Department of Neural and Behavioral Sciences, Penn State College of Medicine, Hershey, PA 17033, USA.
J Physiol. 2013 May 1;591(9):2357-72. doi: 10.1113/jphysiol.2012.249268. Epub 2013 Mar 4.
Diet-induced obesity (DIO) has been shown to alter the biophysical properties and pharmacological responsiveness of vagal afferent neurones and fibres, although the effects of DIO on central vagal neurones or vagal efferent functions have never been investigated. The aims of this study were to investigate whether high-fat diet-induced DIO also affects the properties of vagal efferent motoneurones, and to investigate whether these effects were reversed following weight loss induced by Roux-en-Y gastric bypass (RYGB) surgery. Whole-cell patch-clamp recordings were made from rat dorsal motor nucleus of the vagus (DMV) neurones in thin brainstem slices. The DMV neurones from rats exposed to high-fat diet for 12-14 weeks were less excitable, with a decreased membrane input resistance and decreased ability to fire action potentials in response to direct current pulse injection. The DMV neurones were also less responsive to superfusion with the satiety neuropeptides cholecystokinin and glucagon-like peptide 1. Roux-en-Y gastric bypass reversed all of these DIO-induced effects. Diet-induced obesity also affected the morphological properties of DMV neurones, increasing their size and dendritic arborization; RYGB did not reverse these morphological alterations. Remarkably, independent of diet, RYGB also reversed age-related changes of membrane properties and occurrence of charybdotoxin-sensitive (BK) calcium-dependent potassium current. These results demonstrate that DIO also affects the properties of central autonomic neurones by decreasing the membrane excitability and pharmacological responsiveness of central vagal motoneurones and that these changes were reversed following RYGB. In contrast, DIO-induced changes in morphological properties of DMV neurones were not reversed following gastric bypass surgery, suggesting that they may be due to diet, rather than obesity. These findings represent the first direct evidence for the plausible effect of RYGB to improve vagal neuronal health in the brain by reversing some effects of chronic high-fat diet as well as ageing. Vagovagal neurocircuits appear to remain open to modulation and adaptation throughout life, and understanding of these mechanisms may help in development of novel interventions to alleviate environmental (e.g. dietary) ailments and also alter neuronal ageing.
饮食诱导肥胖（DIO）已被证明会改变迷走传入神经元和纤维的生物物理特性和药理学反应性，尽管 DIO 对中枢迷走神经元或迷走传出功能的影响从未被研究过。本研究的目的是研究高脂肪饮食诱导的 DIO 是否也会影响迷走传出运动神经元的特性，并研究这些影响是否在 Roux-en-Y 胃旁路（RYGB）手术后减轻体重时得到逆转。在薄脑切片中从大鼠背侧迷走神经运动核（DMV）神经元进行全细胞膜片钳记录。暴露于高脂肪饮食 12-14 周的大鼠的 DMV 神经元兴奋性降低，膜输入电阻降低，对直流电脉冲注射产生动作电位的能力降低。DMV 神经元对饱食神经肽胆囊收缩素和胰高血糖素样肽 1 的灌流反应也降低。RYGB 逆转了所有这些 DIO 诱导的影响。饮食诱导的肥胖也影响 DMV 神经元的形态特性，增加其大小和树突分支；RYGB 没有逆转这些形态改变。值得注意的是，无论饮食如何，RYGB 还逆转了与年龄相关的膜特性变化和沙氏毒素敏感（BK）钙依赖性钾电流的发生。这些结果表明，DIO 还通过降低中枢迷走运动神经元的膜兴奋性和药理学反应性来影响中枢自主神经元的特性，并且这些变化在 RYGB 后得到逆转。相比之下，RYGB 手术后 DMV 神经元的形态改变没有得到逆转，这表明这些改变可能是由于饮食而不是肥胖引起的。这些发现代表了第一个直接证据，表明 RYGB 通过逆转慢性高脂肪饮食和衰老的一些影响来改善大脑中迷走神经元健康是合理的。迷走神经回路似乎在整个生命周期中仍然可以进行调节和适应，对这些机制的理解可能有助于开发新的干预措施来缓解环境（例如饮食）疾病，并改变神经元衰老。
