Importance of intestinal phosphatidylcholine supply in regulating lipid and trimethylamine metabolism

磷脂酰胆碱（PC）对哺乳动物膜的结构完整性至关重要，是胆汁、肺表面活性剂和血浆脂蛋白中的主要磷脂。在所有有核的哺乳动物细胞中，PC都是由胆碱通过cdp -胆碱途径合成的，通过该途径的通量受CTP:phosphocholine cytidylyltransferase （CT）活性的调节。肝细胞的脂蛋白分泌需要活跃的PC生物合成。在过去的5年里，我的研究主要集中在了解膳食胆碱在调节肠道脂质代谢中的作用。本研究计划更新的长期目标是建立在我的进展势头的基础上，以阐明肠道PC供应受损对膳食脂质吸收、循环脂蛋白代谢和三甲胺产生的生理后果（微生物组产生的一种次要胆碱代谢物）。总的工作假设是，肠道PC的重新合成对正常的脂质吸收、乳糜微粒的产生和分泌至关重要。此外，我们预测当肠道供应受限时，循环脂蛋白是PC的重要来源。最后，我们假设从头合成PC调节肠道微生物组三甲胺的产生。将讨论以下具体目标：

Phosphatidylcholine (PC) is vital for the structural integrity of mammalian membranes and is the primary phospholipid in bile, lung surfactant, and plasma lipoproteins. In all nucleated mammalian cells, PC is synthesized from choline via the CDP-choline pathway, and the flux through this pathway is regulated by the activity of CTP:phosphocholine cytidylyltransferase (CT). An active PC biosynthesis is required for lipoprotein secretion from hepatocytes. During the past 5 years my NSERC-funded research has focused on understanding the role of dietary choline in regulating intestinal lipid metabolism. The long-term goal of this research program renewal is built on the momentum of my progress to elucidate the physiological consequences of impaired intestinal PC supply on dietary lipid absorption, circulating lipoprotein metabolism, and trimethylamine production (a minor choline metabolite produced by the microbiome). The overall working hypothesis is that de novo synthesis of intestinal PC is vital for normal lipid absorption, chylomicron production and secretion. Furthermore, we predict that circulating lipoproteins are a significant source of PC when intestinal supply is limiting. Finally, we hypothesize that de novo PC synthesis modulates the production of trimethylamine by the gut microbiome. The following specific aims will be addressed: