The role of phosphatidylserine-decarboxylase for brown adipose tissue formation and function

磷脂酰丝氨酸脱羧酶对棕色脂肪组织形成和功能的作用

• 批准号: 446175916
• 负责人: Dr. Josef Ecker
• 金额: --
• 依托单位: Institut für Klinische Chemie und Laboratoriumsmedizin
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/446175916?language=en
• 关键词: role; phosphatidylserine; decarboxylase; brown; adipose

Mammalian adipose tissue can be categorized in white and brown adipose tissue (BAT). Brown adipocytes contain several small lipid droplets and can generate heat to maintain a stable body temperature by non-shivering thermogenesis, which is mediated by uncoupling protein 1 (UCP1) located in the inner mitochondrial membrane. Because substrates for BAT thermogenesis are glucose and free fatty acids, BAT is involved in systemic glucose and lipid homeostasis. Indeed, the presence and activity of human BAT correlates with higher energy expenditure, lower adiposity, and reduced risk of insulin resistance. Therefore, activation of brown adipocyte thermogenesis is considered a promising strategy to increase energy expenditure. Further, the identification of mechanisms regulating brown adipocyte development and thermogenesis might be useful to combat metabolic pathologies and diseases.We and others have previously shown that the membrane lipid composition is precisely controlled on the cellular and subcellular level, cell type-specific and adapted to cellular functions. The lipid composition of membranes significantly influences physical membrane properties including lipid packing density and fluidity. The endoplasmic reticulum (ER) is the prime organelle involved in phospholipid synthesis, followed by the Golgi apparatus and mitochondria. A significant fraction of cellular phosphatidylethanolamine (PE), a major cell membrane lipid, is generated from phosphatidylserine (PS) by phosphatidylserine-decarboxylase (PISD) in mitochondria.Because in our preliminary data PISD activity correlates with murine adipose tissue browning and UCP1-mediated respiration in brown adipocytes, we propose that PlSD is a key regulator of mitochondrial bioenergetics in BAT. Therefore, the main objectives of the proposed research program are to investigate the physiological and pathophysiological relevance of PISD for non-shivering thermogenesis in vivo as well as to identify the mechanism underlying PISD-mediated regulation of mitochondrial bioenergetics.

哺乳动物脂肪组织可分为白色和棕色脂肪组织（BAT）。棕色脂肪细胞含有几个小的脂滴，可以通过非颤抖性产热产生热量来维持稳定的体温，这是由位于线粒体内膜的解偶联蛋白1（UCP1）介导的。因为BAT产热的底物是葡萄糖和游离脂肪酸，所以BAT参与全身葡萄糖和脂质稳态。事实上，人类BAT的存在和活性与较高的能量消耗、较低的肥胖和降低的胰岛素抵抗风险相关。因此，激活棕色脂肪细胞产热被认为是一种有前途的策略，以增加能量消耗。此外，棕色脂肪细胞的发育和产热调节机制的鉴定可能有助于对抗代谢病理和疾病，我们和其他人以前已经表明，膜脂质组成是精确控制的细胞和亚细胞水平，细胞类型特异性和适应细胞功能。膜的脂质组成显著影响膜的物理性质，包括脂质堆积密度和流动性。内质网（ER）是参与磷脂合成的主要细胞器，其次是高尔基体和线粒体。一个显着的部分细胞磷脂酰乙醇胺（PE），一个主要的细胞膜脂质，产生的磷脂酰丝氨酸（PS）的磷脂酰丝氨酸脱羧酶（PISD）在mitochondrial.because在我们的初步数据PISD活性与小鼠脂肪组织布朗宁和UCP1介导的呼吸在棕色脂肪细胞，我们建议，PISD是一个关键的调节器线粒体生物能量BAT。因此，拟议的研究计划的主要目标是研究PISD在体内非颤抖性产热的生理和病理生理相关性，以及确定PISD介导的线粒体生物能量调节的机制。