年龄、饮食及PPARγ对内脏脂肪组织调节性T细胞转录组的影响

<正>炎症是肥胖和2型糖尿病之间的关键联系,过量的能量摄入可诱导内脏脂肪组织(visceral adipose tissue,VAT)的慢性炎症反应,最终引起血脂异常、胰岛素抵抗等代谢异常,甚至发展为2型糖尿病等代谢性疾病。前期研究发现,正常体重小鼠VAT中存在一类调节性T细胞(regulatory T cell,Tregcell),参与调控局部及系统性的炎症和代谢,其转录组与淋巴组织来源     

心外膜脂肪组织与心血管疾病的研究进展

心外膜脂肪组织(epicardial adipose tissue,EAT)是一种特殊的具有局部和全身效应的多功能脂肪组织,其解剖位置特殊,代谢和组织学特征明显区别于其他脂肪组织.在生理条件下,EAT具有产热和保护心脏的作用;而在病理状态下,EAT通过分泌多种促炎细胞因子/脂肪因子,参与心血管疾病(cardiovascular disease,CVD)的发生发展.EAT的厚度/体积及其引发的慢性炎症反应与CVD的严重程度呈显著正相关,运动、减轻体重和药物等均可恢复EAT对心血管的保护作用,提示其有望成为CVD诊断、治疗和预后评价的指标.本文通过对EAT的特征、功能、调节机制以及在血管损伤后重构、动脉粥样硬化、高血压病、心律失常、心功能不全等CVD中的作用做一综述,以期为CVD的防治提供新靶点.     

Irisin:新的运动因子?

运动因子是在运动过程中由骨骼肌产生并分泌到血液循环中的物质,是骨骼肌与运动器官之间的"桥梁"。鸢尾素(Irisin)是过氧化物酶体增殖物激活受体γ辅激活因子(PGC-1α)依赖性肌肉因子,其主要生理功能包括促进白色脂肪组织(white adipose tissue,WAT)向棕色脂肪组织(brown adipose tissue,BAT)转变、改善胰岛素敏感性、参与骨代谢,加速成熟成骨细胞向骨髓基质细胞的转化以及改善大脑功能等。研究表明,在上述领域中,运动干预会引起Irisin表达发生变化。本文将深入讨论Irisin是否符合运动因子的判断标准,并总结不同模式的运动干预对Irisin表达的影响,以便为Irisin与运动因子之间的关系提供新的视角。     

年龄、饮食及PPARγ对内脏脂肪组织调节性T细胞转录组的影响北大核心CSCD

炎症是肥胖和2型糖尿病之间的关键联系,过量的能量摄入可诱导内脏脂肪组织（visceral adipose tissue,VAT）的慢性炎症反应,最终引起血脂异常、胰岛素抵抗等代谢异常,甚至发展为2型糖尿病等代谢性疾病。前期研究发现,正常体重小鼠VAT 中存在一类调节性 T 细胞（regulatory T cell,Treg cell）,参与调控局部及系统性的炎症和代谢,其转录组与淋巴组织来源Treg细胞截然不同。然而,在不同生理或病理条件下,VAT Treg细胞的变化及调控机制尚不清楚。     

年龄、饮食及 PPARγ对内脏脂肪组织调节性 T 细胞转录组的影响

炎症是肥胖和2型糖尿病之间的关键联系,过量的能量摄入可诱导内脏脂肪组织(visceral adipose tissue,VAT)的慢性炎症反应,最终引起血脂异常、胰岛素抵抗等代谢异常,甚至发展为2型糖尿病等代谢性疾病。前期研究发现,正常体重小鼠VAT中存在一类调节性T细胞(regulatory T cell,Tregcell),参与调控局部及系统性的炎症和代谢,其转录组与淋巴组织来源Treg细胞截然不同。然而,在不同生理或病理条件下,VAT Treg细胞的变化及调控机制尚不清楚。美国哈佛大学免疫学系Diane Mathis的团队近期发现:小鼠VAT型Treg细胞的数量及转录组随年龄和肥胖的发生而变     

血管外周脂肪与血管稳态失衡

血管外周脂肪(perivascular adipose tissue, PVAT)是贴近血管外膜的脂肪组织,是活跃的旁自分泌器官,能够分泌多种活性物质,由外而内地影响着血管的稳态。PVAT是一种起源于独特前体细胞的脂肪组织,它兼具白色和棕色脂肪组织样特征。生理状态下,PVAT具有产热能力,并发挥机械保护和血管扩张的作用。病理状态下,比如肥胖、糖尿病、高脂血症、高血压和衰老等,PVAT表型改变和功能失调,表现为脂肪组织扩张、棕色脂肪“白色化”、脂肪细胞中脂质的异常积累和脂肪因子的异常分泌等。近年研究显示,PVAT表型的改变参与了血管重塑、动脉粥样硬化、腹主动脉瘤和高血压等多种病理过程或疾病的发生发展。     

冷刺激对小鼠脂肪组织褐色化和脂代谢的影响

目的:探讨4摄氏度冷刺激对小鼠脂肪组织褐色化的影响。方法:野生型小鼠在4摄氏度环境下饲养一周,称取小鼠重量并取不同的脂肪组织固定,进行HE染色;对血液中甘油三酯、脂肪酸的水平进行检测;检测不同脂肪组织中脂肪含量和相关蛋白的表达水平。结果:野生型小鼠在4℃环境下饲养一周后体重明显降低。血液中甘油三酯、脂肪酸和甘油的水平明显下降。皮下白色脂肪组织(subcutaneous white adipose tissue, SWAT),腹腔生殖腺旁白色脂肪(gonadal visceral white adipose tissue, GWAT)和褐色脂肪(brown adipose tissue, BAT)中的脂肪含量明显降低,其中SWAT和BAT中脂肪含量降低近50%。SWAT发生明显的褐色化现象,组织中出现含有多个脂滴的脂肪细胞,同时褐色化的标志蛋白UCP1(uncoupling protein 1)和Cidea明显增加。GWAT中脂滴仍呈现单室大脂滴,脂肪细胞变小,脂肪积累降低约14%,低于SWAT和BAT中的相应变化。BAT组织中脂滴明显变小,UCP1的表达明显增加。同时我们在三种脂肪组织中都观察到线粒体相关蛋白CPT1 (Carnitine palmitoyltransferase I)的明显增加。结论:冷刺激能明显改变小鼠的脂代谢状态,全身的脂肪积累明显降低。SWAT发生明显的褐色化现象,Cidea和UCP1的表达明显增加。SWAT, GWAT和BAT脂肪组织中有明显的线粒体活性的增加。     

心外膜脂肪组织与心房颤动的分子机制研究进展

心房颤动(atrial fibrillation,AF)是临床上常见的心律失常,与心血管疾病的发病率和死亡率增加相关.心外膜脂肪组织(epicardial adipose tissue,EAT)是具有重要内分泌功能的生物活性器官.近年来已有大量的研究显示EAT的体积、厚度与AF的发生、严重程度及复发相关,但EAT在AF发病机理中的确切作用尚需进一步阐明,为通过干预EAT来治疗AF提供新思路.     

肥胖状态下脂肪组织线粒体功能紊乱与运动调控

线粒体在包括脂肪组织在内的新陈代谢器官中扮演重要角色。脂肪组织包括白色脂肪组织(white adipose tissue, WAT)和棕色脂肪组织(brown adipose tissue, BAT),这两种组织功能相反。白色脂肪组织储存多余的能量,棕色脂肪组织则通过线粒体进行非颤栗性产热来消耗能量。在受到寒冷时、β-肾上腺素能受体激动剂或运动刺激时,白色脂肪组织棕色化形成形态与功能类似棕色脂肪细胞的米色脂肪细胞。在脂肪细胞中,线粒体调节脂肪细胞分化、脂质稳态、支链氨基酸代谢、产热作用以及白色脂肪组织棕色化,因此高活性的线粒体对于脂肪细胞的功能至关重要。研究表明,脂肪组织线粒体功能障碍与肥胖和2型糖尿病等代谢性疾病高度相关。肥胖时线粒体功能紊乱,表现为线粒体生物合成和活性降低、活性氧产生过量以及自噬增加,从而对脂肪组织功能产生不利影响。因此,调节脂肪组织线粒体功能的干预措施将有助于治疗肥胖。研究发现,运动是预防和改善肥胖的重要方法,通过增加线粒体生物合成和活性,改善脂肪组织氧化应激并抑制自噬,从而促进机体代谢。本文深入探讨了脂肪组织线粒体的功能、线粒体紊乱的表现形式以及运动的调控效应,将加深对运动减肥的理解与认识,同时为肥胖症的治疗提供新的方向和思路。     

Obesity and weight loss could alter the properties of adipose stem cells?

The discovery that adipose tissue represents an interesting source of multipotent stem cells has led to many studies exploring the clinical potential of these cells in cell-based therapies. Recent advances in understanding the secretory capacity of adipose tissue and the role of adipokines in the development of obesity and associated disorders have added a new dimension to the study of adipose tissue biology in normal and diseased states. Subcutaneous adipose tissue forms the interface between the clinical application of regenerative medicine and the establishment of the pathological condition of obesity. These two facets of adipose tissue should be understood as potentially related phenomena. Because of the functional characteristics of adipose stem cells, these cells represent a fundamental tool for understanding how these two facets are interconnected and could be important for therapeutic applications. In fact, adipose tissue stem cells have multiple functions in obesity related to adipogenic, angiogenic and secretory capacities. In addition, we have also previously described a predominance of larger blood vessels and an adipogenic memory in the subcutaneous adipose tissue after massive weight loss subsequent to bariatric surgery(ex-obese patients). Understanding the reversibility of the behavior of adipose stem cells in obeses and in weight loss is relevant to both physiological studies and the potential use of these cells in regenerative medicine.     

人体内褐色脂肪组织及其生理功能

褐色脂肪组织(brown adipose tissue,BAT)在小型哺乳动物的非颤抖性产热、体温调节以及体重维持等方面都具有重要的生理功能.在人类中,曾一度认为褐色脂肪组织只在新生儿中存在,在成人体中不存在或数量甚微而没有生理意义.随着医学科技的发展,2009年采用监测癌症及癌症转移的氟化脱氧葡萄糖正电子发射计算机断层显像技术-X射线断层显像技术(18F-FDG PET-CT)检测到在成年人体内也存在功能性的褐色脂肪组织,此发现颠覆了传统的观念,也为人类对抗肥胖提供了新靶标.本文就褐色脂肪组织在人类体内的存在及其潜在的生理意义进行了概述.     

Green tea catechins prevent obesity through modulation of peroxisome proliferator-activated receptors

Epidemiological evidence and experimental studies suggest that drinking green tea is associated with a lower risk of obesity and related diseases. However, the mechanisms of these effects are not clear. In the present study, we investigated the anti-obesity mechanisms of green tea catechins (GTCs) through modulation of peroxisome proliferator activated-receptor (PPAR) pathways in high-fat diet-induced obesity in rats. GTC supplementation significantly attenuated the increased body and liver weights and the elevated serum and liver triglyceride levels. Meanwhile, GTCs increased the PPARγ levels in subcutaneous white adipose tissue (SWAT) and decreased the PPAR levels in visceral white adipose tissue (VWAT). In addition, GTC treatment up-regulated the levels of PPARδ in SWAT, VWAT, and brown adipose tissue and increased the expression of genes involved in fatty acid oxidation in brown adipose tissue. Our results suggest that GTCs exert their anti-obesity mechanism in part by modulating PPAR signaling pathways.     

人类棕色脂肪组织产热节律调控

正棕色脂肪组织(brown adipose tissue,BAT)可利用葡萄糖和脂肪酸经"非寒战产热"(non-shivering thermogenesis)为机体提供热量;该功能为人类婴儿期的重要热量来源,但却在成年期退化;目前,医学界发现,诱导该功能在人类成年期重现,可能是防治肥胖与其他代谢疾病(如2型糖尿病)的重要治疗靶点;因此,揭示棕色脂肪组织产热调控机制,成为研究热点。最近,澳大利亚新南威尔士大学的Paul Lee等研究人员,首次揭示人类棕色脂肪组织产热存在精密的昼夜调控节律,该成果于2016年4月发表在《Cell Metabolism》。     

小哺乳动物在高寒环境中的生存对策Ⅱ.高原鼠兔和根田鼠非颤抖性产热（NST）的季节性变化

本文对生存在高寒地区的两种非冬眠草食性小哺乳动物--高原鼠兔(Ochotona curzoniae)和根田鼠(Microtus oeconomus)的非颤抖性产热(Nonshlvering thermogenesis,NST)的季节性变化进行了测定,并对NST与褐色脂肪组织(Brown adipose tissue,BAT)的关系进行了分析,同时阐述了高寒环境中非冬眠草食性小哺乳动物的生存对策。     

Cidea controls lipid droplet fusion and lipid storage in brown and white adipose tissue

Excess lipid storage in adipose tissue results in the development of obesity and other metabolic disorders including diabetes,fatty liver and cardiovascular diseases.The lipid droplet(LD)is an important subcellular organelle responsible for lipid storage.We previously observed that Fsp27,a member of the CIDE family proteins,is localized to LD-contact sites and promotes atypical LD fusion and growth.Cidea,a close homolog of Fsp27,is expressed at high levels in brown adipose tissue.However,the exact role of Cidea in promoting LD fusion and lipid storage in adipose tissue remains unknown.Here,we expressed Cidea in Fsp27-knockdown adipocytes and observed that Cidea has similar activity to Fsp27 in promoting lipid storage and LD fusion and growth.Next,we generated Cidea and Fsp27 double-deficient mice and observed that these animals had drastically reduced adipose tissue mass and a strong lean phenotype.In addition,Cidea/Fsp27 double-deficient mice had improved insulin sensitivity and were intolerant to cold.Furthermore,we observed that the brown and white adipose tissues of Cidea/Fsp27double-deficient mice had significantly reduced lipid storage and contained smaller LDs compared to those of Cidea or Fsp27single deficient mice.Overall,these data reveal an important role of Cidea in controlling lipid droplet fusion,lipid storage in brown and white adipose tissue,and the development of obesity.     

A familiar stranger:CD34 expression and putative functions in SVF cells of adipose tissue

Human adipose tissue obtained by liposuction is easily accessible and an abundant potential source of autologous cells for regenerative medicine applications. After digestion of the tissue and removal of differentiated adipocytes, the so-called stromal vascular fraction (SVF) of adipose, a mix of various cell types, is obtained. SVF contains mesenchymal fibroblastic cells, able to adhere to culture plastic and to generate large colonies in vitro , that closely resemble bone marrow-derived colony forming units-fibroblastic, and whose expanded progeny, adipose mesenchymal stem/stromal cells (ASC), show strong similarities with bone marrow mesenchymal stem cells. The sialomucin CD34, which is well known as a hematopoietic stem cell marker, is also expressed by ASC in native adipose tissue but its expression is gradually lost upon standard ASC expansion in vitro . Surprisingly little is known about the functional role of CD34 in the biology and tissue forming capacity of SVF cells and ASC. The present editorial provides a short introduction to the CD34 family of sialomucins and reviews the data from the literature concerning ex- pression and function of these proteins in SVF cells and their in vitro expanded progeny.     

Vaspin与动脉粥样硬化的研究进展

内脏脂肪组织特异性丝氨酸蛋白酶抑制物(Vaspin)是新发现的脂肪因子,主要由内脏脂肪组织产生,它的分泌和表达受多种因素的影响,并与肥胖、2型糖尿病、动脉粥样硬化(Atherosclerosis,As)等有关。Vaspin具有胰岛素增敏性、改善糖耐量、抑制血管炎症反应等作用,对这些作用机制的认识,能为防治动脉粥样硬化提供新的治疗靶点。     

高脂高糖食物诱导中缅树鼩肥胖的研究

为了研究高糖高脂食物诱导中缅树鼩肥胖的模型,在高脂高糖食物诱导条件下进行了中缅树鼩的血液指标测定、脂肪组织流式细胞分析和正电子发射计算机断层显像(positron emission tomography/computed tomography,PET/CT)扫描成像研究。结果表明:在28 d时中缅树鼩白色脂肪组织(white adipose tissue,WAT)质量是对照组的3.7倍,49 d时WAT质量是对照组的6.4倍;49 d时实验组树鼩的甘油三酯(triglyceride,TG)和高密度脂蛋白(high density lipoprotein,HDL)含量与对照组树鼩差异显著,血糖(blood glucose)水平、总胆固醇(total cholesterol,CHOL)和血小板(blood platelet,PLT)含量与对照组树鼩差异极显著;此外,食物诱导28 d组中缅树鼩腹部WAT和褐色脂肪组织(brown adipose tissue,BAT)的18氟-氟化脱氧葡萄糖(18-fluoro-fluorodeoxyglucose,~(18)F-FDG)吸收60 min后,平均辐射值(standardized uptake value,SUV)显著高于对照组,49 d时有所下降。流式细胞分析结果表明,28 d时WAT和BAT中R2群标记阳性显著增加,而49 d后有所降低。以上结果表明:食物诱导可以使中缅树鼩产生肥胖并显著增加中缅树鼩WAT的质量,中缅树鼩在28 d时会出现肥胖抵抗的现象,但是随着时间的延长,该抵抗现象逐渐减少。     

脂肪细胞分泌蛋白质Acrp30及其生理功能

脂肪组织是人体最大的能量储存库,在需要时动用储存的脂肪,向机体供能。脂肪组织同时也是一个极其重要的分泌器官。Acrp30(adipocyte complete related protein 30 kD,)就是由脂肪组织分泌的一种活性蛋白质,参与能量代谢、炎症反应等生理过程,与肥胖、Ⅱ型糖尿病、动脉粥样硬化、心血管疾病等疾病有密切的关系。