Leptin signaling and leptin resistance.
Leptin signaling and leptin resistance.
复制标题
瘦素信号传导和瘦素抵抗
DOI：
10.1515/mr-2022-0017
复制
发表时间：
2022-08
期刊：
影响因子：
--
通讯作者：
Zheng, Ruimao
中科院分区：
文献类型：
--
作者：
Liu, Jiarui;Lai, Futing;Hou, Yujia;Zheng, Ruimao
随着肥胖和相关合并症的流行，旨在揭示调节能量稳态的机制的研究越来越受到关注。1994年，瘦素的克隆是代谢研究的一个里程碑。瘦素作为一种脂肪细胞因子，通过脑内的瘦素受体（LepR）调节食物摄入和能量平衡。瘦素水平的增加不能抑制进食和提高能量消耗被称为瘦素抵抗，其包括复杂的病理生理过程。在脑内，LepR表达神经元分布在下丘脑和其他脑区域，并且每个LepR表达神经元群体可以介导瘦素效应的特定方面。在表达LepR的神经元中，LepR与LepR的结合启动多个信号级联，包括Janus激酶（JAK）-信号转导和转录激活因子（STAT）、磷脂酰肌醇3-激酶（PI 3 K）-蛋白激酶B（AKT）、细胞外调节蛋白激酶（ERK）和AMP活化蛋白激酶（AMPK）信号传导等，介导瘦素的作用。这些发现将瘦素置于代谢和神经内分泌调节的交叉点，并使瘦素成为治疗肥胖和相关合并症的关键靶点。这篇综述强调了瘦素领域的主要发现，以更好地了解代谢稳态的机制，并指导安全有效的干预措施的发展，以治疗肥胖和相关疾病。
With the prevalence of obesity and associated comorbidities, studies aimed at revealing mechanisms that regulate energy homeostasis have gained increasing interest. In 1994, the cloning of leptin was a milestone in metabolic research. As an adipocytokine, leptin governs food intake and energy homeostasis through leptin receptors (LepR) in the brain. The failure of increased leptin levels to suppress feeding and elevate energy expenditure is referred to as leptin resistance, which encompasses complex pathophysiological processes. Within the brain, LepR-expressing neurons are distributed in hypothalamus and other brain areas, and each population of the LepR-expressing neurons may mediate particular aspects of leptin effects. In LepR-expressing neurons, the binding of leptin to LepR initiates multiple signaling cascades including janus kinase (JAK)–signal transducers and activators of transcription (STAT) phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT), extracellular regulated protein kinase (ERK), and AMP-activated protein kinase (AMPK) signaling, etc., mediating leptin actions. These findings place leptin at the intersection of metabolic and neuroendocrine regulations, and render leptin a key target for treating obesity and associated comorbidities. This review highlights the main discoveries that shaped the field of leptin for better understanding of the mechanism governing metabolic homeostasis, and guides the development of safe and effective interventions to treat obesity and associated diseases.