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The effect of intrauterine growth restriction on the expression of the PPARgamma target gene, Setd8 in adipose and liver of the rat.

机译:宫内生长受限对大鼠脂肪和肝脏中PPARγ靶基因Setd8表达的影响。

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摘要

Intrauterine growth restricted (IUGR) born individuals are at a higher risk for developing obesity and associated co-morbidities in adulthood. An underlying component of these morbidities is adipose dysfunction, with the accumulation of visceral adipose tissue (VAT) in conjunction with an increased expression of peroxisome proliferator activated receptor gamma PPARgamma, a proadipogenic factor. Interestingly, in hepatic tissue of the adolescent IUGR female, PPARgamma expression displays a decreasing trend. PPARgamma's actions may be mediated by set domain containing histone methyltransferase Setd8 an epigenetic modification enzyme, and direct transcriptional target of PPARgamma. In this study, we hypothesize that IUGR will affect mRNA and protein levels of Setd8 in a gender and tissue specific manner in visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and hepatic depots before the onset of metabolic disease in postnatal day 21 rats. Uteroplacental insufficiency (UPI) induced IUGR day 21 adipose (SAT and VAT), and hepatic tissue was compared to control tissue using real time RT PCR for mRNA and western blotting for protein levels of Setd8. IUGR increased Setd8 protein levels in visceral adipose tissue of males of and decreased Setd8 protein levels hepatic tissue of females. IUGR did not have a significant effect on SAT mRNA and protein levels. This study demonstrates that IUGR alters Setd8 expression in day 21 rat in a gender and tissue specific manner, consistent with previously observed changes in PPARgamma expression, before the onset of metabolic disease and obesity. We speculate that IUGR alters epigenetic gene regulation in adipose and liver, PPARgamma and its target enzyme Setd8, and that this may contribute to adult onset obesity observed in this population.
机译:宫内生长受限(IUGR)出生的个体成年后患肥胖症和相关合并症的风险较高。这些发病率的潜在组成部分是脂肪功能障碍,内脏脂肪组织(VAT)的积累与过氧化物酶体增殖物激活受体γPPARγ(促成脂因子)的表达增加有关。有趣的是,在青春期IUGR雌性的肝组织中,PPARγ表达呈下降趋势。 PPARgamma的作用可能由含有组蛋白甲基转移酶Setd8(表观遗传修饰酶)和PPARgamma的直接转录靶标的设定域介导。在这项研究中,我们假设IUGR将以性别和组织特异性的方式影响产后一天内代谢疾病发作之前内脏脂肪组织(VAT),皮下脂肪组织(SAT)和肝贮库中的Setd8的mRNA和蛋白质水平。 21只大鼠。子宫胎盘功能不全(UPI)诱导的IUGR第21天脂肪(SAT和VAT),并使用实时RT PCR检测mRNA和用Western blotting检测Setd8的蛋白质水平,比较肝组织与对照组织。 IUGR增加了男性内脏脂肪组织中Setd8蛋白的水平,降低了女性肝脏组织中Setd8蛋白的水平。 IUGR对SAT mRNA和蛋白质水平没有显着影响。这项研究表明,IUGR在代谢性疾病和肥胖症发作之前,以性别和组织特异性方式改变了21天大鼠的Setd8表达,这与先前观察到的PPARgamma表达变化有关。我们推测IUGR会改变脂肪和肝脏,PPARgamma及其靶酶Setd8中的表观遗传基因调控,并且这可能有助于在该人群中观察到成年肥胖症。

著录项

  • 作者

    Bailey, Ornela Bashaj.;

  • 作者单位

    The University of Utah.;

  • 授予单位 The University of Utah.;
  • 学科 Nutrition.
  • 学位 M.S.
  • 年度 2011
  • 页码 32 p.
  • 总页数 32
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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