Institute for Diabetes and Cancer, Helmholtz Center Munich, Neuherberg, Germany.
Joint Heidelberg-IDC Translational Diabetes Program, Inner Medicine 1, Heidelberg University Hospital, Heidelberg, Germany.
Adv Exp Med Biol. 2022;1390:61-82. doi: 10.1007/978-3-031-11836-4_4.
Nuclear receptors are master regulators of energy metabolism through the conversion of extracellular signals into gene expression signatures. The function of the respective nuclear receptor is tissue specific, signal and co-factor dependent. While normal nuclear receptor function is central to metabolic physiology, aberrant nuclear receptor signaling is linked to various metabolic diseases such as type 2 diabetes mellitus, obesity, or hepatic steatosis. Thus, the tissue specific manipulation of nuclear receptors is a major field in biomedical research and represents a treatment approach for metabolic syndrome. This chapter focuses on key nuclear receptors involved in regulating the metabolic function of liver, adipose tissue, skeletal muscle, and pancreatic β-cells. It also addresses the importance of nuclear co-factors for fine-tuning of nuclear receptor function. The mode of action, role in energy metabolism, and therapeutic potential of prominent nuclear receptors is outlined.
核受体是通过将细胞外信号转化为基因表达特征来调节能量代谢的主调控因子。各核受体的功能具有组织特异性,依赖于信号和辅助因子。虽然正常的核受体功能对于代谢生理学至关重要,但异常的核受体信号与各种代谢疾病有关,如 2 型糖尿病、肥胖或肝脂肪变性。因此,核受体的组织特异性操作是生物医学研究的一个主要领域,也是代谢综合征的一种治疗方法。本章重点介绍参与调节肝脏、脂肪组织、骨骼肌和胰腺β细胞代谢功能的关键核受体。它还讨论了核辅助因子对于核受体功能精细调节的重要性。概述了主要核受体的作用机制、在能量代谢中的作用以及治疗潜力。