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首页> 外文学位 >Estrogen regulation of adiposity: In vivo and in vitro effects on adipose tissue and muscle metabolism.
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Estrogen regulation of adiposity: In vivo and in vitro effects on adipose tissue and muscle metabolism.

机译：雌激素对脂肪的调节：体内和体外对脂肪组织和肌肉代谢的影响。

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摘要

Background. Menopause is associated with an increase in adiposity along with increased risk of metabolic disease. Evidence suggests that declining levels of estrogen (E2) contribute to these changes however little is known about the molecular and biochemical mechanism by which E2 acts. Objective and specific aims. The aim of my dissertation work was to enhance our knowledge of E2's role in regulating adiposity and metabolism. To do this, I did a series of experiments, both in vivo and in vitro, examining genomic and non-genomic E2 actions on liver, muscle and adipose tissue biology. Research design and methods. To determine the effects of in vivo E2, C57/B6J mice were ovariectomized (OVX) and treated with either estrogen (E2) or control (C) subcutaneous implant pellets. Food intake was carefully controlled to eliminate the central effects of E2 on food intake. To follow-up on observations made in the in vivo studies, C2C12 myocytes and human differentiated preadipocytes (PA) were used to examine the direct effects of E2 on muscle and adipose tissue metabolism (respectively). Results. I demonstrated, for the first time, that E2 decreases adiposity and adipocyte size in OVX mice independent of changes in food intake. In addition, I identified novel genomic and non-genomic E2-dependent pathways by which E2 promotes fat oxidation, prevents TG accumulation, and enhances TG breakdown (lipolysis). This includes genomic regulation of SREBP-1c, PPAR-delta, and their downstream targets, as well as rapid activation of muscle AMP-activated protein kinase (AMPK) with E2-treatment. In vitro studies using human differentiated preadipocytes corroborate my in vivo findings on SREBP-1c expression, demonstrating E2-regulation of this lipogenic pathway. Lastly, I demonstrated a significant role for ER in adipogenesis and maintaining human adipocytes in the differentiated state. Conclusion. The results of my studies have greatly enhanced our knowledge of E2's role in adiposity and metabolism. I have identified multiple mechanisms by which E2 reduces adiposity and potentially improves metabolic health. The results of my findings have multiple implications specifically related to menopause, hormone replacement therapy, endocrine disorders which alter sex hormone levels, and the potential for gender-based medicine.
机译：背景。更年期与肥胖症增加以及代谢疾病的风险增加有关。有证据表明，雌激素（E2）水平下降是造成这些变化的原因，但人们对E2发挥作用的分子和生化机制知之甚少。目标和具体目标。我的论文工作的目的是增强我们对E2在调节肥胖和代谢中作用的认识。为此，我在体内和体外进行了一系列实验，研究了基因组和非基因组E2对肝脏，肌肉和脂肪组织生物学的作用。研究设计和方法。为了确定体内E2的作用，将C57 / B6J小鼠切除卵巢（OVX），并用雌激素（E2）或对照（C）皮下植入物小丸处理。仔细控制食物摄入量，以消除E2对食物摄入量的中心作用。为了跟进体内研究的结果，C2C12心肌细胞和人类分化的前脂肪细胞（PA）被用来分别检查E2对肌肉和脂肪组织代谢的直接作用。结果。我第一次证明了E2可以减少OVX小鼠的肥胖和脂肪细胞大小，而与食物摄入量的变化无关。此外，我确定了新的基因组和非基因组依赖E2的途径，E2通过这些途径促进脂肪氧化，防止TG积累和增强TG分解（脂解）。这包括SREBP-1c，PPAR-δ及其下游靶标的基因组调控，以及通过E2处理快速激活肌肉AMP激活的蛋白激酶（AMPK）。使用人类分化的前脂肪细胞进行的体外研究证实了我在体内关于SREBP-1c表达的发现，证明了E2对这种脂肪生成途径的调节。最后，我证明了ER在脂肪形成和维持人类脂肪细胞处于分化状态中的重要作用。结论。我的研究结果大大增强了我们对E2在肥胖和代谢中作用的认识。我发现了多种机制，通过这些机制，E2可以减少肥胖，并可能改善代谢健康。我的发现的结果具有多种含义，特别涉及更年期，激素替代疗法，改变性激素水平的内分泌失调以及基于性别的药物的潜力。

著录项

  • 作者

    D'Eon, Tara Michelle.;

  • 作者单位

    Tufts University.;

  • 授予单位 Tufts University.;
  • 学科 Chemistry Biochemistry.; Health Sciences Nutrition.
  • 学位 Ph.D.
  • 年度 2006
  • 页码 76 p.
  • 总页数 76
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 生物化学;预防医学、卫生学;
  • 关键词

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