Role of lysophosphatidylcholine acyltransferases on adipose tissue expansion and Metabolic Syndrome

溶血磷脂酰胆碱酰基转移酶对脂肪组织扩张和代谢综合征的作用

• 批准号: 2113481
• 金额: --
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2113481
• 关键词: Role; lysophosphatidylcholine; acyltransferases; adipose; tissue

White adipose tissue (WAT) is an endocrine organ specialized in storing/mobilising energy as lipids. In response to positive energy balance, adipocytes need to grow in number and size, but this capacity is limited. When WAT cannot further expand (i.e., severe obesity or even in lipodystrophic phenotypes), the excess of nutrients cannot be efficiently stored and lipids and spill over to other tissues such as liver, pancreas and muscle, known as lipotoxicity. This leads to severe metabolic complications including insulin resistance, diabetes, NAFLD and cardiovascular disease. Healthy function of adipocytes requires the dynamic biosynthesis and remodelling of glycerophospholipids, one of the major constituents of the plasma membrane. The Lands cycle is responsible for the remodelling of glycerophospholipids and ensures their asymmetry and diversity, through a concerted action of enzymes including phospholipases (PLA2) and a variety of Lysophosphatidylacyltransferases (LPLATs). Specifically, LPLATs are responsible for the incorporation of specific mono/polyunsaturated fatty acids into the sn2 moiety of lysophospholipids. Growing body of evidence suggests that LPLATs play an essential role in the pathophysiology of several metabolic organs such as the liver and intestine, but there is still little information regarding their role in WAT expansion. This project aims to identify the functional relevance of these enzymes in the context of adipose tissue expansion during positive energy balance, by using genetically modified models, in vitro systems and system biology approaches.Increasing our understanding of how perturbation in the expression/activity of those enzymes relate to metabolic complications may open new avenues of research and facilitate the development of novel therapeutic strategies against obesity and associated co-morbidities.

白色脂肪组织（WAT）是一种内分泌器官，专门储存/调动能量作为脂质。为了应对正能量平衡，脂肪细胞需要在数量和大小上增长，但这种能力是有限的。当WAT不能进一步扩展时（即，严重肥胖或甚至在脂肪营养不良表型中），过量的营养物质不能有效地储存，脂质溢出到其他组织，如肝脏、胰腺和肌肉，称为脂毒性。这会导致严重的代谢并发症，包括胰岛素抵抗、糖尿病、非酒精性脂肪肝和心血管疾病。脂肪细胞的健康功能需要甘油磷脂的动态生物合成和重塑，甘油磷脂是质膜的主要成分之一。Lands循环负责甘油磷脂的重塑，并通过包括磷脂酶（PLA 2）和多种溶血磷脂酰转移酶（LPLATs）在内的酶的协同作用确保其不对称性和多样性。具体而言，LPLATs负责将特定的单/多不饱和脂肪酸掺入溶血磷脂的sn 2部分。越来越多的证据表明，LPLATs在一些代谢器官如肝脏和肠道的病理生理学中起着重要作用，但关于它们在WAT扩张中的作用的信息仍然很少。该项目旨在通过使用转基因模型，在体外系统和系统生物学方法。增加我们的理解如何扰动的表达/与代谢并发症相关的那些酶的活性可以开辟新的研究途径，并促进针对肥胖症的新治疗策略的开发，相关合并症。