LIPID METABOLISM BY NMR

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 该应用的长期目标是了解硬脂酰辅酶A去饱和酶在新陈代谢中的作用。硬脂酰辅酶A脱饱和酶(SCD)是脂肪合成的关键调节因子，催化合成单不饱和脂肪酸(MUFA)，主要是油酰辅酶A(18：1n9)和棕榈油酰辅酶A(16：1n7)。在人类和啮齿动物肥胖和胰岛素抵抗状态下，SCD的表达增加，这表明过度的18：1n9或16：1n7合成可能有助于代谢性疾病的发展。SCD1亚型全球缺失的小鼠对饮食和遗传导致的肥胖、胰岛素抵抗和肝脏脂肪变性具有显著的抵抗力。在这个项目中，我们将重点关注两个目标。在目标1中，我们将确定肝脏SCD1表达在内质网应激反应和内质网应激介导的脂肪生成中的作用。在目标2中，我们将确定由于SCD1缺乏而导致内质网应激的机制。由于代谢综合征疾病的主要代谢罪魁祸首是脂类，了解硬脂酰辅酶A去饱和酶基因在肝脏代谢和内质网应激途径中的作用可能会提供重要的见解

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The long-term goal of this application is to understand the role of stearoyl-CoA desaturase in metabolism. Stearoyl-CoA desaturase (SCD) is a critical regulator of lipogenesis that catalyzes the synthesis of monounsaturated fatty acids (MUFA), mainly oleoyl- (18:1n9) and palmitoleoyl-CoA (16:1n7). SCD expression is elevated in human and rodent obese and insulin resistant states, suggesting that excess 18:1n9 or 16:1n7 synthesis may contribute to metabolic disease development. Mice with a global deletion of the SCD1 isoform are remarkably resistant to diet- and genetically-induced obesity, insulin resistance and liver steatosis. In this project we will focus on two aims. In Aim 1, we will determine the contribution of hepatic SCD1 expression to the ER stress response and ER stress-mediated lipogenesis. In Aim 2, we will determine the mechanisms causing ER stress due to SCD1 deficiency. As the main metabolic culprits in diseases of the metabolic syndrome are lipids, understanding the role of stearoyl-CoA desaturase genes in hepatic metabolism and ER stress pathways might provide major insights