脂肪组织巨噬细胞研究进展

正肥胖(Obesity)是指体内脂肪储量超标,包括脂肪细胞数量的增加和体积的增大,世界卫生组织对其定义为"超重或肥胖,是可损害健康的异常或过量脂肪累积",肥胖症是以肥胖为特征的异常代谢症群。随着研究的深入,人们发现肥胖症其实是一种由多种因素引起的慢性代谢性疾病,同糖尿病、心血管疾病等多种代谢性疾病的发生发展密切相关,慢性炎症反应在肥胖症中扮演着重要角色~([1])。     

青岛市7至15岁少年儿童高尿酸血症发生率调查

随着我国经济的发展,人民生活水平提高和饮食结构的改变,高尿酸血症的发生率逐年增高[1],并且开始小龄化,少年儿童高尿酸血症发生率有非常明显的上升。高尿酸血症与心血管疾病、慢性肾脏病、代谢综合征等相关,是危害人类健康的一种严重的代谢性疾病,是一个亟待解决的公共健康问题,也越来越受到广大医学界的重视。本文随机抽取青岛市区1200名7～15岁少年儿童体检资料,进行统计分析。     

过氧化物体增殖剂活化受体与脂质代谢紊乱

过氧化物体增殖剂活化受体(PPARs)属于核受体超家族.它在转录水平上调节脂质代谢,脂肪细胞分化和细胞因子的产生,在多代谢症侯群和动脉粥样硬化中发挥作用.调脂药fibrates和抗糖尿病药gliatazones等都是其人工合成的配体.PPARs可望成为新的药物作用的靶点并为代谢紊乱性疾病的研究提供新的思路.     

铁死亡在心血管疾病中的作用及研究进展

铁死亡是近年来发现的一种调节性细胞死亡方式,其特征为铁过载、脂质过氧化和活性氧积累等。铁死亡受铁代谢、脂质代谢和氨基酸代谢等多种代谢途径调控。在急性心肌梗死、心肌缺血再灌注损伤、心力衰竭和动脉粥样硬化等心血管疾病中,铁死亡发挥重要作用,与心肌细胞损伤密切相关。探讨铁死亡在心血管疾病中的作用及研究进展,以期为治疗心血管疾病提供新的靶点。     

浅谈南京市六合区学龄前儿童肥胖控制

随着社会经济的发展,人民生活水平的提高,我国儿童单纯性肥胖的发生率呈现上升的趋势,儿童肥胖已成为一个社会普遍关注的公共健康问题。众所周知,儿童肥胖不仅会造成社会适应能力、活动能力、社交能力等各种行为问题,而且极易延续到成年期。在儿童肥胖中有40%~70%可发展为成人肥胖症,并可增加成年期心血管疾病、高脂血症、高血压等代谢性疾病的发病风险。托幼机构的儿童正处于学龄前期,是个性发展的初始阶段,有研究表明,学龄前期是儿童肥胖控制的关键时期。本文通过参考目前国内儿童肥胖控制研究方法,结合本地区2006~2010年集体儿童报表肥胖发生率情况,探讨适合本地学龄前儿童单纯性肥胖控制的可行性方法。     

心肌纤维化发病机制及治疗的研究进展

随着全世界人口老龄化进程不断推进,纤维化相关的心血管疾病的发病率逐年升高,受到了学者们的广泛关注.心肌纤维化(myocardial fibrosis,MF)是一种以细胞外基质(extracellular matrix,ECM)成纤维细胞过度增殖、胶原沉积及异常分布为特征的疾病,是多种心血管疾病发展至终末的共同病理表现.其发病机制多样化(如RAAS系统的激活、TGF-β等),信号转导通路复杂,并与糖尿病、甲状腺疾病等全身代谢性疾病息息相关.研究MF的发病机制有助于预防心血管疾病的发生,为治疗提供思路.然而,MF的发生机制复杂,目前尚未完全阐明.     

皮下脂肪组织与内脏脂肪组织

肥胖不仅指过多的脂肪积聚,还包括脂肪的分布异常。内脏脂肪的增加是多种代谢性疾病（如2型糖尿病、心血管疾病等）的高危因素。脂肪组织通过分泌脂肪细胞因子和炎症因子调节胰岛索敏感性和参与胰岛素信号通路。因此,研究脂肪组织分布与内分泌特点对防治肥胖及其相关疾病具有重要的意义。     

肥胖儿童体质指数与血浆内皮素水平的关系及其干预措施

随着生活水平的提高和饮食结构的改变,儿童肥胖症呈逐年增多趋势,已接近发达国家水平。儿童肥胖的慢性代谢性疾病如高胰岛素血症、胰岛素抵抗、血脂代谢紊乱、高血压、脂肪肝等在儿童发病率越来越高,因而有效干预儿童肥胖症的研究迫在眉睫。有研究表明成年期心血管疾病的血管内皮细胞功能紊乱和动脉粥样硬化在儿童中已存在,     

mTOR介导转录因子调控细胞糖脂代谢的研究进展

哺乳动物雷帕霉素靶蛋白(mTOR)是一种重要的信号分子,参与体内蛋白质合成,细胞增殖、细胞周期、能量代谢和自噬等过程.mTOR的失活可导致肿瘤和代谢性疾病的发生.其中,HIF1α、c-Myc、FoxO1、SREBPs、PPARγ/PPARα及TFEB作为mTOR的下游信号,与细胞的糖脂代谢密切相关.     

TLRs介导引起的反应对机体的两面性

Toll样受体(Toll-like receptors,TLRs)是存在于机体的一类重要的模式识别受体,在免疫调节、血细胞的增殖和分化、机体的神经系统发育、肠道免疫耐受的调节、内分泌等方面都有着重要的作用。但是任何事物都有两面性,TLRs也不例外。TLRs介导引起的反应对机体还存在着弊端,TLRs的激活与心血管疾病、代谢性疾病、肺部疾病、肿瘤和肠道自身免疫疾病有很密切的关系。     

上游转录因子1基因多态性与代谢综合征研究进展

上游转录因子基因位于染色体上代谢综合征和2型糖尿病连锁分析重现率最高的区域(1q21-q25)内.该基因编码的蛋白属于碱性螺旋-环-螺旋-亮氨酸拉链家族的成员,可参与控制和调节糖、脂代谢相关基因的表达,因而可作为代谢综合征和2型糖尿病的重要候选基因.本文就上游转录因子1基因的结构、生物学特性以及与代谢综合征相关性状关系的研究进展进行了综述.     

On the metabolic basis of nervous activity

1. A study has been made of the metabolic substrates that can support the active extrusion of sodium ions from mammalian non-myelinated nerve fibres. The post-tetanic hyperpolarization obtained in chloride-free Locke solution, which reflects the electrogenic component of the sodium pump, was used as the index of metabolic activity.2. When glucose was removed from the Locke solution there was no immediate change in the size of the post-tetanic hyperpolarization.3. However, glucose is essential for metabolism in nerve fibres; for when a competitive inhibitor, deoxy-D-glucose, was added to the Locke solution the post-tetanic response was much reduced or abolished. Larger concentrations of deoxy-D-glucose were required in the presence of glucose than in its absence.4. This effect of deoxy-D-glucose could be reversed by glucose, fructose, pyruvate and acetate.5. The depressant effect of deoxy-D-glucose was enhanced by oxaloacetate and by malate.6. Malonate, a competitive inhibitor of the conversion of succinate to fumarate, reduced or abolished the post-tetanic hyperpolarization.7. This effect of malonate could be overcome by glucose and by pyruvate.     

Food intake and peripheral factors after recovery from insulin-induced hypoglycemia

Rats increased food intake after plasma glucose returned to normal in the wake of an insulin-induced hypoglycemic episode. Whereas increased eating 6-8 h after insulin occurred only when plasma glucose levels fell below 70 mg/dl, intakes were not related to the degree of prior hypoglycemia. Administration of glucose in the first 3 h after insulin prevented increased eating, whereas glucose given 4-6 h after insulin was less effective. Intravenous infusions of fructose given in the first 3 h after insulin injection prevented increased food intake in normal but not hepatic-vagotomized rats. Determination of various metabolic variables in parallel experiments showed that insulin treatment resulted in changes in peripheral metabolism, which persisted at the time feeding tests were conducted, and that administration of glucose or fructose tended to reverse these changes. The results suggest that increased food intake after recovery from hypoglycemia is associated with peripheral metabolic consequences of ongoing or previous counterregulatory responses which occur during hypoglycemia and that alterations in hepatic metabolism are sufficient to inhibit this insulin-induced eating.     

Transport and metabolism of fructose in fat cells of normal and hypophysectomized rats.

We have shown earlier that the glucose carrier of fat cells of hypophysectomized rats operates at maximal speed in the basal state and that these cells are insensitive to insulin. Here we characterize fructose transport and metabolism in adipocytes of normal and hypophysectomized rats. 3-O-methylglucose inhibits insulin-stimulated incorporation of [U-14C]fructose into fat cells and has no significant effect on basal fructose metabolism. In contrast, 2-deoxyglucose inhibits both basal and insulin-stimulated fructose incorporation. Insulin enhances fructose incorporation in normal adipocytes only in the absence of 3-O-methylglucose. In hypophysectomized rats, incorporation of glucose and of fructose is decreased and insensitive to insulin. In contrast to the glucose carrier, the specific fructose carrier appears to be insensitive to insulin and to continue to operate with unchanged characteristics after hypophysectomy. Thus, hypophysectomy leads to a specific alteration of the insulin-sensitive glucose carrier, whereas the insulin-insensitive fructose carrier remains unaltered.     

Parasitic Nematode-Induced Modulation of Body Weight and Associated Metabolic Dysfunction in Mouse Models of Obesity

Obesity is associated with a chronic low-grade inflammation characterized by increased levels of proinflammatory cytokines that are implicated in disrupted metabolic homeostasis. Parasitic nematode infection induces a polarized Th2 cytokine response and has been explored to treat autoimmune diseases. We investigated the effects of nematode infection against obesity and the associated metabolic dysfunction. Infection of RIP2-Opa1KO mice or C57BL/6 mice fed a high-fat diet (HFD) with Nippostrongylus brasiliensis decreased weight gain and was associated with improved glucose metabolism. Infection of obese mice fed the HFD reduced body weight and adipose tissue mass, ameliorated hepatic steatosis associated with a decreased expression of key lipogenic enzymes/mediators, and improved glucose metabolism, accompanied by changes in the profile of metabolic hormones. The infection resulted in a phenotypic change in adipose tissue macrophages that was characterized by upregulation of alternative activation markers. Interleukin-13 (IL-13) activation of the STAT6 signaling pathway was required for the infection-induced attenuation of steatosis but not for improved glucose metabolism, whereas weight loss was attributed to both IL-13/STAT6-dependent and -independent mechanisms. Parasitic nematode infection has both preventive and therapeutic effects against the development of obesity and associated features of metabolic dysfunction in mice.     

Regulation of longevity by FGF21: Interaction between energy metabolism and stress responses

Fibroblast growth factor 21 (FGF21) is a hormone-like member of FGF family which controls metabolic multiorgan crosstalk enhancing energy expenditure through glucose and lipid metabolism. In addition, FGF21 acts as a stress hormone induced by endoplasmic reticulum stress and dysfunctions of mitochondria and autophagy in several tissues. FGF21 also controls stress responses and metabolism by modulating the functions of somatotropic axis and hypothalamic-pituitary-adrenal (HPA) pathway. FGF21 is a potent longevity factor coordinating interactions between energy metabolism and stress responses. Recent studies have revealed that FGF21 treatment can alleviate many age-related metabolic disorders, e.g. atherosclerosis, obesity, type 2 diabetes, and some cardiovascular diseases. In addition, transgenic mice overexpressing FGF21 have an extended lifespan. However, chronic metabolic and stress-related disorders involving inflammatory responses can provoke FGF21 resistance and thus disturb healthy aging process. First, we will describe the role of FGF21 in interorgan energy metabolism and explain how its functions as a stress hormone can improve healthspan. Next, we will examine both the induction of FGF21 expression via the integrated stress response and the molecular mechanism through which FGF21 enhances healthy aging. Finally, we postulate that FGF21 resistance, similarly to insulin resistance, jeopardizes human healthspan and accelerates the aging process.     

High fructose diet: A risk factor for immune system dysregulation

Excessive intake of sweets is a predisposing factor for metabolic disorders, and fructose, as one of the major dietary sugars in the diet, has been shown to be a major cause of obesity, diabetes, and metabolic syndrome. These disorders are usually associated with immune dysfunction. Therefore, exploring the effects of a high fructose diet on the immune system may provide insight into the underlying mechanisms of these diseases. We synthesized the available evidence to suggest that excessive fructose intake disrupts the body's immune homeostasis by promoting immune cell metabolic rearrangements, alterations in gut microbial community structure, and intestinal barrier permeability. Indeed, not only does fructose itself affect immune system homeostasis, but its metabolites also have a profound influence. The metabolites from fructolysis are mainly produced in the small intestine and liver and subsequently enter the systemic circulation. Elevated levels of fructose metabolites, such as uric acid, FFAs, and lactate, are closely associated with oxidative stress and local tissue and organ inflammatory responses. In this review, we will focus on the link between fructose and inflammatory responses. In the meanwhile, we will also briefly summarize the studies of cancer development and immune escape mediated by fructose, as it might be beneficial for cancer immunotherapy.     

Expression of fructose sensitive glucose transporter in the brains of fructose-fed rats

Glucose transporters play a critical role in mammalian brain energy metabolism because glucose is the principal brain energy source and these transporters promote glucose movement into neural cells. When glucose is unavailable, fructose can serve as an alternative energy source. Using real-time polymerase chain reaction and actin as a reference mRNA, we investigated the impact of fructose feeding on rat brain and other tissue mRNA expression of glucose transporter 5 which has high affinity for fructose. Brain mRNA levels of glucose transporter 5 increased 1.5-fold in 35-day old rats after 7 days of fructose feeding compared with controls, whereas it increased 2.5-fold in jejunum. Semi-quantitative analysis of protein expression by immunofluorescence of glucose transporter 5 in rat hippocampi indicated a 2.4-fold increase. We demonstrated the specificity of fructose feeding on glucose transporter 5 expression by showing that the expression of the neuronal glucose transporter 3 and insulin-regulated glucose transporter 4 were unaffected. In addition, the expression of glucose transporter 5 increased in fructose fed older adult rats (8-months and 12-months old) when compared with controls. These results suggest that short-term fructose feeding increases the expression of glucose transporter 5 in both young and aging adult rats. Increased brain expression of glucose transporter 5 is likely to be important in the role of fructose as an alternative energy source.     

Adenosine increases calcium sensitivity via receptor-independent activation of the p38/MK2 pathway in mesenteric arteries

Derangements in whole body glucose and lipid metabolism, accompanied by insulin resistance, are key features of obesity and the metabolic syndrome. A role for inflammation as a causative factor is an emerging concept in the field of metabolic disease. Research has centred on identifying important inflammatory markers, and tumour necrosis factor‐α has been highlighted as a key mediator of insulin resistance, as well as interleukin‐6 (IL‐6). A parallel ongoing endeavour is the unravelling of molecular mechanisms underlying the beneficial effects of physical exercise on whole body glucose and lipid metabolism. Release of IL‐6 from the contracting skeletal muscle has been proposed to be one of the molecular signals promoting the beneficial exercise‐induced effects. These two opposing views of IL‐6 underscore that the role of IL‐6 in whole body physiology is incompletely resolved. This review aims at summarizing the current data on mechanisms by which IL‐6 may impact on glucose and lipid metabolism.