Univ Lille Nord de France, INSERM UMR1011, UDSL, Institut Pasteur de Lille, Lille, France.
J Steroid Biochem Mol Biol. 2012 Jul;130(3-5):126-37. doi: 10.1016/j.jsbmb.2011.10.002. Epub 2011 Oct 17.
Today, we are witnessing a rising incidence of obesity worldwide. This increase is due to a sedentary life style, an increased caloric intake and a decrease in physical activity. Obesity contributes to the appearance of type 2 diabetes, dyslipidemia and cardiovascular complications due to atherosclerosis, and nephropathy. Therefore, the development of new therapeutic strategies may become a necessity. Given the metabolism controlling properties of nuclear receptors in peripheral organs (such as liver, adipose tissues, pancreas) and their implication in various processes underlying metabolic diseases, they constitute interesting therapeutic targets for obesity, dyslipidemia, cardiovascular disease and type 2 diabetes. The recent identification of the central nervous system as a player in the control of peripheral metabolism opens new avenues to our understanding of the pathophysiology of obesity and type 2 diabetes and potential novel ways to treat these diseases. While the metabolic functions of nuclear receptors in peripheral organs have been extensively investigated, little is known about their functions in the brain, in particular with respect to brain control of energy homeostasis. This review provides an overview of the relationships between nuclear receptors in the brain, mainly at the hypothalamic level, and the central regulation of energy homeostasis. In this context, we will particularly focus on the role of PPARα, PPARγ, LXR and Rev-erbα.
如今，我们见证了全球肥胖症发病率的上升。这种增长归因于久坐不动的生活方式、卡路里摄入量的增加和体力活动的减少。肥胖会导致 2 型糖尿病、血脂异常和动脉粥样硬化引起的心血管并发症以及肾病的出现。因此，开发新的治疗策略可能成为必要。鉴于核受体在周围器官（如肝脏、脂肪组织、胰腺）中的代谢控制特性及其在代谢疾病相关的各种过程中的作用，它们是肥胖症、血脂异常、心血管疾病和 2 型糖尿病的有趣治疗靶点。最近发现中枢神经系统在控制外周代谢中发挥作用，这为我们理解肥胖症和 2 型糖尿病的病理生理学以及治疗这些疾病的潜在新方法开辟了新的途径。虽然核受体在周围器官中的代谢功能已得到广泛研究，但对于它们在大脑中的功能，特别是在大脑对能量平衡的控制方面，我们知之甚少。本综述概述了大脑中的核受体（主要在下丘脑水平）与能量平衡的中枢调节之间的关系。在这种情况下，我们将特别关注 PPARα、PPARγ、LXR 和 Rev-erbα 的作用。
