Lipid Metabolism in Pregnancy: Adipose-Placental Interactions

妊娠期脂质代谢:脂肪-胎盘相互作用

基本信息

  • 批准号:
    BB/X007758/1
  • 负责人:
  • 金额:
    $ 70.87万
  • 依托单位:
  • 依托单位国家:
    英国
  • 项目类别:
    Research Grant
  • 财政年份:
    2023
  • 资助国家:
    英国
  • 起止时间:
    2023 至 无数据
  • 项目状态:
    未结题

项目摘要

Viviparity, or the development of live young within the body of the parent, is a fundamental biological process that is used by mammals to protect their offspring during the vunerable period of early life. In order to support viviparity mammals have evolved a host of mechanisms to allow the efficient transfer of nutrition from mother to offspring. A crucial adaptation was the evolution of the placenta. The placenta is a transient organ with multiple functions that ultimately support pregnancy. In the placenta the maternal and fetal blood come into close proximity, allowing the exchange of nutrients and waste products. In addition, the placenta produces hormones that signal to the mother's body and direct the nutrients that she obtains from food toward the fetus.Pregnancy in mammals is thought to comprise of two phases; early pregnancy when the mother increases her appetite in order to store energy in her fat depots, and late pregnancy when she releases this energy and nutrients toward the rapidly growing fetus. Some nutrients are in particularly high demand by the developing fetus. One class of these nutrients are the essential fatty acids (EFAs). EFAs come into the body in the diet, they are particularly abundant in marine life, and they cannot be synthesised by mammals. These fatty acids are necessary for the development and growth of the brain and eye. Lack of these nutrients in the maternal diet causes blindness and neurodevelopmental disorders in humans. Because they are so important, EFAs are preferentially transported to the developing fetus during pregnancy. However, we currently do not understand how the mother achieves this, nor how EFAs cross the placental barrier to enter the fetal circulation so they can be used to build the brain and eye. In this project we hope to explain how EFAs travel from the maternal diet to the fetus. We suspect that EFAs are stored in maternal fat stores even prior to pregnancy, and that in the second half of pregnancy they are selectively released and travel to the liver where they are packaged into a form that can be recognised by placental cells. At the placental barrier we think that the EFAs are recognised by a specific transporter molecule that can move them inside the cells. The final part of the project will investigate how the placenta communicates with the mother so that she releases fats from her fat stores. We believe that specific placental hormones signal directly to the maternal fat to allow the energy and nutrients there to be liberated at the best time to support fetal growth.It is important to understand how fatty acids, including EFAs, are transferred from mother to fetus for several reasons. Firstly, this is a fundamental biological process that underlies all mammalian reproduction, from human pregnancy to livestock farming. Secondly, many women are poorly nourished and this becomes more important during pregnancy when the mother may have insufficient nutrient stores to support the healthy development of the baby. Many intervention strategies have tried to increase the amount of EFAs given to malnourished mothers in pregnancy to try to improve the health of the baby. However, these trials have met with mixed success. In order to fully support healthy pregnancy, early life and lifelong health, we need to understand much more about the processes by which the placenta and mother communicate to ensure adequate nutrient flow.
胎生(Viviparity),即在母体体内孕育幼体,是一种基本的生物学过程,哺乳动物用它来保护幼仔在生命早期的脆弱时期。为了支持胎生,哺乳动物已经进化出一系列机制,使营养从母亲有效地转移到后代。一个关键的适应是胎盘的进化。胎盘是一个短暂的器官,具有多种功能,最终支持怀孕。在胎盘中,母体和胎儿的血液接近,允许营养物质和废物的交换。此外,胎盘产生激素,向母亲的身体发出信号,并将她从食物中获得的营养引导给胎儿。哺乳动物的怀孕被认为包括两个阶段;怀孕初期,母亲增加食欲,以便在脂肪库中储存能量;怀孕后期,母亲将这些能量和营养物质释放给快速成长的胎儿。发育中的胎儿对某些营养素的需求量特别高。其中一类营养素是必需脂肪酸(EFAs)。EFAs通过饮食进入人体,它们在海洋生物中含量特别丰富,哺乳动物无法合成。这些脂肪酸对大脑和眼睛的发育和生长是必需的。母亲饮食中缺乏这些营养素会导致人类失明和神经发育障碍。因为它们非常重要,所以在怀孕期间EFAs会优先被运送到发育中的胎儿体内。然而,我们目前还不知道母亲是如何做到这一点的,也不知道EFAs是如何穿过胎盘屏障进入胎儿循环的,这样它们就可以用来构建大脑和眼睛。在这个项目中,我们希望解释EFAs是如何从母体的饮食传递给胎儿的。我们怀疑EFAs甚至在怀孕前就储存在母体脂肪中,在怀孕的后半段,它们被选择性地释放并运输到肝脏,在那里它们被包装成一种可以被胎盘细胞识别的形式。在胎盘屏障处,我们认为EFAs被一种特定的转运分子识别,可以将它们转移到细胞内。该项目的最后一部分将研究胎盘如何与母亲沟通,从而使她从储存的脂肪中释放脂肪。我们认为,特定的胎盘激素直接向母体脂肪发出信号,使能量和营养物质在最佳时间被释放出来,以支持胎儿的生长。了解脂肪酸,包括EFAs,是如何从母亲转移到胎儿的,这是很重要的,有几个原因。首先,这是一个基本的生物学过程,是所有哺乳动物繁殖的基础,从人类怀孕到畜牧业。其次,许多妇女营养不良,这在怀孕期间变得更加重要,因为母亲可能没有足够的营养储备来支持婴儿的健康发育。许多干预策略都试图增加营养不良母亲在怀孕期间的EFAs剂量,以改善婴儿的健康。然而,这些试验成败参半。为了充分支持健康的怀孕、早期生活和终身健康,我们需要更多地了解胎盘和母亲沟通以确保充足营养流动的过程。

项目成果

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Marika Charalambous其他文献

Mapping regulatory elements at the DLK1 locus involved in the pathogenesis of human fetal growth restriction
  • DOI:
    10.1016/j.placenta.2023.07.240
  • 发表时间:
    2023-09-07
  • 期刊:
  • 影响因子:
  • 作者:
    Maria Lillina Vignola;Bertille Montibus;Valeria Scagliotti;Rebecca Oakey;Alan Hodgkinson;Marika Charalambous
  • 通讯作者:
    Marika Charalambous
Single-cell RNA sequencing of the maternal hypothalamus reveals a distinct neuroendocrine transcriptome in pregnancy.
  • DOI:
    10.1016/j.placenta.2023.07.134
  • 发表时间:
    2023-09-07
  • 期刊:
  • 影响因子:
  • 作者:
    Risha Amarsi;Benjamin Jones;Pawan Dhami;Thea Willis;Marika Charalambous
  • 通讯作者:
    Marika Charalambous
Placental expression of Delta-like homologue 1 (Dlk1) regulates endothelial cell development and hormone production to modulate fetal growth and maternal fatty acid metabolism
  • DOI:
    10.1016/j.placenta.2023.07.204
  • 发表时间:
    2023-09-07
  • 期刊:
  • 影响因子:
  • 作者:
    Valeria Scagliotti;Maria Vignola;Ruben Esse;Marika Charalambous
  • 通讯作者:
    Marika Charalambous

Marika Charalambous的其他文献

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{{ truncateString('Marika Charalambous', 18)}}的其他基金

Imprinted gene expression in early life determines body composition and response to the obesogenic environment.
生命早期的印记基因表达决定了身体成分和对肥胖环境的反应。
  • 批准号:
    MR/S00002X/1
  • 财政年份:
    2019
  • 资助金额:
    $ 70.87万
  • 项目类别:
    Research Grant
Investigating a novel molecular diagnostic tool for identification and stratification of pregnancy complications
研究一种用于妊娠并发症识别和分层的新型分子诊断工具
  • 批准号:
    MR/R022836/1
  • 财政年份:
    2018
  • 资助金额:
    $ 70.87万
  • 项目类别:
    Research Grant
Communication between mother and fetus : Imprinting and endocrine adaptations to pregnancy
母亲和胎儿之间的交流:妊娠印记和内分泌适应
  • 批准号:
    MR/L002345/2
  • 财政年份:
    2017
  • 资助金额:
    $ 70.87万
  • 项目类别:
    Research Grant
Communication between mother and fetus : Imprinting and endocrine adaptations to pregnancy
母亲和胎儿之间的交流:妊娠印记和内分泌适应
  • 批准号:
    MR/L002345/1
  • 财政年份:
    2014
  • 资助金额:
    $ 70.87万
  • 项目类别:
    Research Grant

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Placental lipid metabolism impacts fetal adiposity and is programmed by the maternal metabolic milieu in early pregnancy
胎盘脂质代谢影响胎儿肥胖,并受妊娠早期母体代谢环境影响
  • 批准号:
    9397888
  • 财政年份:
    2017
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Placental lipid metabolism impacts fetal adiposity and is programmed by the maternal metabolic milieu in early pregnancy
胎盘脂质代谢影响胎儿肥胖,并受妊娠早期母体代谢环境影响
  • 批准号:
    10201689
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    $ 70.87万
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妊娠期环境因素通过表观遗传修饰对儿童脂质代谢和生长发育的影响
  • 批准号:
    16K19245
  • 财政年份:
    2016
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    $ 70.87万
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    Grant-in-Aid for Young Scientists (B)
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孕期母体营养对子代脂质代谢包括脂质吸收的影响
  • 批准号:
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  • 财政年份:
    2015
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肝脏和内脏脂肪在妊娠期糖脂代谢中的作用
  • 批准号:
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  • 财政年份:
    2014
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    $ 70.87万
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Role of liver and visceral fat in glucose and lipid metabolism during pregnancy
肝脏和内脏脂肪在妊娠期糖脂代谢中的作用
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  • 财政年份:
    2014
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    $ 70.87万
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肝脏和内脏脂肪在妊娠期糖脂代谢中的作用
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  • 财政年份:
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LIPID METABOLISM IN PREGNANCY AND WITH PREECLAMPSIA
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