The Function of Mammalian LPGAT1

哺乳动物LPGAT1的功能

基本信息

项目摘要

Project Summary/Abstract Disorders of fat metabolism, such as obesity, metabolic syndrome, and atherosclerosis, are characterized by abnormal processing of fatty acids. The non-random distribution of fatty acids in phospholipids, where saturated chains are linked to the first (sn-1) but unsaturated chains are linked to the second (sn-2) carbon atom of the glycerol group, has important implications for membrane structure, lipid metabolism, and second messenger functions. However, while the composition of unsaturated fatty acids in sn-2 position is controlled by the Lands pathway, it has remained unclear what controls saturated fatty acids in sn-1 position. We have collected preliminary data that strongly suggest an sn-1 specific remodeling pathway for saturated fatty acids, which plays a pivotal role in the production of lipoproteins. Based on our preliminary data we postulate that the acyltransferase LPGAT1 controls the composition of saturated fatty acids in the two most abundant phospholipids, phosphatidylethanolamine (PE) and phosphatidylcholine (PC), and that this pathway is critical for the regulation of the de novo synthesis of lipids in hepatocytes. To test our hypothesis and to identify the function of LPGAT1, we will (i) establish the mechanism of phospholipid remodeling by LPGAT1 and (ii) establish the regulatory function of LPGAT1 in lipid de novo synthesis. To this end, we will define the enzymatic reaction of LPGAT1 in vitro upon expression and purification of the enzyme (subaim 1a), determine the effect of LPGAT1 knockout and knockdown on the lipid composition of subcellular membranes by lipidomics analysis of tissues and organelles (subaim 1b), dissect the remodeling pathway of LPGAT1 by tracing the metabolism of isotope-labeled substrates and by reconstituting the deacylation-reacylation cycle (subaim 1c), determine the mechanism by which LPGAT1 remodels PC by isotope labeling studies in hepatocytes (subaim 1d), determine how LPGAT1 affects global lipid fluxes in mice by lipidome-wide 13C- fluxomics analysis (subaim 2a); determine the effect of LPGAT1 ablation on lipoprotein metabolism by measuring production and clearance of lipoproteins in mice (subaim 2b), and establish whether LPGAT1 ablation protects from atherosclerosis in LDL-receptor deficient mice (subaim 2c). The proposed work is significant because (i) it will establish a parallel concept to the Lands cycle for the remodeling of saturated fatty acids in sn-1 position and (ii) it will identify the function of this pathway within the lipid metabolic network. This is expected to have critical influence on the evolving concepts of phospholipid remodeling and be directly relevant to prevalent health problems, such as obesity, metabolic syndrome, and atherosclerosis.
项目总结/文摘

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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M Mahmood Hussain其他文献

Nutrition & Metabolism Classics: a disconnect between highly cited and highly accessed articles
  • DOI:
    10.1186/1743-7075-11-13
  • 发表时间:
    2014-03-19
  • 期刊:
  • 影响因子:
    4.100
  • 作者:
    M Mahmood Hussain;Lucy Abel;Ahmed Bakillah
  • 通讯作者:
    Ahmed Bakillah
Plasminogen Activator Inhibitor-1 and Tissue-Plasminogen Activator in Minority Adolescents with Type 2 Diabetes and Obesity
患有 2 型糖尿病和肥胖的少数民族青少年中纤溶酶原激活剂抑制剂 1 和组织纤溶酶原激活剂
  • DOI:
  • 发表时间:
    2005
  • 期刊:
  • 影响因子:
    3.6
  • 作者:
    Vatcharapan Umpaichitra;M Mahmood Hussain;S. Castells
  • 通讯作者:
    S. Castells
Acknowledgement of manuscript reviewers the underappreciated contributors
  • DOI:
    10.1186/s12986-016-0078-x
  • 发表时间:
    2016-03-02
  • 期刊:
  • 影响因子:
    4.100
  • 作者:
    Ahmed Bakillah;M Mahmood Hussain
  • 通讯作者:
    M Mahmood Hussain

M Mahmood Hussain的其他文献

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{{ truncateString('M Mahmood Hussain', 18)}}的其他基金

Administrative Core
行政核心
  • 批准号:
    10628986
  • 财政年份:
    2023
  • 资助金额:
    $ 51.66万
  • 项目类别:
Biogenesis and Catabolism of Atherogenic Lipoproteins
致动脉粥样硬化脂蛋白的生物发生和分解代谢
  • 批准号:
    10628985
  • 财政年份:
    2023
  • 资助金额:
    $ 51.66万
  • 项目类别:
Regulation of plasma LDL and HDL by microRNA-541-3p
microRNA-541-3p 对血浆 LDL 和 HDL 的调节
  • 批准号:
    10733641
  • 财政年份:
    2023
  • 资助金额:
    $ 51.66万
  • 项目类别:
Adipose MTP and FIT2 in the regulation of plasma lipids, obesity and atherosclerosis
脂肪MTP和FIT2在血脂、肥胖和动脉粥样硬化调节中的作用
  • 批准号:
    10628990
  • 财政年份:
    2023
  • 资助金额:
    $ 51.66万
  • 项目类别:
Role of Lipoprotein Assembly in Maternal-Fetal Transport of Beta-Carotene
脂蛋白组装在 β-胡萝卜素母胎转运中的作用
  • 批准号:
    10642665
  • 财政年份:
    2019
  • 资助金额:
    $ 51.66万
  • 项目类别:
Role of Lipoprotein Assembly in Maternal-Fetal Transport of Beta-Carotene
脂蛋白组装在 β-胡萝卜素母胎转运中的作用
  • 批准号:
    10390463
  • 财政年份:
    2019
  • 资助金额:
    $ 51.66万
  • 项目类别:
Role of Lipoprotein Assembly in Maternal-Fetal Transport of Beta-Carotene
脂蛋白组装在 β-胡萝卜素母胎转运中的作用
  • 批准号:
    9913384
  • 财政年份:
    2019
  • 资助金额:
    $ 51.66万
  • 项目类别:
MicroRNAs regulating plasma LDL and HDL
MicroRNA 调节血浆 LDL 和 HDL
  • 批准号:
    10266009
  • 财政年份:
    2018
  • 资助金额:
    $ 51.66万
  • 项目类别:
Effects of miR-30c deficiency on plasma cholesterol and atherosclerosis
miR-30c 缺陷对血浆胆固醇和动脉粥样硬化的影响
  • 批准号:
    10424970
  • 财政年份:
    2017
  • 资助金额:
    $ 51.66万
  • 项目类别:
Effects of miR-30c deficiency on plasma cholesterol and atherosclerosis
miR-30c 缺陷对血浆胆固醇和动脉粥样硬化的影响
  • 批准号:
    9401363
  • 财政年份:
    2017
  • 资助金额:
    $ 51.66万
  • 项目类别:

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Medium-chain acyl-coenzyme A dehydrogenase as an essential feeder of glioblastoma multiforme
中链酰基辅酶 A 脱氢酶作为多形性胶质母细胞瘤的重要饲养者
  • 批准号:
    10094200
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中链酰基辅酶 A 脱氢酶作为多形性胶质母细胞瘤的重要饲养者
  • 批准号:
    10335175
  • 财政年份:
    2018
  • 资助金额:
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  • 项目类别:
Molecular Biology of Acyl-coenzyme A : cholesterol Acyltransferase
酰基辅酶 A 的分子生物学:胆固醇酰基转移酶
  • 批准号:
    08044304
  • 财政年份:
    1996
  • 资助金额:
    $ 51.66万
  • 项目类别:
    Grant-in-Aid for international Scientific Research
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