棕色脂肪组织的形成及其作用机制

人体内脂肪组织分为棕色脂肪组织(BAT)和白色脂肪组织(WAT).它们在组织形态和生理作用上存在较大差异,BAT主要在寒冷环境或交感神经兴奋下参与产热过程,而WAT主要以甘油三酯的形式储存多余能量.通过对BAT形成和作用机制的研究发现,两种脂肪组织的起源不同,并且揭示出部分细胞因子与BAT形成及活化之间的复杂关系,从而...     

棕色脂肪组织移植减肥和改善糖脂代谢的研究进展

棕色脂肪组织（BAT）是人体非颤栗性产热的主要场所。多项研究证明,移植BAT具有减轻体重、改善糖代谢、逆转1型糖尿病等重要作用,作用机制包括激活内源性BAT、促进产热相关基因的表达、增加机体能量消耗、通过分泌棕色脂肪细胞因子改善糖脂代谢、减轻脂肪组织炎症。BAT在能量调节和全身代谢中发挥的作用为减肥及改善糖脂代谢异常提...     

棕色脂肪组织特异性基因在抵抗肥胖中作用的研究

目的通过研究高脂饮食诱导肥胖与肥胖抵抗大鼠肩胛间棕色脂肪组织中UCP-1、PGC-1α、Dio-2的表达情况以及电针刺激对肥胖大鼠UCP-1、PGC-1α表达的影响,探讨棕色脂肪组织特异性基因在抵抗肥胖中的作用。方法 40只雄性SD大鼠,按体重随机分为高脂实验组(n=28)和基础对照组(n=12)。分别给予高脂饲料和基础饲料喂养。高脂饮食5周末,将高脂实验组大鼠体重大于基础对照组最大体重者归为饮食诱导肥胖大鼠(DIO),将高脂实验组大鼠体重低于对照组平均体重者归为饮食诱导肥胖抵抗大鼠(DIO-R)。从DIO随机取6只为肥胖组(n=6)与肥胖抵抗组(n=6)、基础对照组(n=6),比较各组大鼠体重、两种脂肪重水平,使用实时荧光定量PCR及Western blot方法比较三组肩胛间棕色脂肪组织中UCP-1、PGC-1α、Dio-2表达水平的差异。在DIO大鼠中再取10只随机分为:肥胖组(Ob组,n=5)、电针刺激组(EA组,n=5)与基础对照组(n=5)以基础饲料适应性喂养1周后,其中EA组选取足三里、三阴交给予电针刺激,每周3次,每次30 min,观察摄食量及体重变化。6周后使用实时荧光定量PCR及Westernblot方法比较3组大鼠棕色脂肪组织中UCP-1、PGC-1α表达水平的差异。结果 DIO组明显高于DIO-R组,DIO-R组大鼠肩胛间棕色脂肪组织重及Dio-2、PGC-1α、UCP-1mRNA表达水平明显高于DIO大鼠(P<0.05)。高脂组大鼠PGC-1α、Dio-2m RNA表达水平均低于对照组大鼠(P<0.05);DIO-R组大鼠UCP-1 mRNA表达水平高于对照组大鼠(P<0.05)。DIO大鼠UCP-1蛋白水平表达低于基础对照组及DIO-R大鼠(P<0.05)。电针刺激6周后,电针刺激组大鼠棕色脂肪组织中UCP-1、PGC-1αmRNA及蛋白水平表达均高于Ob组及对照组(P<0.05)。电针刺激组大鼠体重、摄食量低于肥胖组大鼠(P<0.05)。结论高脂饮食条件下,SD大鼠表现为明显的肥胖易感性差异。饮食诱导肥胖抵抗大鼠棕色脂肪组织重及特异性基因表达升高。电针刺激增加了棕色脂肪组织特异性基因表达,减少摄食量。棕色脂肪组织特异性基因表达在抵抗肥胖中有重要作用。     

脂肪组织棕色化与动脉粥样硬化的关系研究进展

脂肪组织棕色化会影响动脉粥样硬化的进展。本综述首先介绍环境温度改变对动脉粥样硬化的影响,接着介绍多种方法诱导脂肪组织棕色化对动脉粥样硬化的影响,最后介绍铁代谢在脂肪组织棕色化中的作用以及通过铁代谢调节脂肪组织棕色化治疗动脉粥样硬化的新思路,总结了脂肪组织棕色化与动脉粥样硬化的关系研究进展。     

白色脂肪棕色化及其调控因素

近年,对脂肪组织的起源、分化、作用及调节的认识有了新的进展.体内的白色脂肪组织负责储存能量并分泌一些脂肪因子参与各种代谢性疾病的发生,而棕色脂肪组织主要负责产热和消耗能量.因此,“白色脂肪棕色化”对肥胖及许多相关疾病有着巨大的治疗潜力,可为这些疾病的治疗提供新的选择.“白色脂肪棕色化”这一过程受多种因素调控,如多种转录调节剂、蛋白质和激素等,因此未来可通过干预这些调控因素来研究相关疾病的新治疗方法.     

脂肪组织的内分泌功能

近期研究发现，脂肪组织不仅是能量储存器官，还是通过分泌各种激素及细胞因子参与能量代谢及肥胖相关疾病发生的内分泌器官。瘦素是一种饱食因子，它的主要功能是调节能量平衡，另外还能够影响神经内分泌及免疫功能。脂肪组织的性激素及糖皮质激素代谢决定了体脂分布，参与心血管病的发生。其它一些由脂肪组织产生的蛋白质，如前炎症细胞因子、补体、纤溶凝血成分也介导了与肥胖有关的心血管及代谢病的发生。     

脂肪组织的内分泌功能

近期研究发现 ,脂肪组织不仅是能量储存器官 ,还是通过分泌各种激素及细胞因子参与能量代谢及肥胖相关疾病发生的内分泌器官。瘦素是一种饱食因子 ,它的主要功能是调节能量平衡 ,另外还能够影响神经内分泌及免疫功能。脂肪组织的性激素及糖皮质激素代谢决定了体脂分布 ,参与心血管病的发生。其它一些由脂肪组织产生的蛋白质 ,如前炎症细胞因子、补体、纤溶凝血成分也介导了与肥胖有关的心血管及代谢病的发生     

髓源性生长因子对肥胖小鼠白色脂肪棕色化的影响

目的:探讨髓源性生长因子（MYDGF）对肥胖小鼠白色脂肪棕色化的影响。方法:高脂饲料喂养雄性C57BL/6J野生型（WT）小鼠和MYDGF基因敲除（KO）小鼠12周,根据使用腺相关病毒（AAV）-MYDGF或AAV-绿色荧光蛋白（GFP）干预,将WT和KO小鼠分为WT-GFP组、WT-MYDGF组、KO-GFP组和KO...     

棕色脂肪组织与糖代谢的关系

研究证实成人体内存在有活性的棕色脂肪组织(BAT).BAT是非颤栗产热和饮食诱导产热的主要器官,其产热作用依赖线粒体内膜的解耦联蛋白1(UCP1).UCP1可使物质氧化与ATP生成解耦联(解耦联呼吸),减少ATP的生成,使能量以热量的形式释放,维持体温与能量的平衡.寒冷暴露、胰岛素、去甲肾上腺素、甲状腺激素等均可诱导UCP1表达使BAT活化,进而促进BAT摄取循环中的葡萄糖,加速循环中葡萄糖的清除.饮食因素以及可诱导BAT活化的因素均可影响BAT对葡萄糖的摄取.     

高脂饮食诱导肥胖小鼠不同脂肪组织炎症反应相关基因表达及其机制

目的 探讨高脂饮食诱导肥胖小鼠不同脂肪组织炎症反应相关基因表达及其机制。方法 将10只小鼠随机分为正常饮食对照组（ND组）、高脂饮食模型组（HFD组）各5只,分别喂以常规饲料、高脂饲料,饲喂10周。将小鼠颈部脱臼处死,取肩胛间棕色脂肪组织（BAT）、腹股沟白色脂肪组织（iWAT）、附睾白色脂肪组织（eWAT）。将各脂肪组织进行转录组测序（seq）,并对测序结果进行质量评估以及主成分分析（PCA）。筛选三种脂肪组织中的差异表达基因,并对其进行基因本体论（GO）功能富集分析和京都基因与基因组百科全书（KEGG）通路富集分析;筛选表达上调最明显的前20个炎症反应相关基因。结果 HFD组较ND组体质量水平高（P<0.05）。两组脂肪组织seq质量评估结果显示错误率<0.1%,Q20>85%,Q30>80%。PCA显示两个主成分方差贡献率分别为51.81%、19.08%。iWAT中HFD组表达上调基因2 548个,eWAT中HFD组表达上调基因3 384个,BAT中HFD组表达上调基因1 630个;iWAT中HFD组表达下调基因2 082个,eWAT中HFD组表达下调基因...     

棕色脂肪检测技术的研究进展

目前关于体内棕色脂肪的检测主要分为半定量检测和功能检测两大类.半定量检测方法主要包括正电子发射断层扫描(PET)/CT、MRI等影像学检查,功能检测方法主要包括间接热量测定法、交感神经张力测定法、测温法等.此外,还可以通过称重法、检测棕色脂肪经典标志物表达来评估.对棕色脂肪组织的检测有助于进一步探讨肥胖的发生机制,从而为其治疗提供新的靶点.     

The role of brown adipose tissue in human obesity

It is widely accepted that newborn humans are provided with brown adipose tissue (BAT) and that adult humans lack, or have only a small amount, of it. Therefore the physiological role of BAT in humans is debated. It is quite clear that BAT in rodents has an important role in the prevention and therapy of obesity and diabetes and specific drugs can induce BAT development in adult animals. New concepts regarding the biology of adipose tissues in mammals have been developed during the last years leading to the hope for the development of BAT in human adults as a new challenge for the treatment of obesity and related diseases. These new concepts are basic to understanding the above-proposed therapeutic strategy and are the concept of the adipose organ and the concept of transdifferentiation. In this paper these new concepts will be explained together with a review of available scientific data on human BAT.     

A synopsis of brown adipose tissue imaging modalities for clinical research

Body weight gain results from a chronic excess of energy intake over energy expenditure. Accentuating endogenous energy expenditure has been accorded considerable attention ever since the presence of brown adipose tissue (BAT) in adult humans was recognized, given that BAT is known to increase energy expenditure via thermogenesis. Besides classic BAT, significant strides in our understanding of inducible brown adipocytes have been made regarding its development and function. While it is ideal to study BAT histologically, its relatively inaccessible anatomical locations and the inherent risks associated with biopsy preclude invasive techniques to evaluate BAT on a routine basis. Thus, there has been a surge in interest to employ non-invasive methods to examine BAT. The gold standard of non-invasive detection of BAT activation is ¹⁸F-fluorodeoxyglucose positron emission tomography (PET) with computed tomography (CT). However, a major limitation of PET/CT as a tool for human BAT studies is the clinically significant doses of ionizing radiation. More recently, several other imaging methods, including single-photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), infrared thermography (IRT)/thermal imaging and contrast ultrasonography (US) have been developed in hopes that they would allow non-invasive, quantitative measures of BAT mass and activity with lower costs. This review focuses on such methods to detect human BAT activation and white adipose tissue (WAT) browning to prompt the establishment of BAT-centric strategies for augmenting energy expenditure and combatting obesity. Clinical validation of these methods will most likely expand the scope and flexibility of future BAT studies.     

Factors involved in white‐to‐brown adipose tissue conversion and in thermogenesis: a review

Obesity is the result of energy intake chronically exceeding energy expenditure. Classical treatments against obesity do not provide a satisfactory long‐term outcome for the majority of patients. After the demonstration of functional brown adipose tissue in human adults, great effort is being devoted to develop therapies based on the adipose tissue itself, through the conversion of fat‐accumulating white adipose tissue into energy‐dissipating brown adipose tissue. Anti‐obesity treatments that exploit endogenous, pharmacological and nutritional factors to drive such conversion are especially in demand. In the present review, we summarize the current knowledge about the various molecules that can be applied in promoting white‐to‐brown adipose tissue conversion and energy expenditure and the cellular mechanisms involved.     

Polycystic ovary syndrome and adipose tissue

Polycystic ovary syndrome (PCOS) is the most common endocrine metabolic disorder in women of reproductive age. Typically, it is associated with ovulatory dysfunction: dysovulation or anovulation, and symptoms of hyperandrogenism. It incurs risk of metabolic disorders such as diabetes, dyslipidemia and fatty liver. As a key endocrine organ in metabolic homeostasis, adipose tissue is often implicated in these complications. Studies of white adipose tissue (WAT) in PCOS have focused on the mechanism of insulin resistance in this tissue. Clinically, abnormalities in WAT distribution are seen, with decreased waist-to-hip ratio and increased ratio of adipose to lean mass. Such abnormalities are greater when total circulating androgens are elevated. At tissue level, white adipocyte hyperplasia occurs, along with infiltration of macrophages. Secretion of adipokines, cytokines and chemo-attractant proteins is increased in a pro-inflammatory manner, leading to reduced insulin sensitivity via alteration of glucose transporters, and hence decreased glucose uptake. The kinetics of non-esterified fatty acids (or free fatty acids) is also altered, leading to lipotoxicity. In recent years, brown adipose tissue (BAT) has been studied in women with PCOS. Although abundance is low in the body, BAT appears to play a significant role in energy expenditure and metabolic parameters. Both supra-clavicular skin temperature, which reflects BAT activity, and BAT mass are reduced in women with PCOS. Moreover, BAT mass and body mass index (BMI) are inversely correlated in patients. In the adipocyte, increased total circulating androgen levels reduce expression of uncoupling protein 1 (UCP1), a key protein in the brown adipocyte, leading to reduced biogenesis and mitochondrial respiration and hence a reduction in post-prandial thermogenesis. BAT is currently being investigated as a possible new therapeutic application.     

Brown adipose tissue in cancer patients: Possible cause of cancer-induced cachexia

Summary Cachexia is a common manifestation of advanced cancer and frequently contributes to physical disability and mortality. An increased metabolic rate has been suggested to be one of the causes of cancer-induced cachexia, although the mechanisms producing this hypermetabolism remain unclear. The presence and activation of brown adipose tissue, a highly thermogenic tissue, may result in a hypermetabolic state and be partially responsible for weight loss in cancer patients. To investigate this hypothesis, we examined necropsy samples of peri-adrenal tissues using light microscopy to identify the prevalence of brown adipose tissue in 25 cachectic patients who died from cancer and 15 age-matched subjects who died from other illnesses. Brown adipose tissue was observed in 20 of the cancer patients (80%) compared to 2 of the age-matched subjects (13%). Therefore, our preliminary results indicate that a high prevalence of brown adipose tissue is associated with cancer-induced cachexia and may reflect an abnormal mechanism responsible for profound energy expenditure and weight loss.Supported in part by NIH-NHLBI, NRSA, PHS-2271 & HL07338-05     

Non-shivering thermogenesis in brown adipose tissue and aging

The aging-induced decrease in non-shivering thermogenic capacity was prevented in the genetically CCK-A receptor deficient, diabetic obese OLETF rats, provably by an increase in the responsiveness of BAT to glucagon. The potential metabolic capacities can be sustained until aged period.