蛋白质组学在胰岛素抵抗研究中的应用

胰岛素抵抗（insulin resistance,IR）即指一定量的胰岛素与其特异性受体结合后所产生的生物效应低于正常。表现为外周组织尤其是肌肉、脂肪组织对葡萄糖摄取减少及胰岛素抑制肝葡萄糖输出的作用减弱．是肥胖、高血压、糖尿病及动脉粥样硬化等多种疾病的共同危险因素和基础。蛋白质组学技术的不断发展和完善,为真正了解胰岛素抵抗发生发展规律提供了可能,该文介绍蛋白质组学在胰岛素抵抗发生机制、标志物的寻找及治疗胰岛素抵抗新药开发中的应用．     

蛋白质组学在肥胖症研究中的应用

在世界范围内,肥胖及其相关代谢性疾病的发生率逐年增加,尤其是儿童肥胖症的普遍存在引起了广泛关注。过度肥胖是2型糖尿病、心血管疾病和一些肿瘤的重要危险因素。有关肥胖症的研究过去主要集中在脂肪组织功能改变,脂肪细胞分化,棕色脂肪转化,线粒体功能失调,以及肠道营养物质吸收这些方面的分子生物学研究。肥胖作为一种复杂的代谢紊乱性疾病,基因层面的探索并不能全面体现肥胖的机体内各种参与能量代谢的蛋白质功能的变化。高通量蛋白质组学的应用为研究肥胖的机体蛋白质表达和功能变化提供了可能,并为进一步理解肥胖症的发病机理,寻找疾病相关干预靶点提供了重要的帮助。本综述,总结了近年来关于蛋白质组学在肥胖症病理生理变化中的相关研究,并讨论参与肥胖症发生的可能机制和干预作用靶点。     

褐色脂肪组织研究的最新进展和科学意义

哺乳动物体内存在着褐色脂肪组织。有别于白色脂肪组织储存能量的功能,褐色脂肪组织的主要功能是通过产热作用来维持机体的能量代谢平衡。陆续有研究阐明调控褐色脂肪组织分化与能量代谢过程的分子机制,逐渐揭示了褐色脂肪组织分化与能量代谢过程中涉及的信号通路与转录调控。这不仅让我们更好地理解褐色脂肪组织在能量代谢调控中的重要作用,而且为基于褐色脂肪组织的肥胖治疗提供了理论依据。本文阐述了近年来研究发现的褐色脂肪组织分化与代谢过程中发挥重要作用的信号通路与转录调控,并讨论了多种基于针对褐色脂肪组织的肥胖治疗手段的有效性与可行性。     

乳腺脂肪组织调节乳腺发育的研究进展

乳腺是哺乳动物哺育子代的重要器官,其通过分泌乳汁给子代提供充足的营养物质,乳腺的健康发育对泌乳以及提高子代的存活率具有重要意义.脂肪组织是乳腺重要的组成部分,在乳腺发育和循环重构过程中,乳腺脂肪组织随之呈现规律性的形态和功能变化,乳腺脂肪组织的动态变化是乳腺循环性发育重构的重要特征.脂肪组织能够分泌特殊的"脂肪因子"调节上皮细胞的功能和乳腺的发育,并且存在与上皮细胞相互转换的潜能.本综述综合近年来乳腺脂肪组织的相关研究进展,为后续研究脂肪组织调节乳腺发育的机制提供基础数据.     

定量蛋白质组学在急性高原病研究中的应用进展

急性高原病(acute mountain sickness,AMS)是人体急性暴露于高原低压低氧环境后出现多系统生理紊乱的临床综合征。定量蛋白质组学技术可以系统定量并描述机体蛋白质组成和动态变化规律,近年来在多种疾病的预防、诊断、治疗和发生机制等方面研究应用广泛。本文系统综述了定量蛋白质组学技术及其在AMS的预防、诊断、治疗和急进高原习服机制研究中的应用进展,以期为AMS的发病机制、提前干预、临床治疗和AMS的蛋白质组学研究提供参考。     

脂肪分泌组学的研究进展

分泌蛋白是由细胞主动运输到细胞外的一大类具有重要生物学功能的蛋白,主要参与细胞信号转导、细胞的增殖、分化及凋亡等多种生物学过程.细胞、组织、器官及个体分泌的所有蛋白称为分泌组.脂肪组织曾被认为只是机体内能量储藏的地方,但现在发现它还是体内最大的内分泌器官.近年来,由于蛋白质组学技术的快速发展,脂肪分泌组研究已成为脂肪生...     

肥大细胞在脂肪组织中的作用

肥大细胞(mast cells)起源于骨髓造血干细胞，定植到机体各个外周组织后继续发育成熟，在过敏性反应和预防微生物感染等方面发挥重要作用。近来研究发现，肥胖患者的脂肪组织含有大量肥大细胞，引发人们对脂肪组织中肥大细胞作用的关注。肥大细胞可释放出多种生物活性介质，作用于脂肪组织，影响脂肪组织中细胞外基质的重塑和各种炎性细胞的活动。更多研究还表明肥大细胞可能参与到肥胖、糖尿病等代谢性疾病的发病机理，影响疾病的进展。本文总结近年来对脂肪组织中肥大细胞研究的一系列成果，对肥大细胞在脂肪组织中的生物学作用进行综述。     

组织器官通讯对骨骼肌发育的作用及调控机制研究进展

骨骼肌是动物机体最重要的器官之一,研究骨骼肌发育调控机制对于肌肉相关疾病的诊断以及家畜肉质的改善都有着重要意义。骨骼肌发育调控是一个复杂的过程,受到大量肌肉分泌因子和信号通路的调节。此外,为了维持体内代谢稳态并最大限度地利用能量,机体协调多个组织器官形成了复杂而又精密的代谢调控网络,对于调控骨骼肌发育也发挥着重要的作用。随着组学技术的发展,人们对于组织器官通讯的潜在机制进行了深入研究。本文综述了脂肪组织、神经组织、肠道等组织器官通讯对于骨骼肌发育的影响,以期为靶向调控骨骼肌发育提供理论基础。     

脂肪细胞的起源

脂肪组织是机体内最重要的能量储存器官,具有产热、维持体温、内分泌和支持填充等多种功能,脂肪的功能异常被证实与2型糖尿病、高血压、动脉粥样硬化和肿瘤等多种疾病相关。一般认为在发育过程中脂肪细胞起源于中胚层,但近年来也有研究发现部分脂肪细胞起源于外胚层神经嵴。在发育完成后,机体内仍存在前脂肪细胞,在适当的条件下可继续分化为脂肪细胞,这些前脂肪细胞与血管有着密切的联系,但其在体分布及起源则有待证明。近年来对前脂肪细胞分化为脂肪细胞的终末分化过程研究较多,然而脂肪细胞的起源,以及间充质干细胞向前脂肪细胞的定向分化过程却仍不清楚。本文总结了近年来该领域的一系列研究成果,对脂肪细胞的起源问题进行综述。     

肉用牛、绵羊脂肪组织特性、发育规律及其评鉴方法

脂肪组织是动物的主要能量储存器官,同时也是重要的内分泌器官,能够调控机体能量稳态.对于反刍家畜而言,脂肪组织关系到御寒能力、免疫力、繁殖力、肉品质、饲料转化效率等多个生存与生产相关的重要性状.动物脂肪组织储存于皮下、内脏、肌间、肌内和骨骼等5个主要部位.依据脂肪细胞的类型又可以分为白色脂肪组织和褐色脂肪组织两大类.目前针对肉用牛、绵羊白色脂肪组织的发育规律方面的研究较为全面,而褐色脂肪组织的研究相对较少.针对反刍动物皮下、肌内等部位脂肪已建立了生产评价体系,但尚无针对褐色脂肪的评价标准.本文从动物健康与生产实际两个方面出发,分析了肉用牛、绵羊脂肪组织特性、发育规律及其鉴定与评价方法.     

Adipose tissue development--impact of the early life environment

Increasing experimental and observational evidence in both animals and humans suggests that early life events are important in setting later fat mass. This includes both the number of adipocytes and the relative distribution of both brown and white adipose tissue. Brown adipose tissue is characterised as possessing a unique uncoupling protein (UCP)1 which enables the rapid generation of large amounts of heat and is most abundant in the newborn. In large mammals such as sheep and humans, brown fat that is located around the major internal organs, is largely lost during the postnatal period. However, it is retained in small and discrete areas into adulthood when it is sensitive to environmental cues such as changes in ambient temperature or day length. The extent to which brown adipose tissue is lost or replaced by white adipose tissue and/or undergoes a process of transdifferentiation remains controversial. Small amounts of UCP1 can also be present in skeletal muscle which now appears to share the same common precursor cell as brown adipose tissue. The functional consequences of UCP1 in muscle remain to be confirmed but it could contribute to dietary induced thermogenesis. Challenges in elucidating the primary mechanisms regulating adipose tissue development include changes in methylation status of key genes during development in different species, strains and adipose depots. A greater understanding of the mechanisms by which early life events regulate adipose tissue distribution in young offspring are likely to provide important insights for novel interventions that may prevent excess adiposity in later life.     

DNA甲基化与脂肪组织生长发育

DNA甲基化作为一种重要的表观遗传学修饰方式,在维持正常细胞功能、遗传印记、胚胎发育以及人类肿瘤发生中起着重要作用。DNA甲基化最重要的作用是调控基因表达,它是细胞调控基因表达的重要表观遗传机制之一。近年来的研究发现,DNA甲基化在脂肪组织生长发育以及肥胖症发生过程中发挥着重要作用。DNA甲基化通过调控脂肪细胞分化转录因子、转录辅助因子以及其他脂肪代谢相关基因的表达,从而调控脂肪组织的生长发育。该文综述了脂肪组织生长发育过程中DNA甲基化的最新研究进展,探讨了脂肪组织DNA甲基化的研究趋势和未来发展方向。     

Friend or foe: Multiple roles of adipose tissue in cancer formation and progression

Obesity is well-known as the second factor for tumorigenesis after smoking and is bound up with the malignant progression of several kinds of cancers, including esophageal cancer, liver cancer, colorectal cancer, kidney cancer, and ovarian cancer. The increased morbidity and mortality of obesity-related cancer are mostly attributed to dysfunctional adipose tissue. The possible mechanisms connecting dysfunctional adipose tissue to high cancer risk mainly focus on chronic inflammation, obesity-related microenvironment, adipokine secretion disorder, and browning of adipose tissue, and so forth. The stromal vascular cells in adipose tissue trigger chronic inflammation through secreting inflammatory factors and promote cancer cell proliferation. Hypertrophic adipose tissues lead to metabolic disorders of adipocytes, such as abnormal levels of adipokines that mediate cancer progression and metastasis. Cancer patients often show adipose tissue browning and cancerous cachexia in an advanced stage, which lead to unsatisfied chemotherapy effect and poor prognosis. However, increasing evidence has shown that adipose tissue may display quite opposite effects in cancer development. Therefore, the interaction between cancers and adipose tissue exert a vital role in mediates adipose tissue dysfunction and further leads to cancer progression. In conclusion, targeting the dysfunction of adipose tissue provides a promising strategy for cancer prevention and therapy.     

Detection of DNA fragmentation and apoptotic proteins, and quantification of uncoupling protein expression by real-time RT-PCR in adipose tissue

Better understanding of the mechanisms involved in adipose tissue growth and metabolism is critical for the development of more effective treatments for obesity. However, because of its high lipid and low protein content, adipose tissue can present unique problems in some experimental procedures. We describe three protocols that provide new or improved methods for analysis of DNA, RNA, and protein from different adipose tissues. The first protocol provides a simple and rapid method for separation of fragmented DNA and visualization of apoptotic DNA laddering without the need for radioisotopes. This technique allows for an estimate of the amount of DNA fragmentation, and hence, apoptosis. The second protocol details subcellular fractionation of adipose tissue for the extraction of protein in the mitochondrial and cytosol fractions and the measurement of apoptotic protein (Bcl-2 and Bax) levels in each fraction. The last protocol involves extraction of total RNA from adipose tissue and the measurement of uncoupling protein mRNA using real-time RT-PCR, a method that has not previously been used to measure expression of uncoupling proteins in adipose tissue.     

Time course of high-fat diet-induced reductions in adipose tissue mitochondrial proteins: potential mechanisms and the relationship to glucose intolerance

Increasing evidence suggests that reduced adipose tissue mitochondrial content is associated with the pathogenesis of type 2 diabetes. These investigations have utilized severely insulin-resistant rodent models. Thus, it is difficult to ascertain the potential mechanisms that initiate these changes and whether reductions in adipose mitochondria are an initiating event in the development of impaired glucose homeostasis. Thus, we sought to determine the time course of high-fat diet-induced reductions of mitochondrial content in epididymal adipose tissue in relation to changes in purported mediators of mitochondrial biogenesis and the development of impaired glucose homeostasis. Male Wistar rats were fed a high-fat diet ( approximately 59% of kcals from fat) for 2, 4, or 6 wk. Six weeks of high-fat feeding resulted in reductions in CORE I, COX IV, cytochrome c, HSP60, relative mtDNA copy number, and PGC-1alpha expression. These changes were not associated with decreases in eNOS and AMPK or increases in markers of oxidative stress. Interestingly, ex vivo treatment of adipose tissue cultures with palmitate led to decreases in PGC-1alpha expression and COX IV and CORE I protein content as observed in vivo. Thus, the high-fat diet-induced reductions in adipose tissue mitochondrial proteins may be mediated by increases in plasma fatty acids. Importantly, reductions in adipose tissue mitochondrial content occurred after the development of impaired glucose homeostasis. Thus, reductions in adipose tissue mitochondrial proteins are most likely not a causal event in the development of impaired glucose homeostasis.     

Bioactive Compounds and Adipocyte Browning Phenomenon

Overweight and obesity have become worldwide health issues in most countries. Current strategies aimed to prevent or reduce overweight and obesity have mainly focused on the genes and molecular mechanisms that give the functional characteristics to different types of adipose tissue. The Browning phenomenon in adipocytes consists of phenotypic and metabolic changes within white adipose tissue (WAT) activated by thermogenic mechanisms similar to that occurring in brown adipose tissue (BAT); this phenomenon has assumed great relevance due to its therapeutic potential against overweight and obesity. In addition, the study of inflammation in the development of overweight and obesity has also been included as a relevant factor, such as the pro-inflammatory mechanisms promoted by M1-type macrophages in adipose tissue. Studies carried out in this area are mainly performed by using the 3T3-L1 pre-adipocyte cell line, testing different bioactive compound sources such as plants and foods; nevertheless, it is necessary to standardize protocols used in vitro as well to properly scale them to animal models and clinical tests in order to have a better understanding of the mechanisms involved in overweight and obesity.     

Thematic review series: adipocyte biology. Adipose tissue function and plasticity orchestrate nutritional adaptation

This review focuses on adipose tissue biology and introduces the concept of adipose tissue plasticity and expandability as key determinants of obesity-associated metabolic dysregulation. This concept is fundamental to our understanding of adipose tissue as a dynamic organ at the center of nutritional adaptation. Here, we summarize the current knowledge of the mechanisms by which adipose tissue can affect peripheral energy homeostasis, particularly in the context of overnutrition. Two mechanisms emerge that provide a molecular understanding for obesity-associated insulin resistance. These are a) the dysregulation of adipose tissue expandability and b) the abnormal production of adipokines. This knowledge has the potential to pave the way for novel therapeutic concepts and strategies for managing and/or correcting complications associated with obesity and the metabolic syndrome.