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Novel Human Hormone Sensitive Lipase (HSL) Null Mutation Provides Insight to the Mechanism of Dyslipidemia, Insulin Resistance, and PPARgamma Regulation.

机译:新型人类激素敏感性脂肪酶(HSL)空突变为血脂异常,胰岛素抵抗和PPARγ调节机制提供了见识。

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摘要

Type 2 diabetes (T2D) is a complex disease that represents a major global public health threat. A key risk factor in the development of T2D is impairment in lipolysis. Lipolysis is a metabolic pathway that regulates energy homeostasis through degradation of intracellular triacylglyceride (TAG) and release of fatty acids for use as energy substrates or lipid mediators in cellular processes. We report identification of a novel 19-base pair deletion in the human LIPE gene, which encodes hormone sensitive lipase (HSL), a key lipolytic enzyme for diacylglyceride (DAG) hydrolysis. This deletion results in absence of HSL protein and is associated with dyslipidemia and T2D. Absence at the level of the adipose tissue of HSL results in major impairment of lipolysis and alteration in expression of downstream target genes of nuclear receptors like peroxisome proliferator-activated receptor-gamma (PPARgamma). Characterization of the first human HSL knockout revealed a novel role for HSL in the regulation of adipose tissue adipogenesis and function, and highlights the serious metabolic consequences of a lipid storage defect.
机译:2型糖尿病(T2D)是一种复杂的疾病,代表着全球主要的公共卫生威胁。 T2D发生的关键风险因素是脂解障碍。脂解是一种代谢途径,通过降解细胞内三酰甘油酯(TAG)和释放脂肪酸来调节能量稳态,以用作细胞过程中的能量底物或脂质介体。我们报告鉴定在人类LIPE基因中的一种新型的19个碱基对的缺失,该基因编码荷尔蒙敏感性脂肪酶(HSL),甘油二酯(DAG)水解的关键脂解酶。这种缺失导致不存在HSL蛋白,并与血脂异常和T2D有关。 HSL脂肪组织水平的缺乏会导致脂解作用的严重损害以及核受体(如过氧化物酶体增殖物激活的受体-γ(PPARgamma))下游靶基因表达的改变。第一个人类HSL基因敲除的特征揭示了HSL在调节脂肪组织脂肪生成和功能中的新作用,并突出了脂质储存缺陷的严重代谢后果。

著录项

  • 作者

    Albert, Jessica.;

  • 作者单位

    University of Maryland, Baltimore.;

  • 授予单位 University of Maryland, Baltimore.;
  • 学科 Genetics.
  • 学位 Ph.D.
  • 年度 2012
  • 页码 151 p.
  • 总页数 151
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 地球物理学;
  • 关键词

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