Direct gut to pancreas neuronal communication in the regulation of metabolism

你吃什么对健康和不健康有很大影响。人体每天消耗的食物在肠道中分解成一种复杂的分子混合物。这些分子在肠道中被感觉到，以调节代谢功能。它们不仅有助于调节消化，还有助于调节全身的过程，包括身体如何调节葡萄糖，以及如何处理脂肪和蛋白质。新的科学工具首次使我们能够从分子水平上了解这些食物成分是如何影响新陈代谢和健康的。胰腺是一个特别重要的代谢器官，在消化、碳水化合物、脂肪和蛋白质代谢中起着关键作用。保持良好的胰腺功能对于在整个生命过程中保持健康至关重要。胰腺位于小肠的上部，这部分被称为十二指肠。近50年前，人们发现有神经元起源于十二指肠壁并延伸到胰腺，这表明肠道可以通过这一途径直接向胰腺发出信号，以快速调整胰腺功能和新陈代谢，以响应食物。然而，随后，对这些神经元的研究很少。我们的初步数据显示，这些神经元的一个亚群参与了特定脂肪可以改善对葡萄糖的代谢反应的途径。然而，在这条通路中还有许多几乎完全没有特征的其他神经元。我们将在小鼠模型中映射从肠道到胰腺的神经元信号，并建立与食物相关的分子来调节它们的功能。我们将在老鼠体内操纵这些神经元，以确定它们对新陈代谢的影响，以及它们是否可以同步胰腺不同部分的活动，从而对身体产生更大的影响。这些研究将确定这些神经元在未来是否可以有效地通过特殊饮食来改善长期健康。

What you eat plays a major role in health and ill health. Every day the body consumes foods which are broken down in the gut into a complex mixture of molecules. These molecules are sensed in the gut to modulate metabolic functions. They help to regulate digestion but also body wide processes, including how the body regulates glucose, and how it processes fat and protein. New scientific tools are for the first time allowing us to understand how these food components affect metabolism and health on a molecular level. The pancreas is a particularly important metabolic organ, with critical roles in digestion, and in carbohydrate, fat and protein metabolism. Maintaining good pancreatic function is vital to maintaining health across the life course. The pancreas sits next to the upper part of the small intestine, which is called the duodenum. Almost fifty years ago it was discovered that there are neurons that originate in the wall of the duodenum which extend to the pancreas, suggesting that the gut could signal directly to the pancreas via this pathway to rapidly adjust pancreatic function and metabolism in response to food. However, subsequently, these neurons have been little studied. Our pilot data shows that a subpopulation of these neurons is involved in the pathway by which specific fats can improve the metabolic response to glucose. However, there are many other neurons in this pathway which are almost completely uncharacterised. We will map the neurons signalling from the gut to the pancreas in a mouse model, and establish the food-related molecules that regulate their function. We will manipulate these neurons in mice to determine the effects they have on metabolism, and whether they can synchronise the activity of different parts of the pancreas to have even greater effects on the body. These studies will determine whether in the future these neurons can be usefully targeted by special diets to improve long term health.