白色脂肪"棕色化"调控因子FNDC5/Irisin的研究进展

肥胖是当下全球牵涉范围最广的慢性疾病,也是2型糖尿病、心脑血管疾病以及某些癌症的重要风险因素.其中"白色脂肪棕色化"是目前该领域研究的热点之一,即将体内的储存多余能量的白色脂肪组织(white adipose tissue,WAT)转变为促进消耗能量的棕色脂肪组织(brown adipose tissue,BAT).近年在肌细胞中发现的Ⅲ型纤连蛋白组件包含蛋白5(fibronectin typeⅢdomain containing 5,FNDC5)经胞外切除形成小分子多肽,名为Irisin,具有"白色脂肪棕色化"的功能.     

Ⅱ型固有淋巴细胞在特应性皮炎中作用机制的研究进展

Ⅱ型固有淋巴细胞(typeⅡinnate lymphoid cell,ILC2)是一种新型的固有淋巴细胞群体,活化后可以分泌大量的Th2型细胞因子IL-5、IL-13,主要介导Ⅱ型免疫应答,在抵御寄生虫感染、呼吸道疾病和组织修复中发挥了重要作用。特应性皮炎(atopic dermatitis,AD)是一种慢性复发性皮肤疾病,急性期病理过程主要表现为Th2细胞所介导的Ⅱ型免疫反应。近来发现,ILC2大量存在于人类皮肤的真皮层中,在AD患者的病损皮肤中数量增加并且呈现激活状态,提示ILC2参与了AD的发生发展过程。本文就ILC2在AD中作用机制的研究进展做一综述。     

Th17和Th9细胞参与自身免疫性疾病病理机制研究进展

CD4+T细胞具有抗原识别特异性,是主要组织相容性复合物Ⅱ类分子限制性T细胞。CD4+T细胞受到抗原刺激而活化,活化后的效应T细胞根据产生细胞因子种类和生物学功能的不同,可以分为辅助性T细胞1型(Thelp cell 1,Th1)、2型(Thelpcell 2,Th2)和调节性T细胞(regulatory Tcells,Treg)。Th1细胞主要产生γ干扰素(Interferon-γ,IFN-γ)、白细胞介素2(Interleukin-2,IL-2)和肿瘤坏死因子β(Tumor necrosis factorβ,TNF-β),参与细胞免疫和迟发     

Galectin-9对活化的CD4+T细胞免疫调节作用的机制研究

目的 研究Galectin-9对活化的CD4+T细胞的免疫调节作用,并进一步探讨其作用机制.方法 获取野生型C57BL/6小鼠淋巴细胞,利用MACS分选CD4+ na(i)ve T细胞,给予anti-CD3 (2.5 μg/ml)抗体、anti-CD28(5μg/ml)抗体和IL-2(100 ng/ml)刺激,培养3d.将活化的CD4+T细胞分为3组:正常对照组、Galectin-9组和Galectin-9+α-乳糖组.利用CFSE检测T细胞增殖情况,并动态观察细胞形态变化;检测CD4+ CD69+T细胞、Th1、Th2和Th17细胞的比例;并利用ELISA检测淋巴细胞分泌IFN-γ 、IL-4、IL-10、IL-12、IL-17A和TGF-β1等细胞因子的水平;利用Western blot检测T-bet、GATA-3和ROR-yt等T细胞分化调控蛋白的变化.结果 与正常对照组和Galectin-9+α-乳糖组相比,Galectin-9组于2h时开始出现细胞形态改变,同时CD4+ CD69+T细胞、Th1和Th17细胞表达减少(P＜0.05),但Th2细胞无明显变化;培养上清液中IFN-γ、IL-12、IL-17A和TGF-β1的表达水平降低(P＜0.05),而IL-4和IL-10等Th2型细胞因子水平无明显变化;同时T-bet和ROR-γt的表达水平减少(P＜0.05).结论 Galectin-9抑制活化CD4+T细胞的Th1和Th17型免疫应答,而对Th2型免疫应答无影响,免疫调节的机制可能与其在转录水平影响Th1和Th17特定转录因子的表达有关.     

Th9细胞亚群在变应性鼻炎中的研究进展

CD4+ T辅助细胞包括T辅助细胞1型(Th1)、Th2、Th17和Treg等。Th2细胞在变应性疾病中的重要免疫作用一直得到了较广泛认可。IL-9也一直被视为一种Th2型细胞因子,在变态反应中贡献突出。最近的研究发现了一种独特的产IL-9的CD4+ T辅助细胞,这种新型亚群被命名为Th9细胞亚群,其在变应性鼻炎中的作用研究还很少,本文将就Th9细胞以及其产生的特异性细胞因子IL-9在变应性鼻炎中的研究进展做以阐述。     

Th17／Treg失衡在多发性硬化发病和治疗中的意义

辅助性T细胞17型(helper T-cell type 17,Th17)是产生IL-17的T细胞亚群,国内外已有大量文献证实其与自身免疫病如多发性硬化(Multiple sclerosis,MS)等发病关系密切.调节性T细胞(Regulatory T lymphocyte,Treg)则在体内执行免疫抑制功能,限制过度及错误的免疫应答.Th17/Treg平衡对维持正常免疫应答,防止自身免疫具有重要意义.而在MS中,平衡向Th17倾斜,Th17功能亢进,Treg功能低下.深入研究Th17/Treg平衡、失衡机制,揭示其对发病和治疗的意义,对MS的病理机制研究及诊治具有重要价值.     

免疫调节剂对哮喘的免疫治疗作用

哮喘是一种慢性气道炎症性疾病,免疫机制是哮喘的重要发病机制之一,研究表明Th细胞是哮喘各种临床表现的重要启动和调控因子。Th1细胞亚群比例失调,即Th1/Th2细胞因子平衡偏移在发病机制中占主导地位。当机体初次接触过敏原时,抗原提呈细胞提呈的抗原和细胞因子共同作用于Th0细胞,Th0细胞接收到信号后可分化为Th1、Th2、Th17或调节性T细胞。活化的辅助性T细胞(主要是Th2细胞)产生白介素(IL)如IL-4、IL-5、IL-9、IL-13等Th2型细胞因子,激活包括肥大细胞在内的固有(Resident)炎性细胞,并从血液中募集淋巴细胞、嗜酸性粒细胞及中性粒细胞等其他炎性细胞,释放各种炎性介     

Th17细胞和Treg细胞在人类常见疾病中的表达及相互关系

辅助性17细胞(T help 17 cells,Th17)是近来发现的一种不同于Th1型和Th2型细胞、产生IL-17的Th细胞亚群,在自身免疫性疾病、感染、肿瘤等疾病中发挥着重要的作用.     

白细胞介素-18在支气管哮喘中的研究进展

白细胞介素(interleukin,IL)-18是一种特殊的细胞因子,既能诱导Th1型免疫应答,又能诱导Th2型免疫应答,从而参与许多慢性炎症和自身免疫性疾病炎性反应。支气管哮喘是一种Th1/Th2失衡,由多种细胞(嗜酸性粒细胞、T细胞、肥大细胞等)和多种细胞因子(IL-4、IL-5、IL-13等)参与,以支气管壁的结构改变、气道高反应性为特征的肺部慢性炎症性疾病。IL-18在哮喘的不同发病阶段有不同的作用机制,扮演着重要角色。IL-18能诱导γ干扰素形成,从而促进Th1细胞免疫反应,调节Th1/Th2平衡,IL-18还通过上调Treg细胞的生成对哮喘起保护作用。而有些情况下,IL-18及其促分泌的Th1细胞因子又能加重Th2型反应和气道炎症,使哮喘恶化。     

Th9、Th17及Th22相关细胞因子与2型糖尿病患者并发骨质疏松症的关系

目的探讨辅助性T细胞9(Th9)、Th17及Th22相关细胞因子白细胞介素-9(IL-9)、IL-17及IL-22与2型糖尿病(T2DM)患者并发骨质疏松症(OP)的关系。方法选取2020年4月-2023年2月在长治医学院附属和济医院、和平医院内分泌科及长治市潞州区东街街道社区卫生服务中心就诊的104例T2DM并发OP患者作为并发组, 另选取同期60例单纯T2DM患者作为单纯T2DM组。采用双能X线检测两组L1～4椎体骨密度(BMD)值;采用流式细胞仪检测两组外周血中Th9、Th17及Th22细胞水平;采用酶联免疫吸附法(ELISA)检测两组血清IL-9、IL-17、IL-22水平。经Pearson相关系数分析T2DM并发OP患者外周血中IL-9、IL-17、IL-22水平与骨密度的相关性;以多因素Logistic回归分析T2DM患者并发OP的独立危险因素。结果 Pearson相关性分析显示, T2DM并发OP患者血清中IL-9、IL-17、IL-22与骨密度均呈负相关(r=-0.337, -0.459, -0.310, P<0.001);多因素Logistic回归分析结果显示,...     

大鼠白色和棕色脂肪来源的间充质干细胞成脂分化特性的比较

目的探讨白色脂肪组织(WAT)和棕色脂肪组织(BAT)来源的间充质干细胞成脂分化特性的差异。方法雄性SD大鼠15只,3只用于细胞分离培养,12只用于细胞移植。体外分离培养WAT和BAT两种来源的脂肪干细胞,用油红O染色检测两种干细胞的成脂分化率,用免疫荧光技术检测成脂诱导、分化后的细胞是棕色脂肪细胞还是白色脂肪细胞。4’6-二脒基-2-苯基吲哚(DAPI)标记两种来源的干细胞后移植至腹股沟区,分别在第1、2、3周取材,免疫荧光技术检测植入细胞的分化趋向。结果 WAT来源的干细胞增殖速度明显快于BAT来源的干细胞,前者成脂分化率为0.205±0.069,后者为0.165±0.053,两种干细胞的成脂诱导率差异无统计学意义(P0.05)。两种干细胞分别植入体内后,在第1、2、3周发现,两种干细胞均表达棕色脂肪特异性蛋白解耦联蛋白1(UCP1)。结论 WAT和BAT来源的干细胞在体外及体内诱导成脂后均分化为棕色脂肪细胞。     

Alpha-syntrophin deficient mice are protected from adipocyte hypertrophy and ectopic triglyceride deposition in obesity

Alpha-syntrophin (SNTA) is a molecular adapter protein which is expressed in adipocytes. Knock-down of SNTA in 3T3-L1 preadipocytes increases cell proliferation, and differentiated adipocytes display small lipid droplets. These effects are both characteristics of healthy adipose tissue growth which is associated with metabolic improvements in obesity. To evaluate a role of SNTA in adipose tissue morphology and obesity associated metabolic dysfunction, SNTA deficient mice were fed a standard chow or a high fat diet. Mice deficient of SNTA had less fat mass and smaller adipocytes in obesity when compared to control animals. Accordingly, these animals did not develop liver steatosis and did not store excess triglycerides in skeletal muscle upon high fat diet feeding. SNTA?/? animals were protected from hyperinsulinemia and hepatic insulin resistance. Of note, body-weight, food uptake, and serum lipids were normal in the SNTA null mice. SNTA was induced in adipose tissues but not in the liver of diet induced obese and ob/ob mice. In human subcutaneous and visceral fat of seven patients SNTA was similarly expressed and was not associated with body mass index. Current data demonstrate beneficial effects of SNTA deficiency in obesity which is partly attributed to smaller adipocytes and reduced white adipose tissue mass. Higher SNTA protein in fat depots of obese mice may contribute to adipose tissue hypertrophy and ectopic lipid deposition which has to be confirmed in humans.     

醉茄素A通过诱导白色脂肪组织褐变抵御高脂饮食诱导的肥胖

目的 探索醉茄素A对高脂饮食诱导肥胖的抵抗作用及其作用机制。方法 8周龄C57BL/6 J小鼠分为醉茄素A组和对照组,每组10只,高脂饮食（HFD）饲养,分别给予醉茄素A或对照溶剂DMSO腹腔注射,每天测量小鼠体重及摄食量。1周后取材,称量小鼠腹股沟白色脂肪（iWAT）、附睾白色脂肪（eWAT）、腹膜后白色脂肪（rWAT）和肩胛间棕色脂肪（BAT）的重量;取iWAT检测褐变相关因子表达水平;HE染色观察iWAT细胞形态变化。结果 醉茄素A组小鼠的体重和各部位脂肪组织重量均显著低于对照组,摄食量无明显变化;Real-time PCR显示,醉茄素A组小鼠iWAT中褐变相关基因表达水平显著提高;Western blotting结果表明,醉茄素A组小鼠iWAT中解耦联蛋白1（UCP1）和过氧化物酶体增殖体激活受体γ共激活因子1α（PGC1α）表达明显增加;HE染色与免疫荧光结果显示,醉茄素A组小鼠腹股沟白色脂肪细胞呈现典型褐变特征,如脂肪细胞多腔室化。结论 醉茄素A可能通过诱导小鼠白色脂肪组织褐变抵御高脂饮食诱导的肥胖。     

Effects of Eucommia leaf extracts on autonomic nerves,body temperature,lipolysis, food intake,and body weight

Eucommia ulmoides Oliver leaf extracts (ELE) have been shown to exert a hypolipidemic effect in hamsters. Therefore, it was hypothesized that ELE might affect lipid metabolism via changes in autonomic nerve activities and causes changes in thermogenesis and body weight. We examined this hypothesis, and found that intraduodenal (ID) injection of ELE elevated epididymal white adipose tissue sympathetic nerve activity (WAT-SNA) and interscapular brown adipose tissue sympathetic nerve activity (BAT-SNA) in urethane-anesthetized rats and elevated the plasma concentration of free fatty acids (FFA) (a marker of lipolysis) and body temperature (BT) (a marker of thermogenesis) in conscious rats. Furthermore, it was observed that ID administration of ELE decreased gastric vagal nerve activity (GVNA) in urethane-anesthetized rats, and that ELE given as food reduced food intake, body and abdominal adipose tissue weights and decreased plasma triglyceride level. These findings suggest that ELE stimulates lipolysis and thermogenesis through elevations in WAT-SNA and BAT-SNA, respectively, suppresses appetite by inhibiting the activities of the parasympathetic nerves innervating the gastrointestinal tract, including GVNA, and decreases the amount of abdominal fat and body weight via these changes.     

Metrnl在肥胖小鼠模型中的表达

目的:探讨肥胖对小鼠各组织中Metrnl表达的影响。方法:高脂饮食4个月诱导小鼠肥胖,实时定量PCR与免疫组织化学法检测正常饮食与高脂饮食小鼠肝、骨骼肌、肾、结肠及脂肪组织中Metrnl mRNA与蛋白的表达。结果:高脂饮食增加了小鼠的体质量和白色脂肪量。同时,高脂饮食显著增加了白色脂肪组织Metrnl mRNA与蛋白的水平,但未增加肝、骨骼肌、肾、结肠组织中Metrnl的表达。结论:肥胖特异性增加脂肪组织中Metrnl的表达,从而形成"肥胖-脂肪组织上调Metrnl表达-代谢改善"的反馈调节通路。     

Aging adipose: Depot location dictates age-associated expansion and dysfunction

Adipose tissue has a variety of diverse functions that maintain energy homeostasis. In conditions of excess energy availability, adipose tissue increases its lipid storage and communicates the nutritional abundance to various organs in the body. In conditions of energy depletion, such as fasting, cold exposure, or prolonged exercise, triglycerides stored in adipose tissue are released as free fatty acids to support the shift to catabolic metabolism. These diverse functions of storage, communication, and energy homeostasis are shared between numerous adipose depots including subcutaneous, visceral, brown, beige, intramuscular, marrow, and dermal adipose tissue. As organisms age, the cellular composition of these depots shifts to facilitate increased inflammatory cell infiltration, decreased vasculature, and increased adipocyte quantity and lipid droplet size. The purpose of this review is to give a comprehensive overview of the molecular and cellular changes that occur in various aged adipose depots and discuss their impact on physiology. The molecular signature of aged adipose leads to higher prevalence of metabolic disease in aged populations including type 2 diabetes, cardiovascular disease, Alzheimer’s disease, and certain types of cancer.     

Comparison of DNA synthesis in white and brown adipose tissue in rats with ventromedial hypothalamic lesions

Ventromedial hypothalamic (VMH) lesions cause excessive fat accumulation in white adipose tissue (WAT), and brown adipose tissue (BAT); however, little information is available on whether or not cell proliferation occurs in WAT and BAT after VMH lesioning. In this study, we determined the DNA content and thymidine incorporation in unilateral parametrial WAT and interscapular BAT 0, 1, 3, and 7 days after VMH lesioning, and examined the mechanism of increased DNA content in WAT. In rats with VMH lesions, the weight of WAT and BAT had increased significantly at 7 days, and the DNA content and thymidine incorporation of WAT had increased significantly at 3 days and continued to increase for up to 7 days, while those of BAT did not increase for as long as 7 days after VMH lesioning. Restricted food intake according to the pair-feeding method partially inhibited the increased DNA content in WAT. The increased DNA content in WAT was mostly restored but not completely by the administration of anti-insulin antibody, and by administration of propranolol, a -adrenergic blocker. The results demonstrated that VMH lesions induced DNA synthesis in WAT early after VMH lesioning, but did not induce DNA synthesis in BAT, and suggested that either hyperinsulinemia or a -adrenergic receptor mechanism or both may be responsible for the increased DNA content in WAT.     

Metabolic regulation by PPARγ is required for IL-33-mediated activation of ILC2s in lung and adipose tissue

Type 2 innate lymphoid cells (ILC2s) play a critical role early in the response to infection by helminths and in the development of allergic reactions. ILC2s are also involved in the physiologic regulation of adipose tissue and its metabolic response to cold shock. We find that the metabolic sensor peroxisome proliferator-activated receptor gamma (PPARγ) is highly expressed in ILC2s of the lung and adipose tissue and increases responsiveness to IL-33. In turn, activation of ILC2 by IL-33 leads to increased expression of PPARγ, a prerequisite for proliferation and expression of the effector cytokines IL-5 and IL-13. In contrast, pharmacological inhibition of PPARγ leads to decreased expression of CD36 and fatty acid uptake, a necessary source of energy for ILC2s and of potential ligands for PPARγ. As a consequence, treatment of mice with a PPARγ antagonist reduces the severity of an ILC2-dependent acute airway inflammation. Together, our results demonstrate the critical role of the metabolic sensor PPARγ for the functions of ILC2s.     

Structural and biochemical characteristics of various white adipose tissue depots

It is now widely accepted that white adipose tissue (WAT) is not merely a fuel storage organ, but also a key component of metabolic homoeostatic mechanisms. Apart from its major role in lipid and glucose metabolism, adipose tissue is also involved in a wide array of other biological processes. The hormones and adipokines, as well as other biologically active agents released from fat cells, affect many physiological and pathological processes. WAT is neither uniform nor inflexible because it undergoes constant remodelling, adapting the size and number of adipocytes to changes in nutrients' availability and hormonal milieu. Fat depots from different areas of the body display distinct structural and functional properties and have disparate roles in pathology. The two major types of WAT are visceral fat, localized within the abdominal cavity and mediastinum, and subcutaneous fat in the hypodermis. Visceral obesity correlates with increased risk of insulin resistance and cardiovascular diseases, while increase of subcutaneous fat is associated with favourable plasma lipid profiles. Visceral adipocytes show higher lipogenic and lipolytic activities and produce more pro-inflammatory cytokines, while subcutaneous adipocytes are the main source of leptin and adiponectin. Moreover, adipose tissue associated with skeletal muscles (intramyocellular and intermuscular fat) and with the epicardium is believed to provide fuels for skeletal and cardiac muscle contraction. However, increased mass of either epicardial or intermuscular adipose tissue correlates with cardiovascular risk, while the presence of the intramyocellular fat is a risk factor for the development of insulin resistance. This review summarizes results of mainly human studies related to the differential characteristics of various WAT depots.