脂肪组织血管重塑及其与慢性炎症的相互作用

肥胖机体胰岛素抵抗会引起血管并发症已得到认同,但新近关于肥胖机体慢性炎症的研究发现,在出现胰岛素抵抗前脂肪组织脉管系统已发生功能障碍。本研究分析脂肪组织毛细血管发生变化与缺氧的关系和缺氧与慢性炎症的关系,认为肥胖机体脂肪组织毛细血管发生变化,引起脂肪组织缺氧;缺氧诱导慢性炎症,肥胖关联的炎症又引起脂肪组织血管重塑,加剧脂肪组织功能障碍和胰岛素抵抗;提出在肥胖者体内,脂肪组织血管重塑能够调控慢性炎症和全身胰岛素敏感性。     

营养干预对肥胖、糖尿病机体糖脂代谢和肠道菌群的影响

肥胖、糖尿病都是代谢性疾病,会引起一系列并发症,严重危害人体健康。其病因可能是遗传和环境共同作用的结果,糖脂代谢和肠道菌群是其中的重要环境因素。糖脂代谢紊乱会引起肥胖、糖尿病,不当饮食也会导致患者的糖脂代谢紊乱加剧,通过人为改变糖类、脂肪和蛋白质的配比进行营养干预,可调节自身糖脂代谢水平以达到缓解病症和治疗的目的。此外,肥胖、糖尿病病人的肠道菌群多样性下降且功能紊乱,也是进一步维持和加剧病程的重要原因,而通过营养干预可促进肠道菌群多样性恢复及有益代谢物生成,对病症恢复起到较好作用。综述了肥胖、糖尿病与机体糖脂代谢和肠道菌群的相互作用关系,及营养干预对其的影响。     

茶多酚对脂质代谢具有调节作用

 脂质代谢是维持人体正常功能的三大代谢之一,脂肪代谢紊乱会引起肥胖等病证,导致身心疾病。肥胖事实上已经成为世界范围内的一个重要的健康问题,以脂肪组织增生和脂肪组织肥大为特点。脂肪组织分为白色脂肪组织（WAT）和棕色脂肪组织（BAT）,WAT 负责储存能量,而BAT 负责能量代谢。     

ATGL生化功能调节及与心肌肥厚的关系

脂肪甘油三酯脂肪酶是脂肪分解代谢限速酶,ATGL广泛表达于全身各组织,尤其高表达于脂肪组织、肝脏和心脏等.ATGL敲除显示动物因大量甘油三酯堆积而产生严重肥胖,心脏受累尤其严重.主要介绍ATGL功能调节及其功能失调与心肌肥厚的关系     

RAS与肥胖性高血压

RAS是维持机体血压和电解质平衡的内分泌系统，近年来，研究发现RAS的成分都能在脂肪组织中表达，且ANGII作为脂肪分化与代谢的营养因子。本文分析脂肪组织中血管紧张素原与肥胖和高血压的关联，综述了血管紧张素Ⅱ对脂肪细胞细胞分化代谢的影响及调节机理，探讨RAS对肥胖性高血压形成的影响。分析表明RAS对肥胖性高血压具有一定的诱导作用，且其对肥胖的诱导大都由AT1R介导，同时AT1R和AT2R对肥胖的形成也具有拮抗作用。从而对肥胖性高血压的病理机制的探索以及治疗提供新思路。     

Chemerin、肥胖与运动研究进展

Chemerin主要由脂肪细胞分泌的新型脂肪细胞因子,具有多种生物学功能,在肥胖和胰岛素抵抗中发挥一定生理效应。本文主要从Chemerin与肥胖、胰岛素抵抗、2型糖尿病、炎症的关系及运动对Chemerin的影响进行综述,为肥胖及肥胖相关疾病的运动治疗提供理论依据。     

瘦素与能量平衡

通过对瘦素的研究分析,了解到瘦素受体广泛存在于下丘脑、肺、肾脏、肌肉和脂肪组织等中。瘦素是由ob基因编码、在脂肪组织合成分泌的蛋白质类激素,含有146个氨基酸,主要功能是调控进食、能量及体重。瘦素和其他激素一样,需要与特异的受体结合才能发挥其生物学作用。总之,瘦素的发现,为进一步研究肥胖的发生机制,以及预防和治疗肥胖开辟了一条崭新的途径。     

低能量食品:时代对食品工业提出的新课题

目前，我国的肥胖症患者和隐性肥胖者已达1.5~2亿人。随着社会的发展，能量摄入过剩的现象将日趋严重。能量是指身体由食物中获得的需要用作“燃料”的能量，当人体的能量摄入大于消耗时，超出的部分就会以脂肪形式贮存于机体中，使得脂肪组织增多，形成肥胖。长期肥胖易发生糖尿病、高血压、冠心病、中风、肾脏病、脂肪肝与胆囊疾病。因此，肥胖已逐渐成为危害我国人民健康的一种重要疾病。减肥就是要限制能量的摄入，增加其消耗，或两者兼而有之。低能量食品的研究和开发就是为适应这种需要产生的，这不仅仅是一种时尚，更重要的是体现了…     

Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver

The earliest defect in developing type 2 diabetes is insulin resistance, characterized by decreased glucose transport and metabolism in muscle and adipocytes. The glucose transporter GLUT4 mediates insulin-stimulated glucose uptake in adipocytes and muscle by rapidly moving from intracellular storage sites to the plasma membrane. In insulin-resistant states such as obesity and type 2 diabetes, GLUT4 expression is decreased in adipose tissue but preserved in muscle. Because skeletal muscle is the main site of insulin-stimulated glucose uptake, the role of adipose tissue GLUT4 downregulation in the pathogenesis of insulin resistance and diabetes is unclear. To determine the role of adipose GLUT4 in glucose homeostasis, we used Cre/loxP DNA recombination to generate mice with adipose-selective reduction of GLUT4 (G4A-/-). Here we show that these mice have normal growth and adipose mass despite markedly impaired insulin-stimulated glucose uptake in adipocytes. Although GLUT4 expression is preserved in muscle, these mice develop insulin resistance in muscle and liver, manifested by decreased biological responses and impaired activation of phosphoinositide-3-OH kinase. G4A-/- mice develop glucose intolerance and hyperinsulinaemia. Thus, downregulation of GLUT4 and glucose transport selectively in adipose tissue can cause insulin resistance and thereby increase the risk of developing diabetes.     

Mechanisms linking obesity to insulin resistance and type 2 diabetes

Obesity is associated with an increased risk of developing insulin resistance and type 2 diabetes. In obese individuals, adipose tissue releases increased amounts of non-esterified fatty acids, glycerol, hormones, pro-inflammatory cytokines and other factors that are involved in the development of insulin resistance. When insulin resistance is accompanied by dysfunction of pancreatic islet beta-cells - the cells that release insulin - failure to control blood glucose levels results. Abnormalities in beta-cell function are therefore critical in defining the risk and development of type 2 diabetes. This knowledge is fostering exploration of the molecular and genetic basis of the disease and new approaches to its treatment and prevention.     

Adipocytes as regulators of energy balance and glucose homeostasis

Adipocytes have been studied with increasing intensity as a result of the emergence of obesity as a serious public health problem and the realization that adipose tissue serves as an integrator of various physiological pathways. In particular, their role in calorie storage makes adipocytes well suited to the regulation of energy balance. Adipose tissue also serves as a crucial integrator of glucose homeostasis. Knowledge of adipocyte biology is therefore crucial for understanding the pathophysiological basis of obesity and metabolic diseases such as type 2 diabetes. Furthermore, the rational manipulation of adipose physiology is a promising avenue for therapy of these conditions.     

Macrophage-specific PPARgamma controls alternative activation and improves insulin resistance

Obesity and insulin resistance, the cardinal features of metabolic syndrome, are closely associated with a state of low-grade inflammation. In adipose tissue chronic overnutrition leads to macrophage infiltration, resulting in local inflammation that potentiates insulin resistance. For instance, transgenic expression of Mcp1 (also known as chemokine ligand 2, Ccl2) in adipose tissue increases macrophage infiltration, inflammation and insulin resistance. Conversely, disruption of Mcp1 or its receptor Ccr2 impairs migration of macrophages into adipose tissue, thereby lowering adipose tissue inflammation and improving insulin sensitivity. These findings together suggest a correlation between macrophage content in adipose tissue and insulin resistance. However, resident macrophages in tissues display tremendous heterogeneity in their activities and functions, primarily reflecting their local metabolic and immune microenvironment. While Mcp1 directs recruitment of pro-inflammatory classically activated macrophages to sites of tissue damage, resident macrophages, such as those present in the adipose tissue of lean mice, display the alternatively activated phenotype. Despite their higher capacity to repair tissue, the precise role of alternatively activated macrophages in obesity-induced insulin resistance remains unknown. Using mice with macrophage-specific deletion of the peroxisome proliferator activated receptor-gamma (PPARgamma), we show here that PPARgamma is required for maturation of alternatively activated macrophages. Disruption of PPARgamma in myeloid cells impairs alternative macrophage activation, and predisposes these animals to development of diet-induced obesity, insulin resistance, and glucose intolerance. Furthermore, gene expression profiling revealed that downregulation of oxidative phosphorylation gene expression in skeletal muscle and liver leads to decreased insulin sensitivity in these tissues. Together, our findings suggest that resident alternatively activated macrophages have a beneficial role in regulating nutrient homeostasis and suggest that macrophage polarization towards the alternative state might be a useful strategy for treating type 2 diabetes.     

PPAR-γ is a major driver of the accumulation and phenotype of adipose tissue Treg cells

Obesity and type-2 diabetes have increased markedly over the past few decades, in parallel. One of the major links between these two disorders is chronic, low-grade inflammation. Prolonged nutrient excess promotes the accumulation and activation of leukocytes in visceral adipose tissue (VAT) and ultimately other tissues, leading to metabolic abnormalities such as insulin resistance, type-2 diabetes and fatty-liver disease. Although invasion of VAT by pro-inflammatory macrophages is considered to be a key event driving adipose-tissue inflammation and insulin resistance, little is known about the roles of other immune system cell types in these processes. A unique population of VAT-resident regulatory T (Treg) cells was recently implicated in control of the inflammatory state of adipose tissue and, thereby, insulin sensitivity. Here we identify peroxisome proliferator-activated receptor (PPAR)-γ, the 'master regulator' of adipocyte differentiation, as a crucial molecular orchestrator of VAT Treg cell accumulation, phenotype and function. Unexpectedly, PPAR-γ expression by VAT Treg cells was necessary for complete restoration of insulin sensitivity in obese mice by the thiazolidinedione drug pioglitazone. These findings suggest a previously unknown cellular mechanism for this important class of thiazolidinedione drugs, and provide proof-of-principle that discrete populations of Treg cells with unique functions can be precisely targeted to therapeutic ends.     

肥胖／糖尿病过程中大鼠不同部位脂肪细胞大小的比较

为比较大鼠肥胖／糖尿病过程中脂肪分布及脂肪细胞大小的变化,初步阐明脂肪细胞大小与2型糖尿病发生相关性。将Wistar雄性大鼠随机分为3组,每组12只：普通饮食组（正常对照）,高脂饮食组（肥胖）,高脂饮食＋链脲佐菌素组（糖尿病组）。第0周随机抽取6只大鼠处死后,取皮下脂肪及腹膜内脂肪,用2．5％甲醛乙醇溶液固定,进行石蜡包埋,HE染色,制成切片。在400倍光学显微镜下随机选取10个视野检测统计脂肪细胞数量及面积大小（mm^2）。在饲养过程中分别选取第6、9、12、14周等4个时间点,每个时间点各组随机处死2只大鼠,取皮下脂肪及腹膜内脂肪进行相同处理。同时,在各个时间点对大鼠体重、血糖进行检测。各组大鼠皮下脂肪细胞与腹膜内脂肪细胞大小差异均有统计学意义（F=9．653,P=0．001;F=160．605,P=0．000）,其中正常组与肥胖组、正常组与糖尿病组差异都有统计学意义,而肥胖组与糖尿病组差异无统计学意义。不同部位脂肪细胞大小的差异无统计学意义。脂肪细胞的体积增大,与大鼠体重及血糖变化相平行。大鼠脂肪细胞的体积增大与肥胖／糖尿病的演进过程相平行,大鼠脂肪组织的分布与脂肪细胞的大小无明显相关性。     

褐色脂肪组织中的解偶联蛋白

褐色脂肪组织的调节产热等方面的功能近年来一直倍受关注,尤其是存在其中的解偶联蛋白更是近年来研究的热点,本文概述了解偶联蛋白及其基因的结构、解偶联蛋白的生理作用。     

辣椒碱调节机体糖脂代谢的机理研究

辣椒碱是辣椒中含有的一类具有辛辣刺激口感的生物碱,主要成分是辣椒素和二氢辣椒素。许多研究表明辣椒碱具有镇痛、抗癌、减肥、降糖、降脂和抗炎症的作用。血脂血糖代谢异常是导致肥胖、高脂血症和糖尿病的主要因素之一,辣椒碱在动物和人体实验中均表现出良好的控糖、降脂、减肥功效,其作用效果和作用机理引起广泛关注。综述了辣椒碱在调节机体糖脂代谢方面的作用效果,以及辣椒碱作用辣椒素受体TRPV1通道、膳食糖脂的消化吸收、肠道菌群组成以及肝脏、胰腺、脂肪组织、神经系统中与糖脂代谢相关酶、基因调控糖脂代谢的可能机理,以期为辣椒碱的深度开发利用和科学消费提供参考。