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The impact of endothelial cell death in the brain and its role after stroke: A systematic review 脑内皮细胞死亡的影响及其在脑卒中后的作用:一项系统综述
IF 6.4 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2019-09-25 DOI: 10.15698/cst2019.11.203
M. Zille, Maulana Ikhsan, Yun Jiang, J. Lampe, Jan Wenzel, M. Schwaninger
The supply of oxygen and nutrients to the brain is vital for its function and requires a complex vascular network that, when disturbed, results in profound neurological dysfunction. As part of the pathology in stroke, endothelial cells die. As endothelial cell death affects the surrounding cellular environment and is a potential target for the treatment and prevention of neurological disorders, we have systematically reviewed important aspects of endothelial cell death with a particular focus on stroke. After screening 2876 publications published between January 1, 2010 and August 7, 2019, we identified 154 records to be included. We found that endothelial cell death occurs rapidly as well as later after the onset of stroke conditions. Among the different cell death mechanisms, apoptosis was the most widely investigated (92 records), followed by autophagy (20 records), while other, more recently defined mechanisms received less attention, such as lysosome-dependent cell death (2 records) and necroptosis (2 records). We also discuss the differential vulnerability of brain cells to injury after stroke and the role of endothelial cell death in the no-reflow phenomenon with a special focus on the microvasculature. Further investigation of the different cell death mechanisms using novel tools and biomarkers will greatly enhance our understanding of endothelial cell death. For this task, at least two markers/criteria are desirable to determine cell death subroutines according to the recommendations of the Nomenclature Committee on Cell Death.
向大脑提供氧气和营养物质对其功能至关重要,需要一个复杂的血管网络,一旦受到干扰,就会导致严重的神经功能障碍。作为中风病理的一部分,内皮细胞死亡。由于内皮细胞死亡影响周围细胞环境,是治疗和预防神经系统疾病的潜在靶点,我们系统地回顾了内皮细胞死亡的重要方面,特别关注中风。在筛选了2010年1月1日至2019年8月7日期间发表的2876份出版物后,我们确定了154份记录。我们发现内皮细胞的死亡发生得很快,并且在中风发作后发生得更晚。在不同的细胞死亡机制中,细胞凋亡是研究最广泛的(92条记录),其次是自噬(20条记录),而其他最近定义的机制受到的关注较少,如溶酶体依赖性细胞死亡(2条记录)和坏死下垂(2条记录)。我们还讨论了脑卒中后脑细胞对损伤的不同脆弱性,以及内皮细胞死亡在无血流现象中的作用,特别关注微血管。使用新的工具和生物标志物进一步研究不同的细胞死亡机制将大大提高我们对内皮细胞死亡的理解。对于这项任务,根据细胞死亡命名委员会的建议,至少需要两个标记/标准来确定细胞死亡子程序。
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引用次数: 44
Acyl-CoA-binding protein (ACBP): the elusive 'hunger factor' linking autophagy to food intake. 酰基辅酶A结合蛋白(ACBP):将自噬与食物摄入联系起来的难以捉摸的“饥饿因子”
IF 4.1 Q2 CELL BIOLOGY Pub Date : 2019-09-24 DOI: 10.15698/cst2019.10.200
José Manuel Bravo-San Pedro, Valentina Sica, Frank Madeo, Guido Kroemer

The best-known appetite-regulating factors identified in rodents are leptin, an appetite inhibitor, and ghrelin, an appetite stimulator. Rare cases of loss-of-functions mutations affecting leptin and its receptor, as well as polymorphisms concerning ghrelin and its receptor, have been documented in human obesity, apparently validating the relevance of leptin and ghrelin for human physiology. Paradoxically, however, the overwhelming majority of obese individuals manifest high leptin and low ghrelin plasma levels, suggesting that both factors are not directly disease-relevant. We recently discovered that acyl-CoA-binding protein (ACBP), also known as diazepam-binding inhibitor (DBI), acts as an efficient lipogenic and appetite stimulator in mice. Indeed, in response to starvation, ACBP/DBI is released from tissues in an autophagy-dependent fashion and increases in the plasma. Intravenous injection of ACBP/DBI stimulates feeding behavior through a reduction of circulating glucose levels, and consequent activation of orexigenic neurons in the hypothalamus. In contrast, neutralization of ACBP/DBI abolishes the hyperphagia observed after starvation of mice. Of note, ACBP/DBI is increased in the plasma of obese persons and mice, pointing to a convergence (rather than divergence) between its role in appetite stimulation and human obesity. Based on our results, we postulate a novel 'hunger reflex' in which starvation induces a surge in extracellular ACBP/DBI, which in turn stimulates feeding behavior. Thus, ACBP/DBI might be the elusive 'hunger factor' that explains increased food uptake in obesity.

在啮齿类动物中发现的最著名的食欲调节因子是食欲抑制剂瘦素和食欲刺激因子胃饥饿素。在人类肥胖中,已经记录了影响瘦素及其受体的罕见功能缺失突变,以及与胃促生长素及其受体有关的多态性,这显然证实了瘦素和胃促生长素与人类生理学的相关性。然而,矛盾的是,绝大多数肥胖者表现出高瘦素和低胃饥饿素血浆水平,这表明这两个因素与疾病无关。我们最近发现酰基辅酶A结合蛋白(ACBP),也称为地西泮结合抑制剂(DBI),在小鼠中是一种有效的脂肪生成和食欲刺激因子。事实上,作为对饥饿的反应,ACBP/DBI以自噬依赖的方式从组织中释放,并在血浆中增加。静脉注射ACBP/DBI通过降低循环葡萄糖水平和随后激活下丘脑中的食欲神经元来刺激进食行为。相反,ACBP/DBI的中和消除了小鼠饥饿后观察到的高吞噬。值得注意的是,肥胖者和小鼠的血浆中ACBP/DBI增加,这表明其在食欲刺激中的作用与人类肥胖之间存在趋同(而非分歧)。基于我们的研究结果,我们假设了一种新的“饥饿反射”,即饥饿诱导细胞外ACBP/DBI激增,进而刺激进食行为。因此,ACBP/DBI可能是解释肥胖患者食物摄入增加的难以捉摸的“饥饿因素”。
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引用次数: 0
Inflammation induced PD-L1-specific T cells 炎症诱导的PD-L1特异性T细胞
IF 6.4 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2019-09-13 DOI: 10.15698/cst2019.10.201
Shamaila Munir, M. Lundsager, M. Jørgensen, M. Hansen, Trine H Petersen, C. Bonefeld, C. Friese, Ö. Met, P. Straten, M. Andersen
PD-L1-specific T cells are a natural part of the T-cell repertoire in humans. Hence, we have previously described spontaneous CD8+ and CD4+ T-cell reactivity against PD-L1 in the peripheral blood of patients with various cancers as well as in healthy donors. It is well described that the expression of the PD-L1 protein is introduced in cells by pro-inflammatory cytokines, e.g. IFN-γ. In the current study, we were able to directly link inflammation with PD-L1-specific T cells by showing that inflammatory mediators such as IFN-γ generate measurable numbers of PD-L1-specific T cells in human PBMCs as well as in in vivo models. These PD-L1-specific T cells can vigorously modulate the cell compartments of the local environment. PD-L1-specific T cells may be important for immune homeostasis by sustaining the ongoing inflammatory response by the suppression of regulatory cell function both directly and indirectly.
pd - l1特异性T细胞是人类T细胞库的自然组成部分。因此,我们之前已经描述了各种癌症患者和健康供者外周血中自发的CD8+和CD4+ t细胞对PD-L1的反应性。已经很好地描述了PD-L1蛋白的表达是通过促炎细胞因子(如IFN-γ)引入细胞的。在目前的研究中,我们能够直接将炎症与pd - l1特异性T细胞联系起来,通过显示炎症介质如IFN-γ在人pbmc和体内模型中产生可测量数量的pd - l1特异性T细胞。这些pd - l1特异性T细胞可以大力调节局部环境的细胞区室。pd - l1特异性T细胞可能通过直接或间接抑制调节细胞功能来维持持续的炎症反应,从而对免疫稳态起重要作用。
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引用次数: 13
Gold Nanoparticles sensitize pancreatic cancer cells to gemcitabine. 金纳米粒子使癌症胰腺细胞对吉西他滨敏感。
IF 6.4 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2019-07-31 DOI: 10.15698/cst2019.08.195
Yanyan Huai, Yushan Zhang, Xunhao Xiong, Shamik Das, Resham Bhattacharya, Priyabrata Mukherjee

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest solid cancers with dismal prognosis. Several mechanisms that are mainly responsible for aggressiveness and therapy resistance of PDAC cells include epithelial to mesenchymal transition (EMT), stemness and Mitogen Activated Protein Kinase (MAPK) signaling. Strategies that inhibit these mechanisms are critically important to improve therapeutic outcome in PDAC. In the current study, we wanted to investigate whether gold nanoparticles (AuNPs) could sensitize pancreatic cancer cells to the chemotherapeutic agent gemcitabine. We demonstrated that treatment with AuNPs of 20 nm diameter inhibited migration and colony forming ability of pancreatic cancer cells. Pre-treatment with AuNPs sensitized pancreatic cancer cells to gemcitabine in both viability and colony forming assays. Mechanistically, pre-treatment of pancreatic cancer cells with AuNPs decreased gemcitabine induced EMT, stemness and MAPK activation. Taken together, these findings suggest that AuNPs could be considered as a potential agent to sensitize pancreatic cancer cells to gemcitabine.

胰腺导管腺癌(PDAC)是最致命的实体癌之一,预后极差。主要导致PDAC细胞侵袭性和治疗耐药性的几种机制包括上皮-间充质转化(EMT)、干性和丝裂原活化蛋白激酶(MAPK)信号传导。抑制这些机制的策略对于改善PDAC的治疗效果至关重要。在目前的研究中,我们想研究金纳米颗粒(AuNP)是否可以使胰腺癌症细胞对化疗剂吉西他滨敏感。我们证明用直径为20nm的AuNPs处理抑制了胰腺癌症细胞的迁移和集落形成能力。在生存力和集落形成测定中,AuNP预处理使癌症胰腺细胞对吉西他滨敏感。从机制上讲,用AuNP预处理胰腺癌症细胞降低了吉西他滨诱导的EMT、干性和MAPK活化。总之,这些发现表明AuNPs可以被认为是一种潜在的使胰腺癌症细胞对吉西他滨敏感的药剂。
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引用次数: 0
Unraveling the molecular principles by which ceramides commit cells to death 揭示神经酰胺导致细胞死亡的分子原理
IF 6.4 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2019-07-16 DOI: 10.15698/cst2019.08.196
Shashank Dadsena, Dina G. Hassan, J. Holthuis
Ceramides are central intermediates of sphingolipid metabolism that can activate a variety of tumor suppressive cellular programs, including cell cycle arrest, senescence and apoptosis. Indeed, perturbations in ceramide generation and turnover are frequently linked to cancer cell survival and resistance to chemotherapy. Consequently, the potential of ceramide-based therapeutics in the treatment of cancer has become a major focus of interest. A growing body of evidence indicates that ceramides can act directly on mitochondria to trigger apoptotic cell death. However, molecular details of the underlying mechanism are scarce. In our recent study (Dadsena S et al., 2019, Nat Commun 10:1832), we used a photoactivatable ceramide probe combined with computer simulations and functional studies to identify the voltage-dependent anion channel VDAC2 as a critical effector of ceramide-induced mitochondrial apoptosis. Collectively, our findings provide a novel molecular framework for how ceramides execute their widely acclaimed anti-neoplastic activities.
神经酰胺是鞘脂代谢的中心中间体,可以激活多种肿瘤抑制细胞程序,包括细胞周期停滞、衰老和凋亡。事实上,神经酰胺生成和周转的扰动通常与癌症细胞的存活和化疗耐药性有关。因此,神经酰胺治疗癌症的潜力已成为人们关注的主要焦点。越来越多的证据表明,神经酰胺可以直接作用于线粒体,引发细胞凋亡。然而,关于潜在机制的分子细节却很少。在我们最近的研究中(Dadsena S et al.,2019,Nat Commun 10:1832),我们使用可光活化神经酰胺探针,结合计算机模拟和功能研究,确定电压依赖性阴离子通道VDAC2是神经酰胺诱导的线粒体凋亡的关键效应器。总之,我们的发现为神经酰胺如何发挥其广受好评的抗肿瘤活性提供了一个新的分子框架。
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引用次数: 12
Immunosurveillance of cancer cell stress. 癌症细胞应激的免疫监测
IF 4.1 Q2 CELL BIOLOGY Pub Date : 2019-07-03 DOI: 10.15698/cst2019.09.198
Seila Lorenzo-Herrero, Christian Sordo-Bahamonde, Segundo González, Alejandro López-Soto

Cancer development is tightly controlled by effector immune responses that recognize and eliminate malignantly transformed cells. Nonetheless, certain immune subsets, such as tumor-associated macrophages, have been described to promote tumor growth, unraveling a double-edge role of the immune system in cancer. Cell stress can modulate the crosstalk between immune cells and tumor cells, reshaping tumor immunogenicity and/or immune function and phenotype. Infiltrating immune cells are exposed to the challenging conditions typically present in the tumor microenvironment. In return, the myriad of signaling pathways activated in response to stress conditions may tip the balance toward stimulation of antitumor responses or immune-mediated tumor progression. Here, we explore how distinct situations of cellular stress influence innate and adaptive immunity and the consequent impact on cancer establishment and progression.

癌症的发展受到识别并消除恶性转化细胞的效应免疫反应的严格控制。尽管如此,某些免疫亚群,如肿瘤相关巨噬细胞,已被描述为促进肿瘤生长,揭示了免疫系统在癌症中的双重优势作用。细胞应激可以调节免疫细胞和肿瘤细胞之间的串扰,重塑肿瘤免疫原性和/或免疫功能和表型。浸润免疫细胞暴露于肿瘤微环境中典型存在的具有挑战性的条件。作为回报,在应激条件下激活的无数信号通路可能会将平衡推向刺激抗肿瘤反应或免疫介导的肿瘤进展。在此,我们探讨了细胞应激的不同情况如何影响先天免疫和适应性免疫,以及由此对癌症建立和发展的影响。
{"title":"Immunosurveillance of cancer cell stress.","authors":"Seila Lorenzo-Herrero, Christian Sordo-Bahamonde, Segundo González, Alejandro López-Soto","doi":"10.15698/cst2019.09.198","DOIUrl":"10.15698/cst2019.09.198","url":null,"abstract":"<p><p>Cancer development is tightly controlled by effector immune responses that recognize and eliminate malignantly transformed cells. Nonetheless, certain immune subsets, such as tumor-associated macrophages, have been described to promote tumor growth, unraveling a double-edge role of the immune system in cancer. Cell stress can modulate the crosstalk between immune cells and tumor cells, reshaping tumor immunogenicity and/or immune function and phenotype. Infiltrating immune cells are exposed to the challenging conditions typically present in the tumor microenvironment. In return, the myriad of signaling pathways activated in response to stress conditions may tip the balance toward stimulation of antitumor responses or immune-mediated tumor progression. Here, we explore how distinct situations of cellular stress influence innate and adaptive immunity and the consequent impact on cancer establishment and progression.</p>","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2019-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6732214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43622671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Myelopoiesis, metabolism and therapy: a crucial crossroads in cancer progression 骨髓生成、代谢和治疗:癌症进展的关键十字路口
IF 6.4 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2019-07-01 DOI: 10.15698/cst2019.09.197
A. Sica, V. Guarneri, A. Gennari
Cancers promote immunological stresses that induce alterations of the myelopoietic output, defined as emergency myelopoiesis, which lead to the generation of different myeloid populations endowed with tumor-promoting activities. New evidence indicates that acquisition of this tumor-promoting phenotype by myeloid cells is the result of a multistep process, encompassing initial events originating into the bone marrow and later steps operating in the tumor microenvironment. The careful characterization of these sequential mechanisms is likely to offer new potential therapeutic opportunities. Here, we describe relevant mechanisms of myeloid cells reprogramming that instate immune dysfunctions and limit effective responses to anticancer therapy and discuss the influence that metabolic events, as well as chemotherapy, elicit on such events.
癌症促进免疫应激,诱导骨髓输出的改变,定义为紧急骨髓生成,导致产生具有促肿瘤活性的不同骨髓群。新的证据表明,骨髓细胞获得这种促肿瘤表型是一个多步骤过程的结果,包括起源于骨髓的初始事件和在肿瘤微环境中操作的后续步骤。这些顺序机制的仔细表征可能提供新的潜在治疗机会。在这里,我们描述了骨髓细胞重编程的相关机制,这些机制导致免疫功能障碍,限制对抗癌治疗的有效反应,并讨论了代谢事件和化疗对这些事件的影响。
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引用次数: 32
Impact of prophylactic TNF blockade in the dual PD-1 and CTLA-4 immunotherapy efficacy and toxicity 预防性TNF阻断对PD-1和CTLA-4双重免疫疗法疗效和毒性的影响
IF 6.4 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2019-06-26 DOI: 10.15698/cst2019.07.193
Maite Álvarez, I. Otano, Luna Minute, M. Ochoa, E. Pérez-Ruiz, I. Melero, P. Berraondo
The TNF blockade therapy is currently a well-established treatment option for a variety of autoimmune diseases such as rheumatoid arthritis (RA), psoriasis or Crohn's disease, given the proinflammatory role of TNF in the course of these diseases. Importantly, TNF neutralization is also used for the treatment of corticosteroid-refractory immune-related adverse events (irAEs) induced by the combined anti-PD-1 and anti-CTLA-4 immunotherapy. The manifestation of these toxicities is an important limiting factor for the successful implementation of the inhibitory checkpoint blockade therapy (ICB), restraining its anti-tumor efficacy. In our recent study (Perez-Ruiz et al., Nature 569(7756): 428-432.), we analyzed the potential impact of prophylactic TNF neutralization therapy in the anti-PD1/CTLA-4 efficacy. Through several mouse models, we demonstrated that TNF neutralization ameliorated ICB-exacerbated colitis in addition to improving ICB-dependent anti-tumor efficacy. Similar results were obtained after prophylactic TNF blockade in graft vs host xenografted mouse models with human immune cells, which showed a reduction in colitis and hepatitis. Importantly, there was a preservation of the immunotherapeutic control of xenografted tumors after ICB treatment. Moreover, TNF and TNF-dependent gene expression is upregulated in the colon mucosa from patients affected by colitis as a side effect of ipilimumab and nivolumab. Our results, thus, provide evidence of the successful combination of prophylactic TNF neutralization with ICB therapy strategy to ameliorate toxicities, while keeping or even ameliorating anti-tumor efficacy. The prophylactic TNF blockade strategy is clinically feasible since excellent TNF inhibitors have been approved for the treatment of autoimmunity and are used for the immune-related serious adverse events in immunotherapy.
鉴于TNF在各种自身免疫性疾病(如类风湿性关节炎(RA)、银屑病或克罗恩病)过程中的促炎作用,TNF阻断疗法目前是一种公认的治疗选择。重要的是,TNF中和也用于治疗联合抗PD-1和抗CTLA-4免疫疗法诱导的皮质类固醇难治性免疫相关不良事件(irAE)。这些毒性的表现是抑制性检查点阻断疗法(ICB)成功实施、抑制其抗肿瘤疗效的重要限制因素。在我们最近的研究(Perez Ruiz等人,Nature 569(7756):428-432)中,我们分析了预防性TNF中和治疗对抗PD1/CTLA-4疗效的潜在影响。通过几个小鼠模型,我们证明TNF中和除了改善ICB依赖性抗肿瘤疗效外,还改善了ICB加重的结肠炎。在具有人类免疫细胞的移植物与宿主异种移植小鼠模型中预防性阻断TNF后也获得了类似的结果,其显示结肠炎和肝炎的减少。重要的是,在ICB治疗后,异种移植肿瘤的免疫治疗控制得到了保留。此外,作为易普利木单抗和尼沃单抗的副作用,结肠炎患者结肠粘膜中TNF和TNF依赖性基因表达上调。因此,我们的研究结果为预防性TNF中和与ICB治疗策略的成功结合提供了证据,以改善毒性,同时保持甚至改善抗肿瘤疗效。预防性TNF阻断策略在临床上是可行的,因为优秀的TNF抑制剂已被批准用于治疗自身免疫,并用于免疫治疗中的免疫相关严重不良事件。
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引用次数: 16
Immunometabolic cross-talk in the inflamed heart 炎症心脏的免疫代谢串扰
IF 6.4 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2019-06-07 DOI: 10.15698/cst2019.08.194
F. Marelli-Berg, D. Aksentijević
Inflammatory processes underlie many diseases associated with injury of the heart muscle, including conditions without an obvious inflammatory pathogenic component such as hypertensive and diabetic cardiomyopathy. Persistence of cardiac inflammation can cause irreversible structural and functional deficits. Some are induced by direct damage of the heart muscle by cellular and soluble mediators but also by metabolic adaptations sustained by the inflammatory microenvironment. It is well established that both cardiomyocytes and immune cells undergo metabolic reprogramming in the site of inflammation, which allow them to deal with decreased availability of nutrients and oxygen. However, like in cancer, competition for nutrients and increased production of signalling metabolites such as lactate initiate a metabolic cross-talk between immune cells and cardiomyocytes which, we propose, might tip the balance between resolution of the inflammation versus adverse cardiac remodeling. Here we review our current understanding of the metabolic reprogramming of both heart tissue and immune cells during inflammation, and we discuss potential key mechanisms by which these metabolic responses intersect and influence each other and ultimately define the prognosis of the inflammatory process in the heart.
炎症过程是许多与心肌损伤相关的疾病的基础,包括没有明显炎症致病成分的疾病,如高血压和糖尿病心肌病。心脏炎症的持续会导致不可逆的结构和功能缺陷。有些是由细胞和可溶性介质对心肌的直接损伤引起的,也有由炎症微环境维持的代谢适应引起的。众所周知,心肌细胞和免疫细胞在炎症部位都会经历代谢重编程,这使它们能够应对营养和氧气供应减少的问题。然而,与癌症一样,对营养的竞争和信号代谢产物(如乳酸盐)产生的增加引发了免疫细胞和心肌细胞之间的代谢串扰,我们认为,这可能会打破炎症解决与不良心脏重塑之间的平衡。在这里,我们回顾了我们目前对炎症期间心脏组织和免疫细胞代谢重编程的理解,并讨论了这些代谢反应相互交叉和影响的潜在关键机制,最终确定了心脏炎症过程的预后。
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引用次数: 16
The role of epigenetics in hypothalamic energy balance control: implications for obesity 表观遗传学在下丘脑能量平衡控制中的作用:对肥胖的影响
IF 6.4 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2019-06-05 DOI: 10.15698/cst2019.07.191
A. Obri, M. Claret
Despite enormous social and scientific efforts, obesity rates continue to increase worldwide. While genetic factors contribute to obesity development, genetics alone cannot explain the current epidemic. Obesity is essentially the consequence of complex genetic-environmental interactions. Evidence suggests that contemporary lifestyles trigger epigenetic changes, which can dysregulate energy balance and thus contribute to obesity. The hypothalamus plays a pivotal role in the regulation of body weight, through a sophisticated network of neuronal systems. Alterations in the activity of these neuronal pathways have been implicated in the pathophysiology of obesity. Here, we review the current knowledge on the central control of energy balance with a focus on recent studies linking epigenetic mechanisms in the hypothalamus to the development of obesity and metabolic disorders.
尽管做出了巨大的社会和科学努力,全世界的肥胖率仍在继续上升。虽然遗传因素有助于肥胖的发展,但仅靠遗传学并不能解释目前的流行。肥胖本质上是复杂的遗传环境相互作用的结果。有证据表明,当代生活方式会引发表观遗传学变化,从而失调能量平衡,从而导致肥胖。下丘脑通过复杂的神经元系统网络在调节体重方面发挥着关键作用。这些神经元通路活性的改变与肥胖的病理生理学有关。在这里,我们回顾了目前关于能量平衡中央控制的知识,重点是最近将下丘脑的表观遗传学机制与肥胖和代谢紊乱的发展联系起来的研究。
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引用次数: 19
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