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leptin signaling and leptin resistance

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Medical Review 2022年第4期2卷 363-384页

作者： Jiarui Liu Futing Lai Yujia Hou Ruimao Zheng Department of Anatomy Histology and EmbryologySchool of Basic Medical SciencesHealth Science CenterPeking UniversityBeijing 100191China Neuroscience Research Institute Peking UniversityBeijing 100191China Key Laboratory for Neuroscience of Ministry of Education Peking UniversityBeijing 100191China Key Laboratory for Neuroscience of National Health Commission Peking UniversityNO.38 Xueyuan RoadBeijing 100191China

With the prevalence of obesity and associated comorbidities,studies aimed at revealing mechanisms that regulate energy homeostasis have gained increasing *** 1994,the cloning of leptin was a milestone in metabolic *** an adipocytokine,leptin governs food intake and energy homeostasis through leptin receptors(LepR)in the *** failure of increased leptin levels to suppress feeding and elevate energy expenditure is referred to as leptin resistance,which encompasses complex pathophysiological *** 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 *** 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 *** findings place leptin at the intersection of metabolic and neuroendocrine regulations,and render leptin a key target for treating obesity and associated *** 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.

关键词： leptin leptin cellular pathways leptin neural pathways leptin resistance

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

Since the discovery of leptin as an adipokine in1994, much progress has been made in the research about leptin. Circulating leptin binds to leptin receptor, activates STAT3-dependent and STAT3-independent signaling pathways, and plays an effective role in energy homeostasis, neuroendocrine function and metabolism mainly through acting on the central nervous system, especially the hypothalamus. leptin resistance is considered as a key risk factor for obesity. Various mechanisms have been formulated in order to explain leptin resistance, including impairment in leptin transport, attenuation in leptin signaling, ER stress, inflammation and deficiency in autophagy. Here, we review our current knowledge about leptin action, leptin signaling and leptin resistance, hoping to provide new ideas for the battle against obesity.

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

Cellular and Molecular Basis of leptin resistance in Obese Patients

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Food Therapy and Health Care 2020年第3期2卷 122-128页

作者： Xiao-ting Ma Shao-qin Ge Hebei University Baoding 071002China

Obesity is a major risk factor for diabetes,cardiovascular disease,and certain *** arises from a chronic positive energy *** is usually due to unrestricted access to food in the context of genetic and epigenetic *** an increasingly sedentary *** the past few decades,our understanding of the fluid and nervous systems that mediate energy balance control has greatly ***,our ability to formulate effective strategies to slow the current obesity epidemic has been hampered,mainly because we have limited knowledge of the resistance mechanisms of metabolic hormones such as *** to leptin is a sign of obesity,leptin is a key hormone for neuroendocrine control of energy *** the past few years,we have made tremendous progress in our in-depth research on the cellular pathways that disrupt the action of *** this review,we discuss the molecular mechanisms of leptin resistance and how to use them as targets for obesity drug therapy.

关键词： Obesity leptin leptin resistance Cellular basis Molecular basis

The Mechanism of Regulating leptin resistance in Obesity and the Influence of Adjusting Methylation of OB-R,POMC Gene Promoter of Wendan Decoction (温胆汤)

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World Journal of Integrated Traditional and Western Medicine 2020年第6期6卷 23-30页

作者： YANG Hai-yan YU Song-ren WANG Ping SHU Qing CHENG Shao-min Science and Technology College Jiangxi University of traditional Chinese MedicineNanchang 330000China College of Traditional Chinese Medicine Jiangxi University of traditional Chinese MedicineNanchang 330000China Graduate student of Jiangxi University of traditional Chinese Medicine Nanchang 330000China

Objective:To explore the mechanism of Wendan Decoction(温胆汤)regulating leptin resistance in obesity by analyzing the level of leptin in peripheral blood,the expression of leptin receptor and signal pathway molecule POMC in *** analyze the methylation status of the gene promoters of leptin receptor and POMC in obese rats fed with high fat diet,and the influence of adjusting methylation of OB-R,POMC gene promoter about Wendan ***:Model rats were randomly divided into model control group and drug observation group,additional normal rats with 8 rats in each *** models were established by high fat *** observation group was treated with Wendan Decoction(温胆汤)and the other two groups were treated with sterilized drinking water once a day for 6 *** weight was recorded every week during the *** blood and hypothalamus were collected at the end of the *** serum leptin level was measured by ELISA method,and the expression of OB-R and POMC in hypothalamus was detected by RT-qPCR *** level of OB-R and POMC promoter detected by methylation specific ***:Our results revealed that Wendan Decoction(温胆汤)could effectively reduce body weight,the body weight in the drug observation group was significantly lower than that in the model control group,and the difference between the two groups was statistically *** level of leptin in peripheral blood and the expression of OB-R in hypothalamus were consistent with the trend of body *** heavier the weight,the higher the level of leptin and *** Decoction(温胆汤)could reduce the level of leptin and OB-R in peripheral blood while reducing body *** with the model control group,the difference was statistically *** heavier the weight,the lower the level of POMC *** Decoction(温胆汤)could increase the expression of POMC while reducing body weight,which had statistical significance compared with the m

关键词： Wendan Decoction(温胆汤) Proopiomelanocortin Obesity leptin resistance Methylation

Influence of catgut implantation at acupoints on leptin and insulin resistance in simple obesity rats

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Journal of Traditional Chinese Medicine 2012年第3期32卷 477-481页

作者： Runhu Yan Xiaoming Liu Jie Bai Jiang Yu Jinsong Gu College of Cosmetology Medicine of DalianMedical University Research institute of Integrated Tradi-tional and Western Medicine of Dalian Medical University Dalian 116044 China Dermatology of The First Affiliated Hospitalof Dalian Medical University Dalian 116011 China Jiang Yu Jinsong Gu College of Cosmetology Medicine of Dalian Medical University Dalian 116044 China

OBJECTIVES:To investigate the influence of catgut implantation at acupoints on leptin resistance(LR) and insulin resistance(IR) in the simple obesity ***:Rats were made obese with high-fat diets,after which surgical catgut was implanted at Zusanli(ST 36) and Neiting(ST 44) acupoints once a week for 4 weeks(implantation group).Rats from the implantation group were compared with normal rats and unoperated obese rats(control group).Gene expression of the leptin receptor(OB-R) was evaluated using RT-PCR and northern *** and hypothalamus leptin and insulin(INS) levels were determined by *** weight,Lee's index,body fat,serum and hypothalamus leptin and INS levels,and hypothalamic OB-R gene expression were determined before and after ***:Body weights,Lee's index,body fat,and serum leptin and INS levels were significantly higher in obese than in normal *** leptin and INS levels and OB-R gene expression were significantly lower in obese *** implantation at acupoint promoted weight loss and decreased serum leptin and INS *** leptin and INS levels and OB-R gene expression increased ***:Catgut implantation at acupoint adjusts central and peripheral leptin and promotes hypothalamic OB-R gene *** may be an important method for regulation of LR,IR and abnormal endocrinology and metabolism.

关键词： Thread-embedding acupoint ligation Obesity leptin resistance Insulin resistance Receptors,leptin Blood-cerebral barrier

Obesity:an evolutionary context

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Life Metabolism 2022年第1期1卷 10-24页

作者： John R.Speakman Joel K.Elmquist Shenzhen Key Laboratory of Metabolic Health Center for Energy Metabolism and ReproductionShenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhenChina School of Biological Sciences University of AberdeenAberdeenUK State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental biologyChinese Academy of SciencesBeijingChina CAS Center of Excellence in Animal Evolution and Genetics KunmingChina Departments of Internal Medicine and Pharmacology Center for Hypothalamic ResearchUniversity of Texas SouthwesternDallasTXUSA

People completely lacking body fat(lipodystrophy/lipoatrophy)and those with severe obesity both show profound metabolic and other health *** levels of body fat somewhere between these limits would,therefore,appear to be *** different models might be *** traditional is a set point(SP)where the levels are regulated around a fixed ***,dual-intervention point(DIP)is a system that tolerates fairly wide variation but is activated when critically high or low levels are *** DIP system seems to fit our experience much better than an SP,and models suggest that it is more likely to have evolved.A DIP system may have evolved because of two contrasting selection *** the lower end,we may have been selected to avoid low levels of fat as a buffer against starvation,to avoid disease-induced anorexia,and to support *** the upper end,we may have been selected to avoid excess storage because of the elevated risks of *** upper limit of control seems to have malfunctioned because some of us deposit large fat stores,with important negative health *** has evolution not protected us against this problem?One possibility is that the protective system slowly fell apart due to random mutations after we dramatically reduced the risk of being predated during our evolutionary *** chance,it fell apart more in some people than others,and these people are now unable to effectively manage their weight in the face of the modern food *** understand the evolutionary context of obesity,it is important to separate the adaptive reason for storing some fat(*** lower intervention point),from the nonadaptive reason for storing lots of fat(a broken upper intervention point).The DIP model has several consequences,showing how we understand the obesity problem and what happens when we attempt to treat it.

关键词： obesity BMI body fat adiposity evolution selection adaptive leptin resistance metabolic programming dual-intervention point model set-point model

An Overview of leptin and the Th1/Th2 Balance

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Open Journal of Immunology 2014年第2期4卷 42-50页

作者： Buenaventura Brito Diaz Itahisa Marcelino Rodriguez Delia Almeida Gonzalez María del Cristo Rodríguez Pérez Antonio Cabrera de León Research Unit University Hospital Nuestra Senora de Candelaria TenerifeSpain Immunology Unit University Hospital Nuestra Senora de Candelaria TenerifeSpain University of La Laguna TenerifeSpain

Adipocytes produce hormones and adipokines, among others leptin, with metabolic and inflammatory responses. The role of leptin involves different subsets of the immune system. Low levels of serum leptin concentrations are associated with bacterial infections and produce susceptibility to allergic diseases and type Th2 autoimmune diseases. High levels of leptin are associated with Th1 autoimmune diseases via inflammatory responses. leptin resistance, that happens in obesity, is characterized by the presence of high levels of serum leptin itself accompanied by a clinical situation of a Th2 response. There is a relationship between obesity, leptin resistance, altered immunity and sex hormones. Serum leptin concentration (Th1 response) in women is higher than in men maybe to achieve the balance Th1/Th2 because of the high level of estrogenic hormones (Th2 response) in women.

关键词： Obesity leptin resistance Autoimmunity Sex Hormones

Metabolic regulation by protein tyrosine phosphatases

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The Journal of Biomedical Research 2014年第3期28卷 157-168页

作者： Hilla Knobler Ari Elson Diabetes and Metabolic Disease Unit Kaplan Medical Center Department of Molecular Genetics the Weizmann Institute of Science

Obesity and the metabolic syndrome and their associated morbidities are major public health issues, whose prevalence will continue to increase in the foreseeable future. Aberrant signaling by the receptors for leptin and insulin plays a pivotal role in development of the metabolic syndrome. More complete molecular-level understanding of how both of these key signaling pathways are regulated is essential for full characterization of obesity, the metabolic syndrome, and type lI diabetes, and for developing novel treatments for these diseases. Phosphorylation of proteins on tyrosine residues plays a key role in mediating the effects of leptin and insulin on their target cells. Here, we discuss the molecular methods by which protein tyrosine phosphatases, which are key physiological regulators of protein phosphorylation in vivo, affect signaling by the leptin and insulin receptors in their major target tissues.

关键词： obesity diabetes metabolic syndrome insulin resistance leptin resistance tyrosine phosphatase PTP