下丘脑的代谢与能量平衡调控功能研究进展

下丘脑是调控代谢稳态与能量平衡的关键脑区,对摄食、营养素代谢、机体水平衡、基础代谢、体温、生理节律等代谢相关功能发挥核心调控作用,维系机体异化作用与同化作用平衡。近年来,随着神经科学技术的发展,下丘脑参与代谢调控的神经核团、神经通路、及其机理被深入研究,并揭示出一系列重要的新发现。这些新发现,对深入理解肥胖及相关代谢疾病发病机制具重要意义。值得注意的是,下丘脑功能失调,与肥胖、二型糖尿病等代谢疾病发病密切相关。本文综述近年来有关下丘脑调控代谢和能量平衡研究进展,以期深入了解下丘脑调控代谢和能量平衡的神经与分子机制,并为相关疾病的诊疗提供新信息。     

下丘脑室旁核的心血管调节功能研究进展

下丘脑室旁核 (PVN)是自主性和内分泌性反应的重要整合中枢 ,且在维持心血管活动的动态平衡中起着关键作用。本文简要归纳了PVN的形态结构、纤维联系 ,并详细叙述其对心血管活动的调节及与心血管疾病的关系。     

儿茶酚胺调节免疫功能的细胞和分子机制

目前认为儿茶酚胺(cateeholamines,CAs)不只是引起普遍的免疫抑制,而是抑制细胞免疫但促进体液免疫。CAs可抑制1型辅助T(T helper 1,Th1)细胞、细胞毒性T(T cytotoxie,Tc)细胞、自然杀伤(natural kiHer,NK)细胞和单核细胞的作用,并增强Th2和B细胞的作用。CAs通过免疫细胞上的β2-肾上腺素受体(β2-adrenoreceptors,β2-ARs)引起细胞内cAMP增加,cAMP激活蛋白激酶A(protein kinase A,PKA),后者调节核转录因子的活性,从而影响细胞因子的基因表达,即抑制白介素-2(interleukin-2,IL-2)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和IL-12的基因转录;增强IL-6、IL-10和IL-4的基因表达。     

血清chemerin 水平与代谢综合征患者合并冠心病的相关性研究

目的:旨在探讨血清脂肪因子chemerin水平与代谢综合征患者合并冠心病的相关性。方法:共纳入116名代谢综合征患者,将所有患者分为两组,合并冠心病组(CAD+,n=47)及未合并冠心病组(CAD-,n=69),使用酶联免疫吸附(ELISA)法测量每组血清的血清chemerin水平。结果:CAD+组患者的血清chemerin水平较CAD-组患者显著升高(129.83±29.18 vs 94.01±23.54 ng/mL;P<0.01),多元Logistic回归分析结果显示血清chemerin水平与代谢综合征患者合并冠心病存在独立相关性(优势比1.565,95%可信区间1.104-2.876;P<0.05)。结论:血清chemerin水平是代谢综合征患者合并冠心病的独立危险因子,血清chemerin可能是预测代谢综合征患者发生冠心病风险的重要的生物学标记物。     

脂肪因子与代谢综合征关系的研究进展

代谢综合症是一系列代谢和心血管功能失调的临床特征,包括中心性肥胖、高血压、血脂异常、高血糖及胰岛素抵抗等,其发病机制及如何预防及控制代谢综合症正日益成为目前的学术热点。目前已经公认,脂肪不仅是能量存储器官,也是一个重要的内分泌器官。脂肪组织分泌的生物活性分子被称为脂肪因子。近年来的研究表明,脂肪因子广泛参与肥胖、2型糖尿病、高血压病及心血管疾病等一系列代谢相关性疾病的病理生理过程。脂肪因子能通过介导一系列的信号转导通路,并广泛参与机体复杂的代谢平衡网络的调节。脂肪因子的失衡能导致机体发生对胰岛素敏感性改变等一系列的生物学反应,从而在肥胖和代谢综合症的病理过程中发挥重要的作用。本文综述了脂肪因子与代谢综合征的关系的研究进展。     

代谢综合征：当今流行病

高血压、糖尿病和心脑血管梗塞等病症都来源于共同的发病基础——代谢综合征。现在该病的发病率越来越高，其病因主要包括遗传因素、肥胖症和缺乏运动等。这些疾病已成为现代人生命健康的杀手。因此医学界正在研究各种致病原因，以便能早期抑制这些病的发展。     

姜黄素治疗代谢综合征的研究进展

姜黄素是从姜黄中提取的一种多酚类物质,近年来对姜黄素的研究日趋广泛,已明确具有抗肿瘤,抗炎,抗氧化、降糖、降脂等多种药理作用,在临床上广泛应用于治疗肿瘤、肥胖、糖尿病等多种疾病.代谢综合征是一组以代谢紊乱为特征的症候群,包括中心性肥胖、糖脂代谢异常、高血压、非酒精性脂肪肝等,这些病理状态长期发展,可进一步导致心、脑血管患病率明显升高,研究发现姜黄素能够改善代谢综合征.现就近年来有关姜黄素治疗代谢综合征的研究进展综述如下.     

良性前列腺增生与代谢综合征相关性研究

目的:探讨代谢综合征在老年良性前列腺患者病程中的作用.方法:选择湖南师范大学第二附属医院老年病科2010年1月至2012年1月门诊及住院的男性良性前列腺增生合并代谢综合征患者88例,同时选择同期的单纯良性前列腺增生患者90例,分析体重指数、血压、腰围、空腹血糖、胰岛素抵抗指数、总胆固醇、甘油三酯、低密度脂蛋白、高密度脂蛋白、前列腺特异性抗原等对及前列腺体积的影响.结果:BPH合并MS组PV为(39.7±21.1)mL,明显高于单纯BPH组,且PV与BMI、收缩压、空腹血糖、PSA呈正相关,与高密度脂蛋白呈负相关.结论:BPH与MS具有相关性,BMI、收缩压、PSA、FBG、低密度脂蛋白是BPH发生发展的危险因素.     

Hypothalamic lipotoxicity and the metabolic syndrome

Ectopic accumulation of lipids in peripheral tissues, such as pancreatic β cells, liver, heart and skeletal muscle, leads to lipotoxicity, a process that contributes substantially to the pathophysiology of insulin resistance, type 2 diabetes, steatotic liver disease and heart failure. Current evidence has demonstrated that hypothalamic sensing of circulating lipids and modulation of hypothalamic endogenous fatty acid and lipid metabolism are two bona fide mechanisms modulating energy homeostasis at the whole body level. Key enzymes, such as AMP-activated protein kinase (AMPK) and fatty acid synthase (FAS), as well as intermediate metabolites, such as malonyl-CoA and long-chain fatty acids-CoA (LCFAs-CoA), play a major role in this neuronal network, integrating peripheral signals with classical neuropeptide-based mechanisms. However, one key question to be addressed is whether impairment of lipid metabolism and accumulation of specific lipid species in the hypothalamus, leading to lipotoxicity, have deleterious effects on hypothalamic neurons. In this review, we summarize what is known about hypothalamic lipid metabolism with focus on the events associated to lipotoxicity, such as endoplasmic reticulum (ER) stress in the hypothalamus. A better understanding of these molecular mechanisms will help to identify new drug targets for the treatment of obesity and metabolic syndrome.     

Hypothalamic adrenergic receptor changes in the metabolic syndrome of genetically obese (ob/ob) mice

The genetically, seasonally, and diet-induced obese, glucose-intolerant states in rodents, including ob/ob mice, have each been associated with elevated hypothalamic levels of norepinephrine (NE). With the use of quantitative autoradiography on brain slices of 6-wk-old obese (ob/ob) and lean mice, the adrenergic receptor populations in several hypothalamic nuclei were examined. The binding of [(125)I]iodocyanopindolol to beta(1)- and beta(2)-adrenergic receptors in ob/ob mice was significantly increased in the paraventricular hypothalamic nucleus (PVN) by 30 and 38%, in the ventromedial hypothalamus (VMH) by 23 and 72%, and in the lateral hypothalamus (LH) by 10 and 15%, respectively, relative to lean controls. The binding of [(125)I]iodo-4-hydroxyphenyl-ethyl-aminomethyl-tetralone to alpha(1)-adrenergic receptors was also significantly increased in the PVN (26%), VMH (67%), and LH (21%) of ob/ob mice. In contrast, the binding of [(125)I]paraiodoclonidine to alpha(2)-adrenergic receptors in ob/ob mice was significantly decreased in the VMH (38%) and the dorsomedial hypothalamus (17%) relative to lean controls. This decrease was evident in the alpha(2A)- but not the alpha(2BC)-receptor subtype. Scatchard analysis confirmed this decreased density of alpha(2)-receptors in ob/ob mice. Together with earlier studies, these changes in hypothalamic adrenergic receptors support a role for increased hypothalamic NE activity in the development of the metabolic syndrome of ob/ob mice.     

Early endocrine and molecular changes in metabolic syndrome models

The twenty-first century arrived in the middle of a global epidemic of metabolic syndrome (MS) and type 2 diabetes mellitus (DM2). It is generally accepted that an excess of nutrients linked to a low physical activity triggers the problem. However, the molecular features that interact to develop the MS are not clear. In an effort to understand and control them, they have been extensively studied, but this goal has not been achieved yet. Nonhuman animal models have been used to explore diet and genetic factors in which experimental conditions are controlled. For example, only one factor in the diet, such as fats or carbohydrates can be modified to better understand a single change that would be impossible in humans. Most of the studies have been done in rodents. However, it is difficult to directly compare them, because experiments are different in more than one variable; genetic strains, amount, and the type of fat used in the diet and sex. Thus, the only possible criteria of comparison are the relevance of the observed changes. We review different animal models and add some original observations on short-term changes in metabolism and beta cells in our own model of adult Wistar rats that are not especially prone to get fat or develop DM2, treated with 20% sucrose in drinking water. One early change observed in pancreatic beta cells is the increase in GLUT2 expression that is located to the membrane of the cells. This change could partially explain the presence of insulin hypersecretion and hyperinsulinemia in these rats. Understanding early changes that lead to MS and in time to pancreatic islet exhaustion is an important biomedical problem that may contribute to learn how to prevent or even reverse MS, before developing DM2.     

Antioxidative status changes in golden syrian hamsters with experimental metabolic syndrome

Some indices of the antioxidant status (content of the alpha-tocopherol, reduced glutathione and ascorbic acid, activity of the glutathione reductase and aryl-esterase) and lipid peroxidation processes in the liver, blood serum, and some blood serum lipoprotein fractions of the Golden Syrian hamsters of different sex and age status under high-caloric diet were investigated. It has been shown that the hypercaloric diet leads to a decreaseng of reduced glutathione content and increase of the level of lipid peroxidation products in the liver of experimental animals. The ascorbic acids content in male liver is decreased and in female liver is increased. In the blood serum under hypercaloric nutrition the accumulation of lipid peroxidation products and alpha-tocopherol content a decrease in ApoB-lipoproteins and HDL is observed. Simultaneously the ascorbic acid content is increased in the blood serum of all experimental animals. Activation of free-radical oxidation both in the liver, and blood serum is more significant in males compared with females. The data obtained allow to suppose that atherosclerotic complications of metabolic syndrome development may be connected to the lipoprotein oxidant status infringement.     

Seasonal changes in mood and behavior are linked to metabolic syndrome

Background

Obesity is a major public health problem worldwide. Metabolic syndrome is a risk factor to the cardiovascular diseases. It has been reported that disruptions of the circadian clockwork are associated with and may predispose to metabolic syndrome.

Methodology and Principal Findings

8028 individuals attended a nationwide health examination survey in Finland. Data were collected with a face-to-face interview at home and during an individual health status examination. The waist circumference, height, weight and blood pressure were measured and samples were taken for laboratory tests. Participants were assessed using the ATP-III criteria for metabolic syndrome and with the Seasonal Pattern Assessment Questionnaire for their seasonal changes in mood and behavior. Seasonal changes in weight in particular were a risk factor of metabolic syndrome, after controlling for a number of known risk and potential confounding factors.

Conclusions and Significance

Metabolic syndrome is associated with high global scores on the seasonal changes in mood and behavior, and with those in weight in particular. Assessment of these changes may serve as a useful indicator of metabolic syndrome, because of easy assessment. Abnormalities in the circadian clockwork which links seasonal fluctuations to metabolic cycles may predispose to seasonal changes in weight and to metabolic syndrome.     

The diet-induced metabolic syndrome is accompanied by whole-genome epigenetic changes

Consuming a high-fat/high-fructose diet (HFD) starting at a young age leads to the development of obesity and to the progression of metabolic syndrome (MS). We are interested in the relationship between MS and DNA methylation as a mediator of the metabolic memory and the early appearance of these diseases in the progeny. To this end, Wistar rats were fed a HFD for 1 year, and every 12 weeks, biochemical analyses were performed. After 24 weeks, animals fed the HFD showed alterations related to MS such as elevated blood levels of fasting glucose, triglycerides, and insulin compared with their littermate controls. During the experimental period, the control females exhibited a 40 % lower 5-methylcytosine (5-mC) level compared to the control males. The HFD affected the 5-mC levels in males and females differently. The HFD induced a 20 % decrease in the 5-mC levels in males and a 15 % increase in females. We found that the HFD induces an early presentation of MS in the progeny of treated animals and that the DNA methylation was altered in the F₁ generation. The presentation of MS is positively associated with changes in the global percentage of 5-mC in the DNA.     

Hypothalamic pregnenolone mediates recognition memory in the context of metabolic disorders

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