脂肪组织与大脑对话——杰出科学成就奖获奖演说介绍

体重在下丘脑摄食/饱食中枢的调节下保持精确的平衡,瘦素在其中发挥重要的作用.当脂肪组织增多时,瘦素分泌也增加,从而抑制摄食中楸减少摄入,获得新的平衡.而在肥胖的动物,由于瘦素抵抗,这种平衡被打破.这可能与脂肪酸作为内源性的过氧化物酶体增殖物活化受体γ激动剂导致中枢瘦素抵抗有关.脂肪组织的扩张与其可塑性有关,后者与微血管增生有关,抑制微血管增生的促凋亡肽可抑制脂肪的扩张,同时通过脂肪组织发出的某种信号,导致摄食减少,为肥胖的治疗提供了新的思路.     

瘦素信号转导系统对卵巢功能的影响

通过卵巢交互移植,构建实验小鼠的瘦素长受体(LR)基因型组合分别为A(躯体LR+,卵巢LR-)、B(躯体LR+,卵巢LR+)、C(躯体LR-,卵巢LR+)、D(躯体LR-,卵巢LR-)共4组(A组n=10、余皆n=5).与A、B组比较,C、D组糖脂代谢水平及卵巢功能各项指标之间均存在显著差异.证实卵巢内存在完整的瘦素信号转导系统;卵巢局部瘦素信号转导缺失并小影响卵巢自身的生殖功能.     

瘦素及其信号通路促肝纤维化机制研究进展

多种慢性肝病能导致肝纤维化,肝纤维化是发展为肝硬化的中间阶段。肝星状细胞的激活在肝纤维化的发生发展中起关键作用。在各种炎症刺激下,体内促肝纤维化因子激活其信号转导通路,使肝星状细胞的形态和功能发生变化,引起胶原沉积。瘦素作为一种促肝纤维化因子,通过其信号转导机制在肝纤维化发生发展中发挥重要作用。     

红斑狼疮患者瘦素及可溶性瘦素受体检测的临床意义

目的探讨血清瘦素（Lp）和可溶性瘦素受体（sLR）与不同临床分型的红斑狼疮（LE）及系统性红斑狼疮（SLE）病情活动程度的关系。方法于2004年6月至2005年12月对中国医科大学附属第二医院和中国医科大学附属第一医院的39例LE患者，同年龄、性别、体重指数（BMI）均相匹配的31名健康人对照，采用放射免疫法和酶联免疫吸附实验（ELISA）检测血清Lp和sLR水平。结果（1）与正常对照相比较，LE患者血清Lp水平增高和sLR水平下降，差异有统计学意义（P〈0．01），活动期SLE患者血清Lp水平增高和sLR水平下降尤为显著；但非活动期SLE、亚急性皮肤型红斑狼疮（SCLE）和盘状红斑狼疮（DLE）患者血清Lp和sLR水平差异无统计学意义（P〉0．05）。（2）Lp与BMI呈正相关，与sLR呈负相关；SLE患者的病情活动程度与血清Lp水平呈正相关，与sLR水平呈负相关（P〈0．01）。结论Lp和sLR水平异常可能与LE的发病密切相关     

红斑狼疮患者瘦素及可溶性瘦素受体检测的临床意义

目的探讨血清瘦素(Lp)和可溶性瘦素受体(sLR)与不同临床分型的红斑狼疮(LE)及系统性红斑狼疮(SLE)病情活动程度的关系。方法于2004年6月至2005年12月对中国医科大学附属第二医院和中国医科大学附属第一医院的39例LE患者,同年龄、性别、体重指数(BMI)均相匹配的31名健康人对照,采用放射免疫法和酶联免疫吸附实验(ELISA)检测血清Lp和sLR水平。结果(1)与正常对照相比较,LE患者血清Lp水平增高和sLR水平下降,差异有统计学意义(P<0.01),活动期SLE患者血清Lp水平增高和sLR水平下降尤为显著;但非活动期SLE、亚急性皮肤型红斑狼疮(SCLE)和盘状红斑狼疮(DLE)患者血清Lp和sLR水平差异无统计学意义(P>0.05)。(2)Lp与BMI呈正相关,与sLR呈负相关;SLE患者的病情活动程度与血清Lp水平呈正相关,与sLR水平呈负相关(P<0.01)。结论Lp和sLR水平异常可能与LE的发病密切相关。     

瘦素及瘦素功能性受体表达与大鼠肝硬化关系的研究

目的观察实验性大鼠肝硬化形成过程中,肝组织瘦素及瘦素功能性受体表达的动态变化以及与肝内胶原含量的关系。方法经皮下注射四氯化碳(0.3ml/100g体重,每周2次)复制肝硬化动物模型,于第0、3、6、9、12周各处死一批大鼠。用RT-PCR检测各期动物肝组织中瘦素及瘦素功能性受体(Ob-Rb)mRNA表达水平。用免疫组织化学方法检测各期动物肝组织中瘦素、瘦素受体的表碉和定位,用放射免疫法检测各期动物血浆中透明质酸(HA)、瘦素水平。运用MPIAS-500多媒体真彩色图像分析系统作肝内胶原定量分析。结果正常肝组织中有少量瘦素、瘦素功能性受体的mRNA表达,随着肝硬化的形成,各期表达量逐渐递增(与0周比较,P<0.01)。正常肝组织可见瘦素及瘦素受体在血管周围、汇管区及肝索间质细胞的细胞质和细胞膜有少量表达,随着肝硬化的形成,瘦素、瘦素受体表达增多、增强(P<0.01)。随着造模时间的增加,肝内胶原面积、血浆中HA和瘦素均逐渐增加,各期比较差异有统计学意义(P<0.05)。肝硬化形成过程中,肝脏中瘦素、瘦素功能性受体的mRNA表达水平与血浆中HA水平及肝内胶原含量呈正相关(瘦素与HA:r=0.726,P=0.00;瘦素与胶原:r=0.732,P=0.00;Ob-Rb与HA:r=0.705,P=0.00;Ob-Rb与胶原:r=0.764,P=0.00)。结论在四氯化碳诱导的大鼠肝硬化形成过程中,瘦素及功能性受体的基因和蛋白表达增加,并随肝硬化程度的加重而逐步升高,从而促进肝硬化的发生。     

高血压患者血浆瘦素及其可溶性瘦素受体水平的相关性研究

目的:探讨原发性高血压患者血浆瘦素及其可溶性瘦素受体水平的变化及其在高血压发生、发展中的作用。方法:选择2008-10-2009-07在我科住院的原发性高血压患者180例,男女各90例,门诊60例体检正常者作为对照组。采用酶联免疫法测定瘦素及其可溶性瘦素受体浓度,同时测定空腹血糖、三酰甘油、高密度脂蛋白、低密度脂蛋白、体质指数、腰臀比等指标,分析血浆瘦素及其可溶性瘦素受体与原发性高血压的关系。结果:高血压组患者血浆瘦素水平明显高于对照组(12.217±6.10∶8.89±5.27,P0.01),可溶性瘦素受体水平低于对照组(124.08±62.12∶164.23±69.60,P0.01)。且与正常对照组相比,随着血压水平的升高,血浆瘦素水平也明显升高,可溶性瘦素受体水平呈下降趋势。结论:原发性高血压患者的血浆瘦素浓度升高,可溶性瘦素受体浓度下降,与血压之间具有一定的相关性,说明瘦素抵抗与高血压的发生和发展密切相关。     

瘦素与胃排空

瘦素(leptin)是一种主要由白色脂肪组织分泌的蛋白类激素。在调节摄食、体重、能量消耗和神经内分泌方面发挥着重要的作用。最近研究表明,瘦素可以改变胃肠神经肌肉的反应性,调节胃排空。除了调节能量代谢平衡等作用,还有抑制摄食、抑制胃排空和调节胃肠激素的分泌作用。提示,瘦素是与胃肠的生理功能及胃肠疾病密切相关的一种新的胃肠激素。     

瘦素及瘦素受体与非酒精性脂肪肝病的关系

目的 通过检测非酒精性脂肪肝病(NAFLD)患者血清瘦素、肝组织瘦素(Lp)及瘦素受体(OB-R)的水平,探讨瘦素及瘦素受体在NAFLD发病机制中的可能作用.方法 应用放免及免疫组织化学方法检测30例NAFLD患者及30例对照者血清Lp、肝组织中Lp及OB-R水平,并检测空腹血糖、总胆固醇、甘油三脂、C-肽、胰岛素、体...     

冠心病患者血清瘦素及可溶性瘦素受体检测分析

目的:研究血清瘦素(Lp)及可溶性瘦素受体(sLR)水平与冠心病的关系。方法:应用放射免疫分析法(RIA)及酶联免疫吸附分析法(ELISA)检测34例冠心病患者及其36例对照者血清Lp、sLR、空腹血糖(FBG)、TC、TG、HDL、LDL、胰岛素(INS)、稳态模型(HOMA)评估胰岛素抵抗(IR)(HOMA-IR)、体质指数(BMI)、腰围、臀围、腰臀比(WHR)等临床指标,分析Lp、sLR与血脂、IR及冠心病的关系。结果:冠心病组Lp、INS及HOMA-IR水平明显高于对照组,sLR水平明显低于对照组(P<0.01)。Lp与BMI、腰围、臀围、INS、HOMA-IR、TC、TG呈正相关,与sLR呈负相关;sLR与Lp、BMI、腰围、臀围呈负相关(P<0.05或P<0.01)。结论:Lp及sLR异常与肥胖、血脂异常、IR密切相关,共同参与冠心病的发生发展。     

Behavioral and physiological effects of photoperiod-induced migratory state and leptin on a migratory bird, Zonotrichia albicollis: I. Anorectic effects of leptin administration

The hormone leptin is involved in the regulation of energy balance in mammals, mainly by reducing food intake and body adiposity and increasing energy expenditure. During energetically demanding periods, leptin’s action is often altered to facilitate fat deposition and maintain high rates of food intake. Despite the present controversy over the existence of an avian leptin, there is evidence that a leptin receptor exists in birds and its activation influences energy intake and metabolism. However, it is unknown whether the effects of the activation of leptin receptor on energy balance are modulated during migration. We manipulated photoperiod to induce migratory behavior in captive white-throated sparrows (Zonotrichia albicollis) and injected migratory and wintering sparrows with either murine leptin or PBS for 7 days. We measured food intake, changes in body composition and foraging behavior to test if leptin’s effects are altered during migratory state. Leptin decreased foraging behavior, food intake and fat mass in wintering sparrows, but had no effect on foraging behavior or food intake in migratory sparrows. Migratory sparrows injected with leptin maintained fat better than sparrows injected with PBS. Thus, sparrows’ responses to leptin changed with migratory state, possibly to aid in the increase and maintenance of rates of food intake and fat deposition. We also found that long-form leptin receptor and SOCS3 were expressed in tissues of sparrows, including the hypothalamus, but their expression did not change with migratory state. Further study of the leptin receptor system and other regulators of energy balance in migratory birds will increase our understanding of the physiological mechanisms that are responsible for their ability to complete energetically demanding journeys.     

瘦素及其受体在肝癌组织中的表达及意义

目的研究瘦素及其受体在原发性肝细胞性肝癌组织中的表达，并探讨其在肝癌发生过程中的可能作用。方法采用免疫组织化学染色法检测60例原发性肝细胞性肝癌及其对应的癌旁组织中瘦素和瘦素受体蛋白的表达，并就其表达与临床病理组织学参数之间的关系进行分析。结果60例肝癌组织中瘦素及其受体的表达率分别为83．33％（50／60）和76．67％（46／60），癌旁组织中瘦素及其受体的表达率分别为23．33％（14／60）和33．33％（20／60），两者相比差异有统计学意义。但瘦素及其受体的表达与患者年龄、性别、肿瘤大小、组织学分级、TNM分期差异无统计学意义。结论瘦素及其受体以双重表达方式存在于肝癌组织中，可能在原发性肝细胞性肝癌的早期发生中起到一定作用。     

阻塞性睡眠呼吸暂停低通气综合征与血清瘦素水平的关系

阻塞性睡眠呼吸暂停低通气综合征(OSAHS)是一种呼吸系统常见病,近年为临床所日益关注.瘦素作为一个与多器官系统功能有关的激素,参与人体的多项生理过程和病理生理改变,与人的呼吸功能有着密切的联系,在OSAHS中也可能起着重要的作用.本文综述了近年来OSAHS与瘦素关系的研究进展.     

Lean heart: Role of leptin in cardiac hypertrophy and metabolism

Leptin is an adipokine that has been linked with the cardiovascular complications resulting from obesity such as hypertension and heart disease. Obese patients have high levels of circulating leptin due to increased fat mass. Clinical and population studies have correlated high levels of circulating leptin with the development of cardiac hypertrophy in obesity. Leptin has also been demonstrated to increase the growth of cultured cardiomyocytes. However, several animal studies of obese leptin deficient mice have not supported a role for leptin in promoting cardiac hypertrophy so the role of leptin in this pathological process remains unclear. Leptin is also an important hormone in the regulation of cardiac metabolism where it supports oxidation of glucose and fatty acids. In addition, leptin plays a critical role in protecting the heart from excess lipid accumulation and the formation of toxic lipids in obesity a condition known as cardiac lipotoxicity. This paper focuses on the data supporting and refuting leptin’s role in promoting cardiac hypertrophy as well as its important role in the regulation of cardiac metabolism and protection against cardiac lipotoxicity.     

瘦素及其受体与原发性肝癌关系的初步研究

原发性肝细胞性肝癌是严重威胁人类健康的消化系统恶性肿瘤。肝癌组织以及肝癌细胞株是否存在瘦素及瘦素受体的表达是认识瘦素是否参与肝癌发病机制的基础。本研究采用免疫组织化学的方法检测原发性肝细胞性肝癌及其癌旁组织中瘦素及瘦素受体蛋白的表达，并以逆转录聚合酶链反应（RTPCR）半定量分析人肝细胞癌细胞株SMMC-7721和人正常肝细胞株L02中瘦素及瘦素受体mRNA的表达，旨在为进一步探究瘦素系统与原发性肝细胞性肝癌的关系奠定基础。     

Association between variants in the genes for leptin, leptin receptor, and proopiomelanocortin with chronic heart failure in the Czech population

Patients with chronic heart failure (CHF) express enhanced catabolic metabolism finally resulting in overall weight loss, whereas adipokines might play a crucial role in signaling among tissues. The aim of this study was to investigate the possible associations of defined variability in leptin (dbSNP ID rs7799039), proopiomelanocortin (dbSNP ID rs3754860 and dbSNP ID rs1009388), and leptin receptor gene (dbSNP rs1137101) with CHF and evaluate their potential as the CHF susceptibility genes. The case-control study comprised a total of 372 patients of Caucasian origin with chronic heart failure (New York Heart Association [NYHA] functional classes II–IV, ejection fraction (EF) <40%) and 407 healthy controls. They were genotyped for the leptin (LEP) −2548 G/A, leptin receptor (LEPR) Gln223Arg, and proopiomelanocortin (POMC) RsaI (5′-untranslated region) and C1032G variants (intron 1) using PCR-based methodology. No case-control differences in genotype as well as allele frequencies were observed between CHF patients and controls. We constructed POMC RsaI/C1032G haplotypes, having found no significant association with body mass index (BMI), left ventricle ejection fraction (LVEF), left ventricle hypertrophy (LVH) and diabetes mellitus (DM). Multivariate regression analyses revealed an approximately 2-fold risk for NYHA class IV associated with the LEPR Gln223Arg (P = 0.0000001, odds ratio [OR] = 2.10, 95% confidence interval [CI] = 1.56−2.84); it also displayed an independent prediction role for LVEF in heart failure cases of all etiologies (P = 0.002, OR = 4.05, 95% CI = 1.36−10.06). In subanalyses according to CHF etiology the LEPR Gln223Arg showed an independent prediction role for NYHA IV in IHD patients (P = 0.0001, OR = 2.50, 95% CI = 1.69−3.82) and both for NYHA IV(P = 0.007, OR = 2.04, 95% CI = 1.20−3.84) and LVEF (P = 0.004, OR = 11.87, 95% CI = 2.08−55.6) in DCMP patients. The role of the polymorphic variants in the genes encoding for adipokines as potential CHF susceptibility genes is unclear. Based on our findings, the LEPR Gln223Arg polymorphism could be considered a disease susceptibility modulating factor both in ischemic heart disease or dilated cardiomyopathy patients.