白色脂肪棕色化的研究进展

随着经济的发展,生活水平的提高,营养状况的改善,伴随能量摄入过剩而导致的肥胖已成为威胁健康的重要问题。肥胖又与心血管疾病密切相关~([1])。减轻和控制体重已成为医疗公共卫生事业亟待研究和解决的问题。人体中分布白色脂肪组织(WAT)和棕色脂肪组织(BAT)2种脂肪组织。WAT以三酰甘油的形式存储人体内摄入的过多能量,BAT则以产生热量的形式消耗体内的能量~([2])。     

白色脂肪棕色化研究进展

以往的观点认为,哺乳动物体内主要存在两种脂肪组织——白色脂肪（WAT）和棕色脂肪（BAT）。WAT的主要功能是以甘油三酯的形式储存能量,而BAT则通过产热来维持机体的能量代谢平衡。近年来,人们在WAT中发现了一种与BAT一样具有产热功能的所谓“米色脂肪”（beigecell）,这种现象也被认为是WAT棕色化。     

肥胖治疗新希望：白色脂肪棕色化

哺乳动物体内有两种脂肪组织,白色脂肪和棕色脂肪。白色脂肪以储存能量为主,棕色脂肪则以消耗能量产热,维持体温恒定。棕色脂肪组织约占体重的2％以下,棕色脂肪细胞富含大量线粒体和解偶联蛋白1（UCP-1）,线粒体产生大量的ATP,通过UCP-1的解偶联作用,转换成热量释放。棕色脂肪细胞也有大量的脂滴,与白色脂肪细胞不同,它们以多房小脂滴形式存在,更方便于被氧化利用。     

棕色脂肪——好脂肪

一说起体内的脂肪组织,您首先想到的是什么呢？白颜色的、肥肥的、让胖人深恶痛绝的一种东西？这其实是我们通常认为的一种脂肪,又叫白色脂肪。因为它分泌的多是炎症因子或其他发挥不利作用的脂肪因子,同时它的增多也是肥胖的一种标志,所以我们通常把它看做是一种坏脂肪（当然,并非说白色脂肪就一无是处,很多时候,我们还需要它来提供能量）。     

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.     

3,5-二碘-L-甲状腺素对白色脂肪棕色化的作用

目的 探究3,5-二碘-L-甲状腺素(T2)诱导白色脂肪棕色化的作用.方法 3T3-LI脂肪前体细胞诱导分化并用油红O染色进行鉴定;细胞分化过程中予不同浓度梯度(1 nmol/L、10 nmol/L、100 nmol/L)的T2处理,待细胞分化成熟后,分别用实时荧光定量PCR、Western印迹检测解耦联蛋白-1(UCP-1)表达水平的变化;仅予高浓度(100 nmol/L) T2处理,Western印迹法检测其他棕色脂肪功能性基因,包括诱导细胞死亡DNA片段化因子α样效应因子A(CIDEA)、过氧化物酶体增殖物活化受体γ协同刺激因子-1α(PGC-1α)蛋白表达变化.结果 3T3-L1脂肪前体细胞呈成纤维细胞样形态,胞浆中无脂滴;诱导分化成熟后光镜下油红O染色可见细胞内大量环状脂滴.在细胞分化过程中予不同浓度T2干预后,分化成熟的脂肪细胞上UCP-1 mRNA水平均有升高(t=3.97、11.77、17.7,P均＜0.05),蛋白表达水平也均有改变(t=13.31、14.55、23.62,P均＜0.05),且在高浓度(100nmoL/L)下最明显.在高浓度T2(100 nmol/L)干预下,成熟脂肪细胞的棕色脂肪其他功能性基因蛋白CIDEA、PGC-1α水平表达增加(t=15.92、17.36,P均＜0.05).结论 T2可诱导由3T3-L1脂肪前体细胞分化而来的成熟白色脂肪细胞表达棕色脂肪功能性基因.     

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.     

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.     

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.     

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.     

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     

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...     

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。     

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,从而为肥胖及其相关疾病的防治提供了新的途径.     

Molecular pathways regulating the formation of brown‐like adipocytes in white adipose tissue

Adipose tissue is functionally composed of brown adipose tissue and white adipose tissue. The unique thermogenic capacity of brown adipose tissue results from expression of uncoupling protein 1 in the mitochondrial inner membrane. On the basis of recent findings that adult humans have functionally active brown adipose tissue, it is now recognized as playing a much more important role in human metabolism than was previously thought. More importantly, brown‐like adipocytes can be recruited in white adipose tissue upon environmental stimulation and pharmacologic treatment, and this change is associated with increased energy expenditure, contributing to a lean and healthy phenotype. Thus, the promotion of brown‐like adipocyte development in white adipose tissue offers novel possibilities for the development of therapeutic strategies to combat obesity and related metabolic diseases. In this review, we summarize recent advances in understanding the molecular mechanisms involved in the recruitment of brown‐like adipocyte in white adipose tissue. Copyright © 2014 John Wiley & Sons, Ltd.