白色脂肪组织在不同类型肥胖和代谢状态人群中的差异及作用

肥胖已日益成为严重的全球性健康问题,大部分肥胖可导致机体一系列代谢异常,此类肥胖被称为代谢异常型肥胖(metabolically unhealthy obesity,MUO);还有一类虽然按体重指数标准被称之为肥胖,但机体代谢水平正常,被称为代谢正常型肥胖(metabolically healthy obesity,M...     

肥大细胞在肺部感染性疾病中的作用

肺部肥大细胞主要分布于肺部血管周围,支气管以及粘膜组织。病原体入侵时,肥大细胞通过胞吞作用直接摄取病原体,同时通过激活自身受体促进下游细胞介质的释放,增强炎性细胞的募集,直接和间接杀伤病原体。此外,肺部肥大细胞参与病原体的抗原递呈,介导细胞和体液免疫。肥大细胞对肺部病原体感染具有重要的保护功能。     

肥大细胞在细菌和病毒感染中的作用

自1878年发现肥大细胞以来,人们对肥大细胞在过敏性疾病中的作用进行了广泛而深入的研究,但对肥大细胞的生理功能却了解不多。从无脊椎动物的昆虫到人类,肥大细胞在生物体的长期进化中能得以保留,说明这种细胞具有不可替代的重要作用。肥大细胞广泛分布于皮肤、呼吸道和胃肠道等易与外界接触的部位,并位于血管周围。这就使得肥大细胞不仅能时刻监视病原菌的入侵,而且肥大细胞所释放的介质和细胞因子也能迅速作用于血管内皮细胞和血液中的炎性细胞,并经血液分布到全身各组织器官中。有关肥大细胞在宿主抵御病原微生物中的作用已引起人们的关注。本综述主要介绍肥大细胞在细菌感染时,对宿主的保护和损伤作用、对细菌识别的分子机制以及肥大细胞与病毒感染等方面的研究进展。     

肥大细胞在慢性肝病发生中的作用

［摘要］ 目的：探讨肥大细胞(mast cell, MC)在慢性肝病中的作用及乙型肝炎病毒（HBV）感染是否引起慢性肝病中MC数量增加。方法：本研究包括正常组(NL)8例、慢性肝炎组(CH)30例、肝硬化组(LC)43例、肝癌组(HCC)49例。采用甲苯胺蓝染色和免疫组织化学染色观察130 例人肝组织中肥大细胞的密度和分布特征。另外，采用免疫组织化学染色定性检测各组HBsAg，HBcAg的表达。结果：各肝病组中（肝炎组、肝硬化组、肝癌组）肥大细胞密度比正常组显著增加 (P<0.05)；肝硬化组、肝癌组中MC密度均比慢性肝炎组显著增加(P<0.05)；但肝硬化组与肝癌组之间差异无统计学意义（P>0.05）。MC分布以结缔组织区域多见。本组病例中肥大细胞密度与HBV感染无关。结论：肥大细胞可能参与慢性肝病发生发展过程并发挥重要作用，但其数量增加可能与HBV感染无直接关系。     

肥大细胞在支气管哮喘中的研究进展

支气管哮喘(哮喘)是呼吸系统的常见病和多发病,肥大细胞是其主要的反应细胞,目前关于肥大细胞在哮喘中作用的研究取得了新的进展,特别是肥大细胞蛋白酶及其抑制剂的深入研究和哮喘患者气道平滑肌束中肥大细胞数量明显增加并呈脱颗粒状态的发现,引起学者们极大的关注,本文将就肥大细胞在哮喘中的研究进展进行综述。     

肥大细胞在辐射后器官纤维化中的作用

用新建立的阿里新蓝－番红花红双染法，抗５－溴脱氧尿苷单抗和图像分析技术，研究肥大细胞在正常和照射大鼠组织内的分布特点及其颗粒活性介质（组胺）对成纤维细胞生长的影响，结果表明了肥大细胞及其亚群在组织内不均匀分布，辐射后的变化趋势以及与辐射后器官纤维化的关系，提示了肥大细胞重要颗粒活性介质－组胺，在辐射后器官纤维化的发生中可能起着不可忽视的作用。     

肥大细胞在感染及免疫中的作用研究进展

既往认为,肥大细胞主要超敏反应特别是在速发型超敏反应中发挥作用,并与许多疾病的病理生理过程有关,近年来发现,肥大细胞在宿主对病原体的防御反应中发挥着重要作用,该细胞除了具有识别,吞噬并杀灭病原微生物的功能外,尚具有加工,提呈抗原及调节机体免疫反应的作用,为此,有必要对肥大细胞的生物学作用进行更深入的研究及重新认识。     

肥大细胞在变态反应性炎症发病机制中的核心作用

变态反应性炎症包括支气管哮喘、变应性鼻炎、变应性皮炎、食物及药物过敏等 ,发病率约占全球人口的 30 % - 4 0 %。由于对人类的危害极大 ,所以于 2 0 0 0年末被世界卫生组织定为四大非传染性疾病项目之一。虽然人类对于此类疾病的认识可追溯到 4 80 0年前 ,但对它们本质的认识直到最近 2 0年才逐渐清楚。这主要得益于生命科学各学科的迅猛发展。例如 ,纤支镜应用于哮喘研究使人们认识到哮喘是一种气道的慢性炎症过程。今天 ,通过对各种炎症性细胞及其介质 ,包括上皮细胞、内皮细胞、成纤维细胞和平滑肌细胞在内的传统“结构”细胞及其分泌…     

人类心外脂肪组织与肥胖患者心血管疾病的关系

近年来,越来越多的证据支持心外膜脂肪组织在结构及功能方面对心血管有着重要的影响,临床实践及动物实验也发现心外膜脂肪组织在心血管疾病的发生中扮演着一定的角色。早期通过影像学检查方法对心外膜脂肪组织进行评估,对避免后续心血管疾病的发生具有一定的临床实践意义。     

肥大细胞在感染及免疫中的作用研究进展

既往认为,肥大细胞主要在超敏反应特别是在速发型超敏反应中发挥作用,并与许多疾病的病理生理过程有关。近年来发现,肥大细胞在宿主对病原体的防御反应中发挥着重要作用。该细胞除了具有识别、吞噬并杀灭病原微生物的功能外,尚具有加工、提呈抗原及调节机体免疫反应的作用。为此,有必要对肥大细胞的生物学作用进行更深入的研究及重新认识。     

Correlation between pancreatic mast cells and the low grade inflammation in adipose tissue of experimental prediabetes

The role of mast cells (MCs) in prediabetes (Pre-DM) is not clearly elucidated. In the current study rats (n?=?22 each) were divided equally into; control and Pre-DM (received high fat diet, HFD) groups. Samples from pancreas as well as from visceral adipose tissue (VAT) were studied for the consequent changes.We detected a significantly increased mast cell count (MCC) in the pancreas of Pre-DM compared to that of control. Frequent degranulation of MC granules was observed in Pre-DM. VAT of the Pre-DM had significantly increased (p?<?0.05) macrophages (CD68⁺) and mast cells (tryptase⁺) compared to that of the control. A significant increase (p?<?0.05) in CD68 mRNA expression as well as in the level of IL-1 β, IL-6, TNF-α and TGF- β1 was detected in VAT of Pre-DM with a significant positive correlation (p?<?0.05) with the MCC. All these findings may indicate a potential role of MC in the low grade inflammation of VAT in Pre-DM.     

Combining decellularized human adipose tissue extracellular matrix and adipose-derived stem cells for adipose tissue engineering

Repair of soft tissue defects resulting from lumpectomy or mastectomy has become an important rehabilitation process for breast cancer patients. This study aimed to provide an adipose tissue engineering platform for soft tissue defect repair by combining decellularized human adipose tissue extracellular matrix (hDAM) and human adipose-derived stem cells (hASCs). To derive hDAM incised human adipose tissues underwent a decellularization process. Effective cell removal and lipid removal were proved by immunohistochemical analysis and DNA quantification. Scanning electron microscopic examination showed a three-dimensional nanofibrous architecture in hDAM. The hDAM included collagen, sulfated glycosaminoglycan, and vascular endothelial growth factor, but lacked major histocompatibility complex antigen I. hASC viability and proliferation on hDAM were proven in vitro. hDAM implanted subcutaneously in Fischer rats did not cause an immunogenic response, and it underwent remodeling, as indicated by host cell infiltration, neovascularization, and adipose tissue formation. Fresh fat grafts (Coleman technique) and engineered fat grafts (hDAM combined with hASCs) were implanted subcutaneously in nude rats. The implanted engineered fat grafts maintained their volume for 8 weeks, and the hASCs contributed to adipose tissue formation. In summary, the combination of hDAM and hASCs provides not only a clinically translatable platform for adipose tissue engineering, but also a vehicle for elucidating fat grafting mechanisms.     

Composition of fatty acids in a high-fat diet affects adipose tissue inflammation by inducing calreticulin on adipocytes and activating group 1 innate lymphoid cells

Obesity-induced adipose tissue inflammation plays a critical role in the development of metabolic diseases. For example, NK1.1⁺ group 1 innate lymphoid cells (G1-ILCs) in adipose tissues are activated in the early stages of inflammation in response to a high-fat diet (HFD). In this study, we examined whether the composition of fatty acids affected adipose inflammatory responses induced by an HFD. Mice were fed a stearic acid (C18:0)-rich HFD (HFD-S) or a linoleic acid (C18:2)-rich HFD (HFD-L). HFD-L-fed mice showed significant obesity compared with HFD-S-fed mice. Visceral and subcutaneous fat pads were enlarged and contained more NK1.1⁺KLRG1⁺ cells, indicating that G1-ILCs were activated in HFD-L-fed mice. We examined early changes in adipose tissues during the first week of HFD intake, and found that mice fed HFD-L showed increased levels of NK1.1⁺CD11b⁺KLRG1⁺ cells in adipose tissues. In adipose tissue culture, addition of 4-hydroxynonenal, the most frequent product of lipid peroxidation derived from unsaturated fatty acids, induced NK1.1⁺CD11b⁺CD27⁻ cells. We found that calreticulin, a ligand for the NK activating receptor, was induced on the surface of adipocytes after exposure to 4-hydroxynonenal or a 1-week feeding with HFD-L. Thus, excess fatty acid intake and the activation of G1-ILCs initiate and/or modify adipose inflammation.     

Catecholamine-induced lipolysis in adipose tissue and skeletal muscle in obesity

Increased fat storage in adipose and non-adipose tissue (e.g. skeletal muscle) characterizes the obese insulin resistant state. Disturbances in pathways of lipolysis may play a role in the development and maintenance of these increased fat stores. A reduced catecholamine-induced lipolysis may contribute to the development and maintenance of increased adipose tissue stores. To data, a reduced hormone-sensitive lipase (HSL) expression is the best characterized defect contributing to this catecholamine resistance. The recently discovered adipose triglyceride lipase (ATGL) seems not to be involved in the catecholamine resistance of lipolysis observed in abdominal subcutaneous adipose tissue of obese subjects, which contrasts with findings in mice studies. So far, little is known on the regulation of skeletal muscle lipolysis. There is evidence of both HSL and ATGL activity and/or expression in skeletal muscle. A blunted fasting and/or catecholamine-induced lipolysis has been reported in skeletal muscle, but data require confirmation. It is tempting to speculate that an imbalance between ATGL and HSL expression results in incomplete lipolysis and increased accumulation of lipid intermediates in skeletal muscle of obese insulin resistant subjects. The latter may inhibit insulin signalling and play a role in the development of type 2 diabetes. This review summarizes the current knowledge on (intracellular) adipose tissue and skeletal muscle lipolysis in obesity, discusses the underlying mechanisms of these disturbances and will finally address the question whether disturbances in the lipolytic pathways may be primary factors in the etiology of obesity or adaptational responses to the obese insulin resistant state.     

Age-related changes in liver and adipose tissue pyruvate dehydrogenase of genetically obese mice

Changes of the pyruvate dehydrogenase complex in liver and epididymal fat pad were examined longitudinally in obese mice (C57BL/6J-ob/ob) and their lean controls as a function of age. Total pyruvate dehydrogenase in liver was expressed on several reference bases because of differences in hepatic cellularity and protein content between obese mice and their age-matched lean controls. When total hepatic pyruvate dehydrogenase was expressed on a protein basis, the enzyme activity was elevated in obese mice older than 28 weeks in age when compared to lean controls of a similar age. However, when expressed on a DNA basis, total pyruvate dehydrogenase activity in livers of obese mice up to 10 weeks in age was increased when compared to the age-matched lean control. The proportion of hepatic pyruvate dehydrogenase in the active form was also augmented significantly in obese mice from 5 to 28 weeks of age. In 18-week-old obese mice, the proportion of total pyruvate dehydrogenase in the active form of adipose tissue was significantly higher than that of the lean controls. When expressed on a DNA basis, total pyruvate dehydrogenase in the fat pad was also increased in obese mice up to 10 weeks in age when compared to age-matched controls. Total pyruvate dehydrogenase activity in the epididymal fat pad was higher in obese mice than the lean controls in animals as old as 32 weeks in age when the enzyme activity was expressed per 100 g body weight. The increase in the active form and total activity of pyruvate dehydrogenase in both liver and epididymal fat pad during the dynamic early phase of obesity would augment the capacity for acetyl-coenzyme A formation necessary in the support of an accelerated lipogenesis and fat deposition.     

Adipose tissue development: The role of precursor cells and adipogenic factors

Summary Obesity is regarded as a heterogeneous syndrome, which may appear in different forms. Various causes have been found to contribute to its pathogenesis. During recent years investigations of adipose tissue cellularity and its dynamic changes have gained growing interest. An important progress was the discovery of adipose tissue precursor cells. These cells have not yet been precisely identified by morphological and biochemical methods in intact tissue. However, due to methodological developments such precursor cells can be cultured both as primary cultures and as established cell lines. These culture systems have proven to be valuable models for the study of the processes involved in the formation of new fat cells.Abbreviations cAMP Cyclic adenosine monophosphate - cDNA Complementary desoxyribonucleic acid - DHAP Dihydroxy-acetone phosphate - GPDH Glycero-3-phosphate dehydrogenase - IGF-I Insulin-like growth factor I - MIX 1-Methyl-3-isobutylxanthine - mRNA Messenger ribonucleic acid - TNF Tumor necrosis factor Experiments carried out in the authors' laboratories and published in this review were supported by the Deutsche Forschungsgemeinschaft, Sonderforschungsbereich 43 Terms: A number of terms have been used to describe the process of adipocyte development. These are defined as follows [11]:Adipoblast: the pluripotent mesenchymal stem cell of the adipose tissue, which at present is still putative and has not been identified biochemically and morphologicallyPreadipocyte: the cell already committed or determined to become a fat cell with the ability to synthesize lipogenic enzymes and to store lipids; these cells may even contain small lipid droplets or become quickly filled with triglyceridesAdipocyte precursor cells: a precise distinction between adipoblast and preadipocyte is usually not possible and therefore this term is frequently used to describe both differentiation phases, particularly in primary cultureAdipocyte: a cell with a central large lipid vacuole, showing the characteristic signet-ring form, with high activities for enzymes of triglyceride synthesis and releaseDetermination or commitment: the irreversible recruitment of the pluripotent stem cell to a preadipocyte, which may be preceded by one or more cell divisionsAdipogenic conversion: the development of a preadipocyte to the morphological and biochemical appearance of an adipocyte by the expression of a genetic programAdipogenic (adipose) differentiation: the continuous gradual development of an adipoblast to a mature fat cell     

脂肪干细胞在软骨组织工程中的应用

软骨是最早应用组织工程技术成功构建的组织之一,但由于缺乏合适的软骨构建种子细胞,因此其发展相对落后。随着干细胞研究的兴起,脂肪干细胞（ASC）因其具有分布广泛、可利用细胞量大、取材容易等优点,为ASC作为种子细胞应用于组织工程研究提供了可能;但是ASC构建软骨组织的效果却不如骨髓间充质干细胞（BMSC）理想。因此ASC在软骨组织工程中的应用仍面临着诸多问题与挑战,其中最核心的问题是如何提高ASC成软骨的效率。为此从如何纯化脂肪来源细胞、尽可能保持其中干细胞的生物学特性并优化软骨诱导方案3个方面予以综述,为提高ASC成软骨的效率提供参考。     

Functional endothelial progenitor cells derived from adipose tissue show beneficial effect on cell therapy of traumatic brain injury

Endothelial progenitor cells (EPCs) are responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Adipose tissue (AT) is an abundant source of mesenchymal stem cells (MSCs), which have multipotent differentiation ability. We successfully derived EPCs from AT, which maintained a strong proliferative capacity and demonstrated the characteristic endothelial function of uptaking of acetylated low-density lipoprotein. They formed tube-like structures in vitro. Endothelial nitric oxide synthase (eNOS) gene expression in EPCs was similar to that in mature endothelial cells. Transplantation of EPCs derived from AT after the acute phase was applied in rats with traumatic brain injury (TBI). Transplanted EPCs participated in the neovascularization of injured brain. Improving functional recovery, reducement of deficiency volume of brain, host astrogliosis and inflammation were found. These results suggest that adult AT derived stem cells can be induced to functional EPCs and have beneficial effect on cell therapy.     

Regulation of metabolic health and adipose tissue function by group 2 innate lymphoid cells

Adipose tissue (AT) is home to an abundance of immune cells. With chronic obesity, inflammatory immune cells accumulate and promote insulin resistance and the progression to type 2 diabetes mellitus. In contrast, recent studies have highlighted the regulation and function of immune cells in lean, healthy AT, including those associated with type 2 or “allergic” immunity. Although traditionally activated by infection with multicellular helminthes, AT type 2 immunity is active independently of infection, and promotes tissue homeostasis, AT “browning,” and systemic insulin sensitivity, protecting against obesity‐induced metabolic dysfunction and type 2 diabetes mellitus. In particular, group 2 innate lymphoid cells (ILC2s) are integral regulators of AT type 2 immunity, producing the cytokines interleukin‐5 and IL‐13, promoting eosinophils and alternatively activated macrophages, and cooperating with and promoting AT regulatory T (Treg) cells. In this review, we focus on the recent developments in our understanding of group 2 innate lymphoid cell cells and type 2 immunity in AT metabolism and homeostasis.