ERRgamma and skeletal muscle: insights into lipid utilization and catabolism

核激素受体（Nuclear hormone receptor, NRs）在疾病中的重要性被药典中用于治疗核激素受体相关疾病的范围所强调（例如，前100种药物中有16%靶向核激素受体）。ERRgamma受体在骨骼肌和能量消耗中大量表达，骨骼肌是一种主要的外周组织，约占体重的40%。肌肉是葡萄糖代谢和脂肪酸氧化的主要部位。因此，它在胰岛素敏感性、血脂谱、脂质代谢和肥胖中起着重要作用。了解骨骼肌孤儿ERR受体在炎症、脂质和能量稳态中的功能作用，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ERRgamma靶点的发现可以调节外周组织的代谢，并对心血管疾病的危险因素产生积极影响，为潜在的治疗干预提供了平台。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。

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). ERRgamma receptors are abundantly expressed in skeletal muscle, a major mass periperal tissue that acconts for ~40% of total body weight, and energy expenditure. Muscle is the major site of glucose metabolism and, fatty acid oxidation. Consequently, it has a significant role in insulin sensitivity, the blood lipid profile, lipid metabolism and obesity. Understanding the functional role of the orphan ERR 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 ERRgamma 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.