Hypoadiponectinemia and Gestational Diabetes

低脂联素血症和妊娠期糖尿病

基本信息

  • 批准号:
    10063518
  • 负责人:
  • 金额:
    $ 38.75万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2017
  • 资助国家:
    美国
  • 起止时间:
    2017-12-01 至 2022-11-30
  • 项目状态:
    已结题

项目摘要

Gestational diabetes mellitus (GDM) is getting more attention due to its high prevalence and adverse effects on gestational outcomes and offspring health in later life. Obesity is a key risk factor of GDM. Adipose tissue is not only metabolically active but also an endocrine organ. Adiponectin is an adipocyte-secreted hormone that improves glucose and lipid metabolism. Hypoadiponectinemia is widely observed in GDM and/or pregnant women with obesity. More importantly, human studies have demonstrated that hypoadiponectinemia before pregnancy and during the first and second trimesters strongly predicts GDM in later pregnancy. However, there is no experimental evidence verifying the causal relationship between hypoadiponectinemia and GDM. By crossing adiponectin gene knockout (Adipoq-/-) and wild-type (WT) mice, we recently created pregnant mouse models with or without adiponectin deficiency while all fetuses were genetically identical. Despite no difference in maternal body weight and adiposity, the main hallmarks of GDM, including glucose intolerance, hyperlipidemia, insulin insufficiency and increased fetal body weight, were observed in Adipoq-/- dams at late pregnancy. Viral vector-mediated adiponectin reconstitution attenuated these metabolic phenotypes in Adipoq-/- dams. Interestingly, no significant decrease in insulin sensitivity was detected in either peripheral tissues or liver of Adipoq-/- dams. However, low levels of blood insulin and reduced β-cell mass were detected in Adipoq-/- dams. Most importantly, the above described metabolic defects were not observed in virgin Adipoq-/- mice. Our preliminary studies suggested that adiponectin enhances prolactin-induced β-cell proliferation by increasing tryptophan hydroxylase 1 (TPH1) gene transcription and serotonin expression. Therefore, the available information and our preliminary data led us to hypothesize that adiponectin plays an important role in pregnancy-induced compensatory β-cell expansion by enhancing TPH1/serotonin pathway. Hypoadiponectinemia impairs maternal glucose and lipid metabolism through inadequate β-cell expansion and insulin insufficiency. A series of mouse studies is proposed under 2 specific aims. Specific aim 1 will determine the role of adiponectin in pregnancy-induced adaptive β-cell expansion and if hypoadiponectinemia impairs maternal metabolism through insulin insufficiency. Specific aim 2 will investigate the underlying mechanisms through which adiponectin enhances pregnancy-induced β-cell expansion. The expected results of this proposal will demonstrate the causal role of hypoadiponectinemia in the development of metabolic defects during pregnancy. The anticipated success of this project will have a significant impact on the research of maternal metabolic adaptation during normal pregnancy and GDM.
妊娠期糖尿病(GDM)由于其高患病率和高并发症, 对妊娠结局和后代晚年健康的不良影响。肥胖是一个关键风险 GDM因素。脂肪组织不仅具有代谢活性,而且是一种内分泌器官。 脂联素是一种脂肪细胞分泌的激素,可改善糖脂代谢。 低脂联素血症广泛见于GDM和/或妊娠期肥胖妇女。更重要的是, 人体研究表明,在怀孕前和第一次, 妊娠中期强烈预测妊娠后期GDM。 然而,没有实验证据证实 低脂联素血症和GDM。通过将脂联素基因敲除(Adipoq-/-)和野生型(WT) 小鼠,我们最近建立了有或没有脂联素缺乏的怀孕小鼠模型, 胎儿的基因完全相同 尽管母体体重和肥胖没有差异,但GDM的主要特征,包括 葡萄糖不耐症、高脂血症、胰岛素不足和胎儿体重增加, 在妊娠晚期的Adipoq-/-母鼠中观察到。病毒载体介导的脂联素重建 减弱了Adipoq-/-母鼠的这些代谢表型。有趣的是, 在Adipoq-/-母鼠的外周组织或肝脏中检测到胰岛素敏感性。然而,在这方面, 在Adipoq-/-母鼠中检测到低水平的血液胰岛素和减少的β-细胞质量。最 重要的是,在未交配的Adipoq-/-小鼠中没有观察到上述代谢缺陷。我们 初步研究表明,脂联素通过以下途径增强催乳素诱导的β细胞增殖: 增加色氨酸羟化酶1(TPH 1)基因转录和5-羟色胺表达。 因此,现有的信息和我们的初步数据使我们假设, 脂联素在妊娠诱导的代偿性β细胞扩增中起重要作用, TPH 1/5-羟色胺通路。低脂联素血症通过以下途径损害母体糖和脂质代谢: β细胞扩增不足和胰岛素不足。一系列小鼠研究被提议在 2具体目标具体目标1将确定脂联素在妊娠诱导 适应性β细胞扩增和低脂联素血症是否通过胰岛素损害母体代谢 不足。具体目标2将研究脂联素通过以下机制 增强妊娠诱导的β细胞扩增。该提案的预期结果将表明, 低脂联素血症在妊娠期间代谢缺陷发展中的因果作用。 该项目的预期成功将对孕产妇死亡的研究产生重大影响。 正常妊娠和GDM期间的代谢适应。

项目成果

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Jianhua Shao其他文献

Jianhua Shao的其他文献

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{{ truncateString('Jianhua Shao', 18)}}的其他基金

Pancreatic alpha-cells and Maternal metabolic Adaptation
胰腺α细胞和母体代谢适应
  • 批准号:
    10681909
  • 财政年份:
    2023
  • 资助金额:
    $ 38.75万
  • 项目类别:
Alpha cell-derived Extracellular Vesicles and Maternal Insulin Production
α细胞来源的细胞外囊泡和母体胰岛素的产生
  • 批准号:
    10681939
  • 财政年份:
    2023
  • 资助金额:
    $ 38.75万
  • 项目类别:
Brown adipose tissue development and fetal growth
棕色脂肪组织发育和胎儿生长
  • 批准号:
    10539636
  • 财政年份:
    2022
  • 资助金额:
    $ 38.75万
  • 项目类别:
Brown adipose tissue development and fetal growth
棕色脂肪组织发育和胎儿生长
  • 批准号:
    10687215
  • 财政年份:
    2022
  • 资助金额:
    $ 38.75万
  • 项目类别:
Hypoadiponectinemia and Gestational Diabetes
低脂联素血症和妊娠期糖尿病
  • 批准号:
    10753827
  • 财政年份:
    2017
  • 资助金额:
    $ 38.75万
  • 项目类别:
The maternal-fetal adiponectin differential and fetal fat deposition
母胎脂联素差异和胎儿脂肪沉积
  • 批准号:
    8900277
  • 财政年份:
    2012
  • 资助金额:
    $ 38.75万
  • 项目类别:
Adiponectin and fetal programming
脂联素和胎儿编程
  • 批准号:
    8431780
  • 财政年份:
    2012
  • 资助金额:
    $ 38.75万
  • 项目类别:
Adiponectin and fetal programming
脂联素和胎儿编程
  • 批准号:
    8610337
  • 财政年份:
    2012
  • 资助金额:
    $ 38.75万
  • 项目类别:
Adiponectin and fetal programming
脂联素和胎儿编程
  • 批准号:
    8235753
  • 财政年份:
    2012
  • 资助金额:
    $ 38.75万
  • 项目类别:
The maternal-fetal adiponectin differential and fetal fat deposition
母胎脂联素差异和胎儿脂肪沉积
  • 批准号:
    8708063
  • 财政年份:
    2012
  • 资助金额:
    $ 38.75万
  • 项目类别:

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Recruitment of brown adipocytes in visceral white adipose tissue by fibroblast growth factor 8b
成纤维细胞生长因子 8b 将棕色脂肪细胞募集到内脏白色脂肪组织中
  • 批准号:
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Enhancing Energy Expending Adipocytes in White Adipose Tissue
增强白色脂肪组织中的能量消耗脂肪细胞
  • 批准号:
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  • 财政年份:
    2014
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Induction of brown-like adipocytes in white adipose tissue by food-derived factors
食物源性因子在白色脂肪组织中诱导棕色样脂肪细胞
  • 批准号:
    26450168
  • 财政年份:
    2014
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  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
WAT-on-a-chip - Development of a micofluidic, microphysiologic in vitro adipose tissue model for high-throughput drug screening based on hiPSC-derived adipocytes.
WAT-on-a-chip - 开发微流体、微生理体外脂肪组织模型,用于基于 hiPSC 衍生脂肪细胞的高通量药物筛选。
  • 批准号:
    257256526
  • 财政年份:
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Enhancing Energy Expending Adipocytes in White Adipose Tissue
增强白色脂肪组织中的能量消耗脂肪细胞
  • 批准号:
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  • 财政年份:
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Enhancing Energy Expending Adipocytes in White Adipose Tissue
增强白色脂肪组织中的能量消耗脂肪细胞
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    8520690
  • 财政年份:
    2013
  • 资助金额:
    $ 38.75万
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Enhancing Energy Expending Adipocytes in White Adipose Tissue
增强白色脂肪组织中的能量消耗脂肪细胞
  • 批准号:
    8629741
  • 财政年份:
    2013
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Effect of exercise training on formation of brite adipocytes within white adipose tissue
运动训练对白色脂肪组织内脂肪细胞形成的影响
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    23700778
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    2011
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Investigation for the mechanisms of the emergence of brown adipocytes in white adipose tissue
白色脂肪组织中棕色脂肪细胞出现机制的研究
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    21780261
  • 财政年份:
    2009
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LOUISIANA COBRE: P1: INDUCE THERMOGENIC BROWN ADIPOCYTES IN WHITE ADIPOSE TISSUE
路易斯安那 COBRE:P1:在白色脂肪组织中诱导产热棕色脂肪细胞
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    7610781
  • 财政年份:
    2007
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