Role of lysophosphatidylcholine acyltransferases on adipose tissue expansion and Metabolic Syndrome

白色脂肪组织（WAT）是一种内分泌器官，专门用于储存/动员能量作为脂质。为了响应正能量平衡，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不能进一步扩大时（即严重肥胖甚至脂质营养不良表型），过量的营养物质不能有效储存，脂质溢出到其他组织，如肝脏、胰腺和肌肉，称为脂质毒性。这会导致严重的代谢并发症，包括胰岛素抵抗、糖尿病、NAFLD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，并通过磷脂酶（PLA2）和各种溶血磷脂酰转移酶（LPLATs）等酶的协同作用确保它们的不对称性和多样性。具体来说，LPLATs负责将特定的单/多不饱和脂肪酸结合到溶血磷脂的sn2部分中。越来越多的证据表明，LPLATs在肝脏和肠道等几个代谢器官的病理生理中起着重要作用，但关于它们在WAT扩张中的作用仍然知之甚少。该项目旨在通过使用转基因模型、体外系统和系统生物学方法，确定这些酶在正能量平衡期间脂肪组织扩张背景下的功能相关性。增加我们对这些酶的表达/活性紊乱与代谢并发症的关系的理解，可能会开辟新的研究途径，并促进针对肥胖和相关合并症的新治疗策略的发展。

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.