Metabolic factors in the regulation of hypothalamic innate immune responses in obesity.
Metabolic factors in the regulation of hypothalamic innate immune responses in obesity.
复制标题
肥胖患者下丘脑天然免疫反应调节中的代谢因素。
DOI：
10.1038/s12276-021-00666-z
复制
发表时间：
2022-04
影响因子：
12.8
通讯作者：
Koliwad, Suneil K.
中科院分区：
文献类型：
--
作者：
Folick, Andrew;Cheang, Rachel T.;Valdearcos, Martin;Koliwad, Suneil K.
下丘脑是体重和能量稳态的中枢调节器。越来越多的证据表明，下丘脑内侧基底核（MBH）的先天性免疫激活是饮食诱导的肥胖症发病机制中的关键因素。小胶质细胞是脑实质中的常驻免疫细胞，已被证明在脑功能的多个方面发挥作用，包括电路细化和突触修剪。因此，小胶质细胞也与神经系统疾病的发展和进展有关。小胶质细胞表达多种营养、激素和免疫信号的受体，并对这些信号作出反应，这些信号调节它们在不同脑区的不同功能。我们发现MBH内的小胶质细胞对高脂饮食有感觉和反应，并调节下丘脑神经元的功能，以促进食物摄入和肥胖。MBH内的神经元、神经胶质细胞和免疫细胞被定位为感知和响应循环信号，这些信号调节它们协调全身能量代谢方面的能力。在这里，我们回顾了目前的知识，这些外周信号如何调节先天性免疫反应的MBH，使小胶质细胞调节代谢控制。大脑中导致代谢功能障碍的免疫细胞可以为治疗肥胖提供一个治疗靶点。在一篇综述文章中，来自美国加州大学弗朗西斯科分校的Martin Valdearcos和Suneil Koliwad领导的研究小组讨论了将大脑下丘脑区域中发现的小胶质细胞和其他免疫细胞与食物摄入和体重增加的调节联系起来的证据。研究人员描述了激素、炎症分子、营养物质和微生物组衍生因子如何影响小胶质细胞，从而影响免疫细胞如何与负责代谢控制的神经元相互作用。尽管关于小胶质细胞功能的哪些方面与肥胖促进是不可或缺的，仍有很多东西有待了解，但作者认为，原则上，靶向这些免疫细胞的药物可以帮助对抗过度体重增加和相关的代谢紊乱。
The hypothalamus is a central regulator of body weight and energy homeostasis. There is increasing evidence that innate immune activation in the mediobasal hypothalamus (MBH) is a key element in the pathogenesis of diet-induced obesity. Microglia, the resident immune cells in the brain parenchyma, have been shown to play roles in diverse aspects of brain function, including circuit refinement and synaptic pruning. As such, microglia have also been implicated in the development and progression of neurological diseases. Microglia express receptors for and are responsive to a wide variety of nutritional, hormonal, and immunological signals that modulate their distinct functions across different brain regions. We showed that microglia within the MBH sense and respond to a high-fat diet and regulate the function of hypothalamic neurons to promote food intake and obesity. Neurons, glia, and immune cells within the MBH are positioned to sense and respond to circulating signals that regulate their capacity to coordinate aspects of systemic energy metabolism. Here, we review the current knowledge of how these peripheral signals modulate the innate immune response in the MBH and enable microglia to regulate metabolic control. Immune cells in the brain that contribute to metabolic dysfunction could offer a therapeutic target for treating obesity. In a review article, a team led by Martin Valdearcos and Suneil Koliwad from the University of California, San Francisco, USA, discuss the evidence linking microglia and other immune cells found in the brain’s hypothalamus region to the regulation of food intake and weight gain. The researchers describe how hormones, inflammatory molecules, nutrients, and microbiome-derived factors can all impact microglia in ways that affect how the immune cells interact with the neurons responsible for metabolic control. Although much remains to be learned about which aspects of microglial function are integral to obesity promotion, the authors argue that, in principle, drugs that target these immune cells could help combat excess weight gain and related metabolic disorders.
登录
查看更多内容
影响因子：
7.7
作者：
Cani, Patrice D.;Amar, Jacques;Burcelin, Remy
通讯作者：
Burcelin, Remy
下丘脑胰高血糖素样肽1受体足够，但对于调节小鼠的能量平衡和葡萄糖稳态不需要。
影响因子：
7.7
作者：
Burmeister MA;Ayala JE;Smouse H;Landivar-Rocha A;Brown JD;Drucker DJ;Stoffers DA;Sandoval DA;Seeley RJ;Ayala JE
通讯作者：
Ayala JE
影响因子：
--
作者：
Corella, Dolores;Peloso, Gina;Arnett, Donna K.;Demissie, Serkalem;Cupples, L. Adrienne;Tucker, Katherine;Lai, Chao-Qiang;Parnell, Laurence D.;Coltell, Oscar;Lee, Yu-Chi;Ordovas, Jose M.
通讯作者：
Ordovas, Jose M.
影响因子：
12.7
作者：
Baufeld C;Osterloh A;Prokop S;Miller KR;Heppner FL
通讯作者：
Heppner FL
影响因子：
7.7
作者：
Beutler, Lisa R.;Corpuz, Timothy, V;Knight, Zachary A.
通讯作者：
Knight, Zachary A.