NR1 nuclear hormone receptors, and skeletal muscle metabolism: insights into dyslipidemia and metabolic disease.

NR1 核激素受体和骨骼肌代谢：血脂异常和代谢疾病的见解。

• 批准号: nhmrc : 401573
• 负责人: Prof George Muscat
• 金额: $ 38.84万
• 依托单位: The University of Queensland
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2007
• 资助国家: 澳大利亚
• 起止时间: 2007-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/nr1-nuclear-hormone-metabolic-disease/78350
• 关键词: NR1; nuclear; hormone; receptors; skeletal

The significance of Nuclear hormone receptors (NRs) in disease is underscored by the range of pharmacopoeia for the treatment of NR-associated disorders (e.g 16% of the top 100 drugs target NRs). Orphan NR1 receptors are abundantly expressed in skeletal muscle, a major mass peripheral tissue that accounts for ~40% of total body weight, and energy expenditure. Muscle is the major site of glucose metabolism and, fatty acid oxidation. Furthermore, it is an important regulator of cholesterol homeostasis and HDL levels. Consequently, it has a significant role in insulin sensitivity, the blood lipid profile, lipid metabolism and obesity. Understanding the functional role of the orphan NR1 receptors in skeletal muscle in the context of inflammation, lipid and energy homeostasis is of paramount importance in further understanding the mechanistic basis of dyslipidemia, chronic inflammation, insulin sensitivity, diabetes and obesity. Identification of novel NR1 targets that regulate metabolism in a major mass peripheral tissue, and positively influence the risk factors for cardiovascular disease, provides platforms for potential therapeutic intervention. Cardiovascular disease is the foremost cause of global mortality, and was responsible for >15 million deaths in 2003.

核激素受体（NR）在疾病中的重要性通过用于治疗NR相关病症的药典范围来强调（例如，前100种药物中的16%靶向NR）。孤儿NR1受体在骨骼肌和能量消耗中大量表达，骨骼肌是占总体重约40%的主要外周组织。肌肉是葡萄糖代谢和脂肪酸氧化的主要场所。此外，它是胆固醇稳态和HDL水平的重要调节剂。因此，它在胰岛素敏感性、血脂谱、脂质代谢和肥胖中具有重要作用。了解骨骼肌中孤儿NR1受体在炎症、脂质和能量稳态背景下的功能作用对于进一步了解血脂异常、慢性炎症、胰岛素敏感性、糖尿病和肥胖的机制基础至关重要。新的NR1靶点的鉴定，调节代谢的主要质量外周组织，并积极影响心血管疾病的危险因素，提供了潜在的治疗干预的平台。心血管疾病是全球死亡的首要原因，2003年造成1 500万人死亡。