STAT3 phosphorylation in central leptin resistance.
STAT3 phosphorylation in central leptin resistance.
复制标题
中枢瘦素抵抗中的 STAT3 磷酸化
DOI：
10.1186/s12986-021-00569-w
复制
发表时间：
2021-04-13
影响因子：
4.5
通讯作者：
Yang G
中科院分区：
文献类型：
--
作者：
Liu H;Du T;Li C;Yang G
肥胖相关的代谢紊乱在全球范围内普遍存在，迫切需要能量稳态机制的探索。尽管众所周知，瘦素通过抑制食物摄入和促进能量消耗而在调节能量平衡中起核心作用，但大多数肥胖个体中瘦素抵抗的存在阻碍了瘦素治疗对这些疾病的利用。然而，瘦素抵抗的机制在很大程度上是未知的，尽管全球巨大的努力。目前解释瘦素抵抗的理论包括瘦素转运障碍、瘦素信号转导减弱、慢性炎症、内质网应激、自噬缺陷以及瘦素本身。瘦素激活的瘦素受体（leptin activated leptin receptor，LepRb）在下丘脑中通过多种途径传递信号，其中JAK 2-STAT 3途径是研究最多的一条途径，被认为是介导瘦素能量调节的主要途径。在瘦素刺激下，STAT 3的磷酸化是JAK 2-STAT 3通路中的关键事件之一，随后是该分子的二聚化和核转位。磷酸化的STAT 3（p-STAT 3）作为一种转录因子，与其靶基因POMC结合并调节其功能，发挥瘦素的生理功能。关于下丘脑中的POMC基因，然而关于其与STAT 3相互作用的细节知之甚少。p-STAT 3在DIO小鼠下丘脑中的表达及其意义有待进一步研究。本文综述了瘦素和瘦素抵抗的相关文献，并重点讨论了STAT 3磷酸化在中枢瘦素抵抗中的作用。
Mechanism exploitation of energy homeostasis is urgently required because of the worldwide prevailing of obesity-related metabolic disorders in human being. Although it is well known that leptin plays a central role in regulating energy balance by suppressing food intake and promoting energy expenditure, the existence of leptin resistance in majority of obese individuals hampers the utilization of leptin therapy against these disorders. However, the mechanism of leptin resistance is largely unknown in spite of the globally enormous endeavors. Current theories to interpret leptin resistance include the impairment of leptin transport, attenuation of leptin signaling, chronic inflammation, ER tress, deficiency of autophagy, as well as leptin itself. Leptin-activated leptin receptor (LepRb) signals in hypothalamus via several pathways, in which JAK2-STAT3 pathway, the most extensively investigated one, is considered to mediate the major action of leptin in energy regulation. Upon leptin stimulation the phosphorylation of STAT3 is one of the key events in JAK2-STAT3 pathway, followed by the dimerization and nuclear translocation of this molecule. Phosphorylated STAT3 (p-STAT3), as a transcription factor, binds to and regulates its target gene such as POMC gene, playing the physiological function of leptin. Regarding POMC gene in hypothalamus however little is known about the detail of its interaction with STAT3. Moreover the status of p-STAT3 and its significance in hypothalamus of DIO mice needs to be well elucidated. This review comprehends literatures on leptin and leptin resistance and especially discusses what STAT3 phosphorylation would contribute to central leptin resistance.
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DOI：
10.1152/ajpendo.00468.2002
发表时间：
2003-07-01
影响因子：
5.1
作者：
Banks, WA;Farrell, CL
通讯作者：
Farrell, CL
影响因子：
7.5
作者：
Aigner, Petra;Mizutani, Tatsuaki;Stoiber, Dagmar
通讯作者：
Stoiber, Dagmar
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
15.9
作者：
Bjornholm, Marie;Munzberg, Heike;Myers, Martin G., Jr.
通讯作者：
Myers, Martin G., Jr.
影响因子：
5.3
作者：
Cui, YX;Huang, L;Li, C
通讯作者：
Li, C