High fat diet attenuates glucose-dependent facilitation of 5-HT3 -mediated responses in rat gastric vagal afferents.
High fat diet attenuates glucose-dependent facilitation of 5-HT3 -mediated responses in rat gastric vagal afferents.
复制标题
高脂肪饮食减弱了大鼠胃迷走神经传入中葡萄糖依赖性 5-HT3 介导的反应。
DOI：
10.1113/jp271558
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发表时间：
2016
期刊：
影响因子：
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通讯作者：
Browning,KirsteenN
中科院分区：
文献类型：
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作者：
Troy,AmandaE;Simmonds,SarahS;Stocker,SeanD;Browning,KirsteenN
葡萄糖调节胃迷走神经传入神经元上5-HT 3受体的密度和功能。饮食诱导的肥胖损害迷走神经传入神经的兴奋性和反应性。在这项研究中，我们评估了高脂饮食（HFD）在肥胖发生之前，HFD损害了胃迷走神经传入的5-HT反应的葡萄糖依赖性调节。我们表明，HFD不会改变胃迷走神经传入的反应。这些结果表明，葡萄糖依赖性迷走神经传入信号受到损害的相对较短的时间暴露于HFD以及在肥胖症或糖尿病失调的发展之前。AbstractGlucose调节胃迷走神经传入神经元上的5-HT 3受体的密度和功能。由于饮食诱导的肥胖减弱了胃迷走神经传入对几种神经激素的反应性，本研究的目的是确定高脂饮食（HFD）是否会在肥胖发生前损害胃迷走神经传入中5-HT反应的葡萄糖依赖性调节。大鼠喂食对照或HFD（分别来自脂肪的14%或60%千卡）长达8周。神经生理学记录评估了5-HT在急性高血压前后增加胃前迷走传入神经（货车）活性的能力，而胃投射结状神经元的电生理学记录评估了葡萄糖在体外调节5-HT反应的能力。免疫细胞化学研究确定了5-HT 3受体神经元分布的改变。5-HT和胆囊收缩素（CCK）诱导所有大鼠货车活性的剂量依赖性增加; HFD减弱了对CCK的反应，但对5-HT无影响。在对照大鼠中，5-HT诱导的反应被急性高血压放大，但在HFD大鼠中没有。同样，尽管5-HT在体外的对照和HFD胃结状神经元中都诱导了内向电流，但仅在对照大鼠中，急性高血压放大了5-HT反应和受体分布。这些数据表明，虽然HFD不影响胃投射迷走神经传入对5-HT的反应，但它减弱了葡萄糖放大5-HT效应的能力。这表明葡萄糖依赖性迷走神经传入信号在肥胖或代谢紊乱之前很长时间暴露于HFD会受到损害。
Key pointsGlucose regulates the density and function of 5‐HT3receptors on gastric vagal afferent neurones.Diet‐induced obesity compromises the excitability and responsiveness of vagal afferents.In this study, we assessed whether exposure to a high fat diet (HFD) compromises the glucose‐dependent modulation of 5‐HT responses in gastric vagal afferents prior to the development of obesity.We show that HFD does not alter the response of gastric vagal afferent nerves and neurones to 5‐HT but attenuates the ability of glucose to amplify 5‐HT3‐induced responses.These results suggest that glucose‐dependent vagal afferent signalling is compromised by relatively short periods of exposure to HFD well in advance of the development of obesity or glycaemic dysregulation.AbstractGlucose regulates the density and function of 5‐HT3receptors on gastric vagal afferent neurones. Since diet‐induced obesity attenuates the responsiveness of gastric vagal afferents to several neurohormones, the aim of the present study was to determine whether high fat diet (HFD) compromises the glucose‐dependent modulation of 5‐HT responses in gastric vagal afferents prior to the development of obesity. Rats were fed control or HFD (14% or 60% kilocalories from fat, respectively) for up to 8 weeks. Neurophysiological recordings assessed the ability of 5‐HT to increase anterior gastric vagal afferent nerve (VAN) activityin vivobefore and after acute hyperglycaemia, while electrophysiological recordings from gastric‐projecting nodose neurones assessed the ability of glucose to modulate the 5‐HT responsein vitro. Immunocytochemical studies determined alterations in the neuronal distribution of 5‐HT3receptors. 5‐HT and cholecystokinin (CCK) induced dose‐dependent increases in VAN activity in all rats; HFD attenuated the response to CCK, but not 5‐HT. The 5‐HT‐induced response was amplified by acute hyperglycaemia in control, but not HFD, rats. Similarly, although 5‐HT induced an inward current in both control and HFD gastric nodose neuronesin vitro, the 5‐HT response and receptor distribution was amplified by acute hyperglycaemia only in control rats. These data suggest that, while HFD does not affect the response of gastric‐projecting vagal afferents to 5‐HT, it attenuates the ability of glucose to amplify 5‐HT effects. This suggests that glucose‐dependent vagal afferent signalling is compromised by short periods of exposure to HFD well in advance of obesity or glycaemic dysregulation.