Gastric vagal afferent modulation by leptin is influenced by food intake status
Gastric vagal afferent modulation by leptin is influenced by food intake status
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DOI：
10.1113/jphysiol.2012.247577
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发表时间：
2013-04-01
影响因子：
5.5
通讯作者：
Page, Amanda J.
中科院分区：
文献类型：
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作者：
Kentish, Stephen J.;O'Donnell, Tracey A.;Page, Amanda J.
能量摄入受到来自胃的迷走神经传入信号的强烈影响，并且还受到瘦素的调节。胃上皮细胞可能分泌瘦素，因此我们的目的是确定在不同的喂养条件下瘦素对胃迷走神经传入的直接影响。雌性C57 BL/6小鼠喂食标准实验室饮食、高脂肪饮食或限制食物。采用逆行追踪和逆转录聚合酶链反应（RT-PCR）技术检测胃迷走神经传入纤维中瘦素受体（Lep-R）及其信号转导分子的表达，采用顺行追踪和瘦素免疫组化技术检测胃迷走神经传入纤维终末与瘦素免疫阳性细胞的关系。在体外制备，以确定瘦素对胃迷走神经传入和第二信使通路的功能影响。瘦素增强迷走神经粘膜传入反应的触觉刺激，上皮细胞表达瘦素被发现接近迷走神经粘膜末梢。在禁食或饮食诱导的肥胖后，由瘦素引起的粘膜传入的增强作用丧失，胃粘膜传入的细胞体中的Lep-R表达减少。饮食诱导的肥胖小鼠的这些作用伴随着胃粘膜解剖迷走神经支配的减少。与此形成鲜明对比的是，在禁食或饮食诱导的肥胖后，瘦素实际上抑制了张力受体对扩张的反应。对胃张力受体的抑制作用是通过磷脂酰肌醇3-激酶依赖性激活大电导钙激活钾通道介导的。瘦素对胃粘膜迷走神经传入的兴奋作用是通过磷脂酶C依赖性激活经典瞬时受体电位通道介导的。提示瘦素对胃迷走神经传入兴奋性的影响是动态的，并与进食状态有关。奇怪的是，在肥胖症中，瘦素可能会减少食物摄入后胃扩张的反应。
Energy intake is strongly influenced by vagal afferent signals from the stomach, and is also modulated by leptin. Leptin may be secreted from gastric epithelial cells, so we aimed to determine the direct effect of leptin on gastric vagal afferents under different feeding conditions. Female C57BL/6 mice were fed standard laboratory diet, high-fat diet or were food restricted. The expression of leptin receptor (Lep-R) and its signal transduction molecules in vagal afferents was determined by retrograde tracing and reverse-transcription polymerase chain reaction, and the relationship between leptin-immunopositive cells and gastric vagal afferent endings determined by anterograde tracing and leptin immunohistochemistry. An in vitro preparation was used to determine the functional effects of leptin on gastric vagal afferents and the second messenger pathways involved. Leptin potentiated vagal mucosal afferent responses to tactile stimuli, and epithelial cells expressing leptin were found close to vagal mucosal endings. After fasting or diet-induced obesity, potentiation of mucosal afferents by leptin was lost and Lep-R expression reduced in the cell bodies of gastric mucosal afferents. These effects in diet-induced obese mice were accompanied by a reduction in anatomical vagal innervation of the gastric mucosa. In striking contrast, after fasting or diet-induced obesity, leptin actually inhibited responses to distension in tension receptors. The inhibitory effect on gastric tension receptors was mediated through phosphatidylinositol 3-kinase-dependent activation of large-conductance calcium-activated potassium channels. The excitatory effect of leptin on gastric mucosal vagal afferents was mediated by phospholipase C-dependent activation of canonical transient receptor potential channels. These data suggest the effect of leptin on gastric vagal afferent excitability is dynamic and related to the feeding state. Paradoxically, in obesity, leptin may reduce responses to gastric distension following food intake.