Direct gut to pancreas neuronal communication in the regulation of metabolism

你吃的东西对健康和不健康起着重要作用。每天人体消耗的食物在肠道中被分解成复杂的分子混合物。这些分子在肠道中被感知以调节代谢功能。它们不仅有助于调节消化，还能调节全身的各种过程，包括身体如何调节葡萄糖，以及如何处理脂肪和蛋白质。新的科学工具第一次让我们了解这些食物成分是如何在分子水平上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。维持良好的胰腺功能对维持生命过程中的健康至关重要。胰腺紧邻小肠的上部，称为十二指肠。大约50年前，人们发现有一些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条途径直接向胰腺发出信号，以迅速调整胰腺的功能和代谢，以应对食物。然而，随后，这些神经元很少被研究。我们的试验数据表明，这些神经元的一个亚群参与了特定脂肪改善葡萄糖代谢反应的途径。然而，在这条通路中还有许多其他的神经元几乎完全没有被描述。我们将在小鼠模型中绘制从肠道到胰腺的神经元信号，并建立调节其功能的食物相关分子。我们将操纵老鼠体内的这些神经元，以确定它们对新陈代谢的影响，以及它们是否能同步胰腺不同部位的活动，从而对身体产生更大的影响。这些研究将决定未来这些神经元是否可以通过特殊饮食来有效地改善长期健康。

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.