Williams Diana L, Grill Harvey J, Cummings David E, Kaplan Joel M
Veterans Affairs Puget Sound Health Care System, 1660 South Columbian Way, Mail Stop 111-ENDO, Seattle, Washington 98108, USA.
Endocrinology. 2003 Dec;144(12):5184-7. doi: 10.1210/en.2003-1059. Epub 2003 Oct 2.
Plasma ghrelin levels are responsive to short- and long-term nutrient fluctuation, rapidly decreasing with food consumption and increasing with food deprivation or weight loss. We hypothesized a vagal contribution to both responses. Nutrient-related ghrelin suppression may be mediated by gastrointestinal load-related vagal afferent activity, or depend upon vagal efferent input to the foregut, where most ghrelin is produced. Similarly, the deprivation-induced ghrelin rise could require state-related vagal afferent or efferent activity. Here, we examined the role of the vagus nerve in the regulation of plasma ghrelin by sampling blood from rats with subdiaphragmatic vagotomy and from sham-operated controls over 48 h of food deprivation, and before and after gastric gavage of liquid diet. Vagotomy affected neither baseline ghrelin levels nor the suppression of ghrelin by a nutrient load. The food deprivation-induced elevation of plasma ghrelin levels ( approximately 160% of baseline), however, was completely prevented by subdiaphragmatic vagotomy. In a separate experiment, the deprivation-related rise in plasma ghrelin was substantially reduced by atropine methyl nitrate treatment, indicating that the response to fasting is driven by increased vagal efferent tone. The dissociation between nutrient load- and deprivation-related ghrelin responses indicates that the regulation of circulating ghrelin levels involves separate mechanisms operating through anatomically distinct pathways.
血浆胃饥饿素水平对短期和长期营养波动有反应，随食物摄入而迅速下降，随食物剥夺或体重减轻而升高。我们假设迷走神经参与了这两种反应。与营养相关的胃饥饿素抑制可能由胃肠道负荷相关的迷走神经传入活动介导，或取决于迷走神经传出纤维向大多数胃饥饿素产生部位的前肠的输入。同样，剥夺诱导的胃饥饿素升高可能需要与状态相关的迷走神经传入或传出活动。在这里，我们通过在48小时食物剥夺期间以及液体饮食胃内灌注前后，对膈下迷走神经切断术大鼠和假手术对照组大鼠进行采血，研究了迷走神经在血浆胃饥饿素调节中的作用。迷走神经切断术既不影响基线胃饥饿素水平，也不影响营养负荷对胃饥饿素的抑制作用。然而，膈下迷走神经切断术完全阻止了食物剥夺诱导的血浆胃饥饿素水平升高（约为基线水平的160%）。在另一个实验中，硝酸甲基阿托品治疗显著降低了与剥夺相关的血浆胃饥饿素升高，表明对禁食的反应是由迷走神经传出张力增加驱动的。营养负荷和剥夺相关的胃饥饿素反应之间的分离表明，循环胃饥饿素水平的调节涉及通过解剖学上不同的途径运作的不同机制。
