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leptin signaling and leptin resistance

Frontiers of Medicine 2013年第2期7卷 207-222页

作者： Yingjiang Zhou Liangyou Rui Cambridge Laboratories Pfizer Worldwide Research&DevelopmentCambridgeMA 02139USA Department of Molecular and Integrative Physiology University of Michigan Medical SchoolAnn ArborMI 48109USA

leptin is secreted into the bloodstream by adipocytes and is required for the maintenance of energy homeostasis and body weight.leptin deficiency or genetic defects in the components of the leptin signaling pathways cause obesity.leptin controls energy balance and body weight mainly through leptin receptor b(LEPRb)-expressing neurons in the brain,particularly in the hypothalamus.These LEPRb-expressing neurons function as the first-order neurons that project to the second-order neurons located within and outside the hypothalamus,forming a neural network that controls the energy homeostasis and body weight.Multiple factors,including inflammation and endoplasmic reticulum(ER)stress,contribute to leptin resistance.leptin resistance is the key risk factor for obesity.This review is focused on recent advance about leptin action,leptin signaling,and leptin resistance.

关键词： leptin signaling leptin receptor energy balance leptin resistance obesity

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leptin in normal physiology and leptin resistance

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Science Bulletin 2016年第19期61卷 1480-1488,1469页

作者：李淑芬李希 Key Laboratory of Metabolic Molecular Medicine The Ministry of Education Department of Biochemistry and Molecular Biology Fudan University Shanghai Medical College

自从1994年瘦素作为一个脂肪细胞因子被发现,关于瘦素的研究已经取得了很多进展.瘦素与瘦素受体的结合,在中枢神经系统,特别是在下丘脑中激活STAT3依赖和非依赖的信号通路、在维持能量稳态、神经内分泌作用和代谢等方面都发挥了很重要... 详细信息

自从1994年瘦素作为一个脂肪细胞因子被发现,关于瘦素的研究已经取得了很多进展.瘦素与瘦素受体的结合,在中枢神经系统,特别是在下丘脑中激活STAT3依赖和非依赖的信号通路、在维持能量稳态、神经内分泌作用和代谢等方面都发挥了很重要的作用.瘦素抵抗是肥胖的一个重要危险因素.目前提出的引起瘦素抵抗的机制主要包括瘦素运输受损、瘦素信号通路削弱、内质网应激、炎症和自噬缺陷.在此,我们对瘦素的功能、瘦素的信号通路,以及瘦素抵抗等进行了综述,希望可以为对抗肥胖的研究提供新的思路.

关键词： leptin biology leptin function leptin signaling leptin resistance Energy homeostasis

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Role of leptin in Immunity

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Cellular & Molecular Immunology 2007年第1期4卷 1-13页

作者： Queenie Lai Kwan Lam Department of Pathology and Center of Infection and Immunology The University of Hong Kong

leptin, a protein hormone produced by the adipocytes, has long been recognized to regulate metabolism, neuroendorine and other physiological functions. Early findings of increased leptin production during infection and inflammation and dysregulated immune response in leptin signaling-deficient mice provide strong evidence for the involvement of leptin in the immune responses. Recent data have established the regulatory function for leptin in immunity similar to the function of a pro-inflammatory cytokine, while gene-targeting studies also demonstrated an essential role of leptin in regulating hematopoiesis and lymphopoiesis. Moreover, there has been increasing evidence that leptin is involved in the pathogenesis of various autoimmune diseases. This review discusses recent advances in understanding the role of leptin in immunity and leptin-signaling pathways involved in modulating immune homeostasis and autoimmune pathogenesis. Cellular ＆ Molecular Immunology. 2007;4（1）：1-13.

关键词： leptin leptin signaling pro-inflammatory cytokine immune response autoimmune disease

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Structural plasticity of human leptin binding to its receptor LepR

hLife

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hLife 2023年第2期1卷 115-123页

作者： Yufeng Xie Xiaoxiong Li Jianxun Qi Guijun Shang Defen Lu George Fu Gao CAS Key Laboratory of Pathogen Microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijingChina Department of Basic Medical Sciences School of MedicineTsinghua UniversityBeijingChina Shanxi Academy of Advanced Research and Innovation ShanxiChina Shanxi Provincial Key Laboratory for Major Infectious Disease Response ShanxiChina College of Life Sciences Shanxi Agricultural UniversityShanxiChina

leptin receptor(LepR)signaling plays an essential role in balancing food intake and energy expenditure.The architec-ture of LepR signaling assembly is critical for its function.In this study,we determined the structures of three distinct conformations of human leptin–LepR using cryo-electron microscopy at resolutions of 3.88,3.77,and 3.58Å.Both 2:2 and 3:3 stoichiometric assemblies were observed,and the complexes exhibited asymmetric open conformations.Lep-tin undergoes substantial rearrangement of its flexible regions to accommodate binding to LepR.The assembled leptin–LepR complexes connect through a“hand-in-hand”geometry.The open,interlocked 3:3 trimeric assembly results from the engagement of a third leptin–LepR heterodimer with a 2:2 dimer.The asymmetric geometry of LepR is substantially distinct from that of other gp130 cytokine homologs,and that may be due to the twisted and rigid interface between the D3 and D4 domains.These results highlight the distinct engagement of leptin with LepR and provide important insights into the structural plasticity of LepR-signaling assemblies.

关键词： LepR leptin signaling cryo-electron microscopy(cryo-EM)

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