Leptin resistance in vagal afferent neurons inhibits cholecystokinin signaling and satiation in diet induced obese rats.
Leptin resistance in vagal afferent neurons inhibits cholecystokinin signaling and satiation in diet induced obese rats.
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DOI：
10.1371/journal.pone.0032967
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Raybould HE
中科院分区：
文献类型：
--
作者：
de Lartigue G;Barbier de la Serre C;Espero E;Lee J;Raybould HE
胃肠激素胆囊收缩素（CCK）通过激活迷走神经传入神经元（货车）上的CCK 1受体，在调节进餐量和进餐时间方面发挥重要作用。瘦素通过早期生长反应1（EGR 1）依赖性途径增强货车中的CCK信号传导，从而增加其对CCK的敏感性。作为对长期摄入高脂肪饮食的响应，货车发展出瘦素抵抗，并且CCK的饱腹作用降低。我们验证了货车中的瘦素抵抗负责减少CCK信号传导和饱食的假设。对瘦素信号传导敏感的瘦Zucker大鼠在施用CCK 8 S（0.22 nmol/kg，i. p.）后显著减少了它们的食物摄入，而对瘦素不敏感的肥胖Zucker大鼠则没有。肥胖Zucker大鼠货车中CCK信号传导减少，阻止CCK诱导的Y2受体上调和黑色素浓集激素1受体（MCH 1 R）和大麻素受体（CB 1）下调。在货车从饮食诱导肥胖（DIO）Sprague道利大鼠，以前被证明成为瘦素抵抗，我们证明，减少EGFR 1表达导致货车的敏感性降低CCK和减少CCK诱导的抑制食物摄入。DIO大鼠货车对CCK的敏感性降低，导致Y2表达减少，CB 1和MCH 1 R表达增加。这些影响与DIO大鼠的摄食过多发作一致。货车中的瘦素信号传导是适当的CCK信号传导和饱足所必需的。在高脂喂养的反应中，瘦素抵抗的发生降低了货车对CCK的敏感性，从而降低了CCK的饱腹效应。
The gastrointestinal hormone cholecystokinin (CCK) plays an important role in regulating meal size and duration by activating CCK1 receptors on vagal afferent neurons (VAN). Leptin enhances CCK signaling in VAN via an early growth response 1 (EGR1) dependent pathway thereby increasing their sensitivity to CCK. In response to a chronic ingestion of a high fat diet, VAN develop leptin resistance and the satiating effects of CCK are reduced. We tested the hypothesis that leptin resistance in VAN is responsible for reducing CCK signaling and satiation. Lean Zucker rats sensitive to leptin signaling, significantly reduced their food intake following administration of CCK8S (0.22 nmol/kg, i.p.), while obese Zucker rats, insensitive to leptin, did not. CCK signaling in VAN of obese Zucker rats was reduced, preventing CCK-induced up-regulation of Y2 receptor and down-regulation of melanin concentrating hormone 1 receptor (MCH1R) and cannabinoid receptor (CB1). In VAN from diet-induced obese (DIO) Sprague Dawley rats, previously shown to become leptin resistant, we demonstrated that the reduction in EGR1 expression resulted in decreased sensitivity of VAN to CCK and reduced CCK-induced inhibition of food intake. The lowered sensitivity of VAN to CCK in DIO rats resulted in a decrease in Y2 expression and increased CB1 and MCH1R expression. These effects coincided with the onset of hyperphagia in DIO rats. Leptin signaling in VAN is required for appropriate CCK signaling and satiation. In response to high fat feeding, the onset of leptin resistance reduces the sensitivity of VAN to CCK thus reducing the satiating effects of CCK.
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影响因子：
--
作者：
CLEARY, MP;VASSELLI, JR;GREENWOOD, MRC
通讯作者：
GREENWOOD, MRC
DOI：
10.1152/ajpgi.00098.2010
发表时间：
2010-08-01
影响因子：
4.5
作者：
de La Serre, Claire Barbier;Ellis, Collin L.;Raybould, Helen E.
通讯作者：
Raybould, Helen E.
DOI：
10.1111/j.1440-1746.1989.tb01741.x
发表时间：
1989-09-01
影响因子：
4.1
作者：
HEDDLE, R;COLLINS, PJ;HOUGHTON, LA
通讯作者：
HOUGHTON, LA
影响因子：
29.4
作者：
De Lartigue, Guillaume;Dimaline, Rod;Dockray, Graham J.
通讯作者：
Dockray, Graham J.
胆囊动蛋白调节在为胃提供的迷走神经元中Y2受体的表达。
DOI：
10.1523/jneurosci.2493-08.2008
发表时间：
2008-11-05
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Burdyga G;de Lartigue G;Raybould HE;Morris R;Dimaline R;Varro A;Thompson DG;Dockray GJ
通讯作者：
Dockray GJ