新脂肪因子nesfatin-1

肥胖日益成为危害人类健康的重大因素,而且研究表明它的发生主要来源于能量摄入和消耗之间的不平衡。大量研究主要集中于下丘脑对能量平衡的长期调节,因为下丘脑中存在丰富的调节摄食的多肽。另外,有研究发现外周同样也存在调节摄食的多肽,如胃肠道、脂肪组织等,它们在机体稳态维持中也发挥重要作用。nesfatin-1是一个新发现抑制食欲的多肽,它的氨基酸序列在人类和鼠类之间有高度的保守性。一系列     

脂肪细胞激素和细胞因子在能量平衡调节中的作用

肥胖与糖尿病、高血压,心脑血管疾病的发病密切相关,深入了解机体能平衡调节机制,驿防治肥胖和上述疾病有重要意义,脂肪细胞不但储能,同时通过它表达分泌各种激素和细胞因子,如瘦素,解偶联蛋白及肿瘤坏死因子等参与机体能量平衡的调节。脂肪细胞与胰岛之间亦有相互调节作用,并同参与机体的糖代谢脂肪代谢和能量代谢调节。     

食欲肽与肥胖抵抗

肥胖症是威胁现代人健康的重要疾病,它增加了糖尿病、高血压、高脂血症等疾病的发病率。肥胖的根本原因是机体能量摄入和消耗的失衡。食欲肽(orexin)是由下丘脑特异性分泌的一种能调节睡眠、摄食及能量平衡的神经肽。新近的研究表明,增加食欲肽水平和/或食欲肽的敏感性可通过提高机体自发活动(spontaneous physical activity,SPA)诱导的非运动生热作用(nonexercise activity thermogenesis,NEAT)而实现肥胖抵抗,进而开辟了一条治疗肥胖的新途径。该文综述了受食欲肽调控的SPA和NEAT与肥胖抵抗的关系,分析了食欲肽受体信号通路与肥胖的相关性,并阐释了食欲肽作为预防和治疗肥胖的分子靶标的作用机理。     

肥胖基因及其受体与脂肪沉积调控

多年来的研究表明 ,哺乳动物能量平衡应该受到反馈回路的控制 ,回路中下丘脑可以感应能量贮存量 ,继而调节采食量和能量支出以保持平衡体重。此假说源于一种脂肪组织产物通过在血浆中循环作用于下丘脑影响能量平衡。试验表明 ,肥胖鼠不能产生足量的饱食因子调节其食物消耗 ,而ｄｂ鼠虽能产生饱食因子 ,但因饱食中枢缺陷而不能对其起反应。1 .肥胖基因的克隆表达及其多态性随着分子生物学技术的出现和发展 ,肥胖基因被克隆测序 ,终于发现了ｏｂ/ｏｂ小鼠的特定基因缺陷 (Ｚｈａｎｇ等 ,1 994) ,由于基因突变 ,ｏｂ/ｏｂ小鼠不能产生瘦蛋白。…     

食欲肽及其受体

以前认为在下丘脑的腹内侧区及下丘脑外侧区分别存在饱中枢（ｓａｔｉｅｔｙｃｅｎｔｅｒ）及摄食中枢（ｆｅｅｄｉｎｇｃｅｎｔｅｒ）,进行机体能量平衡的中枢性调节。但随着许多参与机体能量平衡调节的神经递质及神经肽的发现,说明机体能量平衡的中枢性调节并非如此简...     

瘦蛋白的研究进展

瘦蛋白的研究进展黄君富房殿春（第三军医大学西南医院分子生物学实验室,重庆６３００３８）关键词瘦蛋白瘦蛋白受体肥胖基因肥胖是机体能量平衡紊乱的结果。当能量摄取超过能量消耗时,多余的能量便贮存于脂肪细胞,最终导致肥胖。对机体能量平衡及脂肪贮存进行更深入的...     

下丘脑Kiss1神经元在能量代谢调节中的作用

代谢是机体生存和延续的基础,机体通过影响行为并诱发一系列的生理反应,调节代谢状态。能量代谢失衡可能导致机体消瘦或肥胖,甚至会造成生长发育和生殖功能的障碍等。因此,维持机体的能量平衡至关重要,而这一状态的维持受中枢神经系统的严格控制。中枢神经系统,特别是下丘脑,在调节机体生理功能和能量平衡中发挥着重要的作用。下丘脑Kisspeptin被认为在调节性腺轴、营养性发育和生殖中发挥重要作用。近些年来,关于其在能量代谢调控中的作用也引起广泛关注。本文将从能量摄入和能量消耗两个方面对下丘脑Kisspeptin在能量代谢调控中的作用进行综述,以期为防治因能量失衡诱发的代谢性疾病提供新的研究思路和依据。     

褐色脂肪组织代谢与肥胖

肥胖是由于机体能量储存与消耗的失衡而产生的.褐色脂肪组织通过产热的形式,能够将体内过多的能量释放出来,以减少能量积累,避免造成肥胖.现从褐色脂肪组织的结构、分布、功能以及调控机制等方面,对褐色脂肪组织与肥胖症的关系作一综述,旨在为防治肥胖症及相关疾病寻找理论基础和实验依据.     

肥胖发病机制及其治疗靶点

人体摄入的食物提供的能量用来维持各种生理和体力活动的正常进行.在生理状态下,能量代谢保持动态平衡,即摄入能量=消耗能量+贮存能量.当由于某种原因打破这一平衡使能量的摄入大于消耗时,机体储能的主要器官--脂肪组织内脂肪(主要为甘油三酯)堆积,体重超过标准体重20％以上者,称为肥胖.随着社会经济的发展和人民生活水平的提高,全球范围内超重/肥胖率急剧增加.肥胖与高甘油三酯血症、高血压、糖尿病在发病机理上密切相关,这些慢性疾病相互影响并常在同一个体聚集存在,肥胖引起的这种交互紊乱更是诱发和加重心脑血管疾病的重要危险因素.因此,研究和分析与肥胖相关的因素及相互关系,有助于肥胖的预防和治疗.     

限制能量平衡膳食联合运动干预对肥胖儿童身体成分、脂质代谢及肠道菌群的影响

摘要 目的：观察限制能量平衡膳食联合运动干预对肥胖儿童身体成分、脂质代谢及肠道菌群的影响。方法：选取2020年4月至2022年10月期间浙江大学医学院附属儿童医院收治的肥胖儿童104例作为研究对象。按照随机数字表法将肥胖儿童分为对照组（n=52,限制能量平衡膳食）和观察组（n=52,限制能量平衡膳食联合运动干预）。对比两组身体成分、脂质代谢及肠道菌群变化情况。结果：观察组干预2个月后体重、体质量指数（BMI）、去脂体重、脂肪量、体脂率低于对照组（P<0.05）。观察组干预2个月后总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）低于对照组;高密度脂蛋白胆固醇（HDL-C）高于对照组（P<0.05）。观察组干预2个月后肠球菌、大肠杆菌低于对照组;乳杆菌、双歧杆菌高于对照组（P<0.05）。结论：限制能量平衡膳食联合运动干预可有效改善肥胖儿童身体成分,调节脂质代谢及肠道菌群平衡。     

Intracerebroventricular administration of vasoactive intestinal peptide inhibits food intake

Vasoactive intestinal peptide (VIP) is a 28 amino acid peptide expressed throughout the peripheral and central nervous systems. VIP and the VIP receptor VPAC(2)R are expressed in hypothalamic nuclei involved in the regulation of energy homeostasis. VIP has been shown to be involved in the regulation of energy balance in a number of non-mammalian vertebrates. We therefore examined the effects of intracerebroventricular (ICV) administration of VIP on food intake, energy expenditure and activity in adult male Wistar rats. VIP administration caused a potent short lived decrease in food intake and an increase in activity and energy expenditure. The pathways potentially involved in the anorexigenic effects of VIP were investigated by measuring the release of neuropeptides involved in the regulation of food intake from hypothalamic explants treated with VIP. VIP significantly stimulated the release of the anorexigenic peptide alpha-melanocyte stimulating hormone (αMSH). These studies suggest that VIP may have an endogenous role in the hypothalamic control of energy homeostasis.     

Hypothalamic malonyl-coenzyme A and the control of energy balance

An intermediate in the fatty acid biosynthetic pathway, malonyl-coenzyme A (CoA), has emerged as a major regulator of energy homeostasis not only in peripheral metabolic tissues but also in regions of the central nervous system that control satiety and energy expenditure. Fluctuations in hypothalamic malonyl-CoA lead to changes in food intake and peripheral energy expenditure in a manner consistent with an anorexigenic signaling intermediate. Hypothalamic malonyl-CoA is regulated by nutritional and endocrine cues including glucose and leptin, respectively. That malonyl-CoA is an essential component in the energy homeostatic signaling system of the hypothalamus is supported by convergence of physiological, pharmacological, and genetic evidence. This review will focus on evidence implicating malonyl-CoA as a central player in the control of body weight and adiposity as well as clues to the molecular mechanism by which carbon flux through the fatty acid biosynthetic pathway is linked to the neural control of energy balance.     

Functional Heterogeneity of Arcuate Nucleus Pro-Opiomelanocortin Neurons: Implications for Diverging Melanocortin Pathways

Arcuate nucleus (ARC) pro-opiomelanocortin (POMC) neurons are essential regulators of food intake, energy expenditure, and glucose homeostasis. POMC neurons integrate several key metabolic signals that include neurotransmitters and hormones. The change in activity of POMC neurons is relayed to melanocortin receptors in distinct regions of the central nervous system. This review will summarize the role of leptin and serotonin receptors in regulating the activity of POMC neurons and provide a model in which different melanocortin pathways regulate energy and glucose homeostasis.     

Brain-derived neurotrophic factor: Its role in energy balance and cancer cachexia

Brain-derived neurotrophic factor (BDNF) plays an important role in the development of the central and peripheral nervous system during embryogenesis. In the mature central nervous system, BDNF is required for the maintenance and enhancement of synaptic transmissions and the survival of neurons. Particularly, it is involved in the modulation of neurocircuits that control energy balance through food intake, energy expenditure, and locomotion. Regulation of BDNF in the central nervous system is complex and environmental factors affect its expression in murine models which may reflect to phenotype dramatically. Furthermore, BDNF and its high-affinity receptor tropomyosin receptor kinase B (TrkB), as well as pan-neurotrophin receptor (p75^NTR) is expressed in peripheral tissues in adulthood and their signaling is associated with regulation of energy balance. BDNF/TrkB signaling is exploited by cancer cells as well and BDNF expression is increased in tumors. Intriguingly, previously demonstrated roles of BDNF in regulation of food intake, adipose tissue and muscle overlap with derangements observed in cancer cachexia. However, data about the involvement of BDNF in cachectic cancer patients and murine models are scarce and inconclusive. In the future, knock-in and/or knock-out experiments with murine cancer models could be helpful to explore potential new roles for BDNF in the development of cancer cachexia.     

Appetite regulation: The central role of melatonin in Danio rerio

Melatonin is the hormonal mediator of photoperiodic information to the central nervous system in vertebrates and allows the regulation of energy homeostasis through the establishment of a proper balance between energy intake and energy expenditure. The aim of this study was to evaluate the role of melatonin in appetite central control analyzing the involvement of this hormone in the regulation of feeding behavior in the zebrafish Danio rerio. For this purpose, the effect of two different melatonin doses (100 nM and 1 μM) administered for 10 days, via water, to zebrafish adults was evaluated at both physiological and molecular level and the effect of melatonin was considered in relation to the most prominent systems involved in appetite regulation. For the first time, in fact, melatonin control of food intake by the modulation of leptin, MC4R, ghrelin, NPY and CB1 gene expression was evaluated.The results obtained indicate that melatonin significantly reduces food intake and the reduction is in agreement with the changes observed at molecular level. A significant increase in genes codifying for molecules involved in feeding inhibition, such as leptin and MC4R, and a significant reduction in the major orexigenic signals including ghrelin, NPY and CB1 are showed here.Taken together these results support the idea that melatonin falls fully into the complex network of signals that regulate food intake thus playing a key role in central appetite regulation.     

Leptina: un péptido con potencial terapéutico en sujetos obesos

Obesity is the result of a positive balance between total energy intake and its catabolism. Although many factors are involved in the regulation of energy metabolism, the discovery of leptin led to energy homeostasis being investigated in greater depth. Since its identification, leptin has been considered important in the development of obesity, given its anorexigenic effect and influence on food intake and energy expenditure. Leptin is involved in diverse physiological processes such as energy balance, appetite and body weight control, fat and carbohydrate metabolism, and reproduction. However, to be able to function, this hormone has many specific receptors both centrally (hypothalamus) and peripherally in the skeletal muscle, lungs and kidneys. This study aims to review the key aspects relating leptin to the development of obesity and discusses its potential as an anorectic agent.     

Nutritional modulation of leptin expression and leptin action in obesity and obesity-associated complications

In obesity, an elevated accumulation and dysregulation of adipose tissue, due to an imbalance between energy intake and energy expenditure, usually coexists with the loss of responsiveness to leptin in central nervous system, and subsequently with hyperleptinemia. Leptin, a peptide hormone mainly produced by white adipose tissue, regulates energy homeostasis by stimulating energy expenditure and inhibiting food intake. Human obesity is characterized by increased plasma leptin levels, which have been related with different obesity-associated complications, such as chronic inflammatory state (risk factor for diabetes, cardiovascular and autoimmune diseases), as well as infertility and different types of cancer. Besides, leptin is also produced by placenta, and high leptin levels during pregnancy may be related with some pathological conditions such as gestational diabetes. This review focuses on the current insights and emerging concepts on potentially valuable nutrients and food components that may modulate leptin metabolism. Notably, several dietary food components, such as phenols, peptides, and vitamins, are able to decrease inflammation and improve leptin sensitivity by up- or down-regulation of leptin signaling molecules. On the other hand, some food components, such as saturated fatty acids may worsen chronic inflammation increasing the risk for pathological complications. Future research into nutritional mechanisms that restore leptin metabolism and signals of energy homeostasis may inspire new treatment options for obesity-related disorders.     

Endocannabinoids and liver disease. IV. Endocannabinoid involvement in obesity and hepatic steatosis

Endocannabinoids are endogenous lipid mediators that interact with the same receptors as plant-derived cannabinoids to produce similar biological effects. The well-known appetitive effect of smoking marijuana has prompted inquiries into the possible role of endocannabinoids in the control of food intake and body weight. This brief review surveys recent evidence that endocannabinoids and their receptors are involved at multiple levels in the control of energy homeostasis. Endocannabinoids are orexigenic mediators and are part of the leptin-regulated central neural circuitry that controls energy intake. In addition, they act at multiple peripheral sites including adipose tissue, liver, and skeletal muscle to promote lipogenesis and limit fat elimination. Their complex actions could be viewed as anabolic, increasing energy intake and storage and decreasing energy expenditure, as components of an evolutionarily conserved system that has insured survival under conditions of starvation. In the era of plentiful food and limited physical activity, pharmacological inhibition of endocannabinoid activity offers benefits in the treatment of obesity and its hormonal/metabolic consequences.