rats.
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DOI:
10.3390/jcm10215078
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发表时间:
2021-10-29
影响因子:
3.9
通讯作者:
Blevins JE
Blevins JE
中科院分区:
医学2区
文献类型:
--
作者:
Anekonda VT;Thompson BW;Ho JM;Roberts ZS;Edwards MM;Nguyen HK;Dodson AD;Wolden-Hanson T;Chukri DW;Herbertson AJ;Graham JL;Havel PJ;Wietecha TA;O'Brien KD;Blevins JE

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现有研究表明,中枢神经系统催产素 (OT) 信号传导对于能量平衡的控制很重要,但尚不清楚哪些神经元可能有助于这些作用。我们的目标是检查 (1) 对第三脑室(3V;前脑)和第四脑室(4V;后脑)进行急性 OT 给药的剂量反应效应,以评估前脑和后脑部位对 OT 的敏感性;(2) 长期 4V 给药 OT 在多大程度上减少与饮食引起的肥胖进展相关的体重增加;(3) 孤束核 (NTS) 儿茶酚胺神经元是否是 4V 的下游靶点加时。最初,我们检查了 3V 和 4V OT(0.04、0.2、1 或 5 μg)的剂量反应效应。 3V 和 4V OT (5 μg) 分别抑制 0.5 小时食物摄入量 71.7 ± 6.0% 和 60 ± 12.9%。 4V OT(0.04、0.2、1 μg)分别使食物摄入量减少了 30.9 ± 12.9、42.1 ± 9.4 和 56.4 ± 9.0%,而 3V OT(1 μg)给药仅有效减少 0.5 小时食物摄入量 38.3 ± 10.9%。我们随后发现,与慢性 3V 输注一样,长期 4V OT 输注可减少体重增加(特定于脂肪量),并倾向于降低高脂饮食 (HFD) 喂养大鼠的血浆瘦素,部分原因是通过减少能量摄入。最后,我们确定 4V OT 相对于载体 (12 ± 3) 增加了后脑尾部 NTS Fos (+) 神经元 (156 ± 25) 的数量。相对于载体 (0.8 ± 0.3%),4V OT 还诱导酪氨酸羟化酶 (TH;儿茶酚胺神经元标记) (+) 神经元 (25 ± 7%) 中的 Fos。总的来说,这些发现支持这样的假设:后脑内的 OT 可有效减少食物摄入、体重增加和肥胖,并且除了非儿茶酚胺能神经元之外,NTS 儿茶酚胺神经元也是 CNS OT 的下游目标。
Existing studies show that CNS oxytocin (OT) signaling is important in the control of energy balance, but it is unclear which neurons may contribute to these effects. Our goals were to examine (1) the dose-response effects of acute OT administration into the third (3V; forebrain) and fourth (4V; hindbrain) ventricles to assess sensitivity to OT in forebrain and hindbrain sites, (2) the extent to which chronic 4V administration of OT reduces weight gain associated with the progression of diet-induced obesity, and (3) whether nucleus tractus solitarius (NTS) catecholamine neurons are downstream targets of 4V OT. Initially, we examined the dose-response effects of 3V and 4V OT (0.04, 0.2, 1, or 5 μg). 3V and 4V OT (5 μg) suppressed 0.5-h food intake by 71.7 ± 6.0% and 60 ± 12.9%, respectively. 4V OT (0.04, 0.2, 1 μg) reduced food intake by 30.9 ± 12.9, 42.1 ± 9.4, and 56.4 ± 9.0%, respectively, whereas 3V administration of OT (1 μg) was only effective at reducing 0.5-h food intake by 38.3 ± 10.9%. We subsequently found that chronic 4V OT infusion, as with chronic 3V infusion, reduced body weight gain (specific to fat mass) and tended to reduce plasma leptin in high-fat diet (HFD)-fed rats, in part, through a reduction in energy intake. Lastly, we determined that 4V OT increased the number of hindbrain caudal NTS Fos (+) neurons (156 ± 25) relative to vehicle (12 ± 3). The 4V OT also induced Fos in tyrosine hydroxylase (TH; marker of catecholamine neurons) (+) neurons (25 ± 7%) relative to vehicle (0.8 ± 0.3%). Collectively, these findings support the hypothesis that OT within the hindbrain is effective at reducing food intake, weight gain, and adiposity and that NTS catecholamine neurons in addition to non-catecholaminergic neurons are downstream targets of CNS OT.
DOI: 10.1371/journal.pone.0005370
发表时间: 2009
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