褐色脂肪组织研究的最新进展和科学意义

哺乳动物体内存在着褐色脂肪组织。有别于白色脂肪组织储存能量的功能,褐色脂肪组织的主要功能是通过产热作用来维持机体的能量代谢平衡。陆续有研究阐明调控褐色脂肪组织分化与能量代谢过程的分子机制,逐渐揭示了褐色脂肪组织分化与能量代谢过程中涉及的信号通路与转录调控。这不仅让我们更好地理解褐色脂肪组织在能量代谢调控中的重要作用,而且为基于褐色脂肪组织的肥胖治疗提供了理论依据。本文阐述了近年来研究发现的褐色脂肪组织分化与代谢过程中发挥重要作用的信号通路与转录调控,并讨论了多种基于针对褐色脂肪组织的肥胖治疗手段的有效性与可行性。     

调控褐色脂肪细胞分化的microRNAs

MicroRNA(miRNA)是近年来在真核生物中发现的一类长约22nt的内源性非编码RNA,在动物中主要通过抑制靶mRNA翻译,在转录后水平调控基因表达。动物体内有两种类型的脂肪组织：褐色和白色脂肪,白色脂肪以甘油三脂形式贮存能量,而褐色脂肪利用甘油三酯产生能量。褐色脂肪因其对肥胖的拮抗作用而对研究肥胖等代谢疾病具有重要意义,大量研究表明miRNA在褐色脂肪细胞分化中扮演着重要角色,其自身也受到多种转录因子和环境因子调控,这个复杂的调控网络维持了体内脂肪组织稳态。文章主要综述了miRNA在褐色脂肪细胞分化中的最新研究进展,以期为利用miRNA进行肥胖、糖尿病等相关疾病及其并发症的治疗提供新思路。     

褐色脂肪组织产热及其调节机制

褐色脂肪组织产热受至体内各种生理因素的调节,其线粒体的解偶联蛋白的调节已成为褐色脂肪组织产热调节的关键。交感神经释放的去甲肾上腺素,甲状腺素,Ｔ３和胰岛素等内分泌激素可以从基因表达水平影响到解偶联蛋白的含量,从而调节褐色脂肪组织的产热能力。     

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.     

冷暴露对中缅树鼩褐色脂肪组织中解偶联蛋白1含量的影响

自备抗血清采用酶联免疫法测定了中缅树鼩(Tupaia belangeri)在(5±1)℃冷暴露0 d、7 d、14 d、21d、28 d时,褐色脂肪组织(BAT)中解偶联蛋白1(UCP1)的含量.结果表明,随着冷暴露时间的延长,中缅树鼩的体重、褐色脂肪组织重量均表现出了增加的趋势,BAT线粒体总蛋白和UCP1的含量也呈增加的趋势,其中UCP1的含量在28 d时达到极显著水平,比对照组增加了55.9%.说明冷暴露能够诱导中缅树鼩UCP1表达增加,从而使其适应性产热增加.     

生理节律及其应用

生理节律(Biorhm program)也叫生理节奏。普遍存在于生物界的各生命过程中,是生物体内存在的一种基本生理现象。不论是单细胞还是多细胞的有机体、动物、植物、人体组织、器官和整体的生理功能,均有周期性节律活动,这种生物体内存在的节律也称“生物钟”。人类     

冷驯化条件下中缅树鼩脂肪组织代谢产物的变化

为探究冷驯化条件下中缅树鼩(Tupaia belangeri)白色脂肪组织(WAT)和褐色脂肪组织(BAT)的差异代谢物变化,本研究采集对照组和冷驯化28天组中缅树鼩的WAT和BAT,采用非靶向代谢组液相色谱—质谱联用检测技术分析其差异代谢物含量变化.结果 表明,冷驯化组较对照组WAT中有7种差异代谢物显著上调;BAT...     

环境致癌物与病毒协同致癌作用的研究进展

癌症是威胁人类健康的重大疾病,其发病与环境、病原体、遗传和生活方式等多种因素有关。环境致癌物是诱发癌症的重要因素之一,如多环芳烃、亚硝胺和霉菌毒素等均为环境中广泛存在的典型致癌物,它们在体内经过代谢活化后导致DNA损伤最终诱发癌症。病毒感染也是人类癌症发病的重要原因,如乙肝病毒(HBV)和丙肝病毒(HCV)能够诱发肝癌;EB病毒(EBV)在鼻咽癌的发生过程中起关键作用;人乳头瘤病毒(HPV)与宫颈癌和食管癌有关。然而,由于癌症发病机制复杂,仅考虑单一因素往往难以进行合理的解释。因此,明确不同致癌因素之间的协同作用对于揭示致癌作用机制具有重要意义。本文综述了近年来有关环境致癌物与病毒协同致癌作用的研究,以期为深入阐明肿瘤发生和发展的作用机制找到新的突破口,进而为相关癌症的防治提供新策略。     

DHA对高脂食物诱导体重增加的保护作用的研究

目的为了探索DHA抑制高脂食物诱导的脂肪增加的机制。方法本研究通过给C57BL/6小鼠饲喂普通食物(C57BL/6 C组),45%高脂食物(C57BL/6 H组)以及45%高脂食物加DHA(每克食物0. 2 g的DHA)(FAD3 C组)和(每克食物0. 4 g的DHA)(FAD3 H组),20周。第19周测定静止代谢率,20周处死动物检测血清瘦素、甘油三酯的浓度,以及白色脂肪组织和褐色脂肪组织中脂肪分化因子和褐色基因的表达。结果研究发现高脂食物导致C57BL/6 H组的体重、体脂、瘦素和甘油三酯最高(P0. 05)。与C57BL/6 H组相比,DHA降低了体重、体脂、瘦素和甘油三酯(P0. 05),并且有剂量依赖性。在白色脂肪中,DHA降低了高脂食物诱导的PPARγ、CEBPα和SREP1c mRNA表达的增加(P0. 05)。与对照组相比,DHA显著增加白色脂肪组织和褐色脂肪组织中脂肪褐色化基因PGC1αmRNA和UCP1 mRNA表达(P0. 05)。结论食物补充DHA通过增加产热基因的表达,增加静止代谢率、降低白色脂肪和褐色脂肪的脂肪分化基因的表达,从而降低高脂食物诱导的体重增加。     

美研制出新成像技术帮助检测癌症

美国宾夕法尼亚大学研究人员最近将计算机轴向断层扫描技术（CAT）和正电子发射断层显像技术（PET）相结合,研制出了一种新的成像技术,采用新技术可以更准确地检测癌症等疾病。     

Anatomical and functional assessment of brown adipose tissue by magnetic resonance imaging

Brown adipose tissue (BAT) is the primary tissue responsible for nonshivering thermogenesis in mammals. The amount of BAT and its level of activation help regulate the utilization of excessive calories for thermogenesis as opposed to storage in white adipose tissue (WAT) which would lead to weight gain. Over the past several years, BAT activity in vivo has been primarily assessed by positron emission tomography-computed tomography (PET-CT) scan using 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) to measure glucose utilization associated with BAT mitochondrial respiration. In this study, we demonstrate the feasibility of mapping and estimating BAT volume and metabolic function in vivo in rats at a 9.4T magnetic resonance imaging (MRI) scanner using sequences available from clinical MR scanners. Based on the morphological characteristics of BAT, we measured the volume distribution of BAT with MRI sequences that have strong fat-water contrast. We also investigated BAT volume by utilizing spin-echo MRI sequences. The in vivo MRI-estimated BAT volumes were correlated with direct measurement of BAT mass from dissected samples. Using MRI, we also were able to map hemodynamic responses to changes in BAT metabolism induced pharmacologically by β3-adrenergic receptor agonist, CL-316,243 and compare this to BAT activity in response to CL-316,243 assessed by PET 18F-FDG. In conclusion, we demonstrate the feasibility of measuring BAT volume and function in vivo using routine MRI sequences. The MRI measurement of BAT volume is consistent with quantitative measurement of the tissue ex vivo.     

Glycerokinase activity in human brown adipose tissue

Brown adipose tissue (BAT) is known to be responsible for heat production in newborn and adult hibernating mammals. In rats and mice, BAT has been demonstrated to possess a much higher glycerokinase activity than white adipose tissue (WAT). It has been speculated that this high activity may cause the futile cycle of triglyceride breakdown and resynthesis to be activated, thus contributing to heat production. However, at present very little information is available regarding the location, function, and quantitative importance of BAT in adult human subjects. Our objective in this study was to locate BAT in human subjects and to characterize it biochemically, especially with respect to the enzyme glycerokinase. We have looked for histologically identifiable BAT in 32 human subjects and found it in 12 subjects. Most of the BAT samples were obtained from perirenal adipose depots in children undergoing surgery. Some of the samples were almost totally comprised of BAT cells, whereas others were a mixture of BAT cells and WAT cells. The glycerokinase activity per gram of tissue was higher in BAT than in WAT in all the subjects where the above comparison was made. The activity per mg protein or per microgram DNA was higher in most BAT samples. In one pure BAT specimen, the basal lipolytic rate and the lipoprotein lipase activity were measured and they were both higher in BAT than in the WAT obtained from the same patient. These results show that human brown adipose tissue possesses an enzymatic profile very similar to that of rodent brown adipose tissue.     

Human Brown Adipose Tissue Depots Automatically Segmented by Positron Emission Tomography/Computed Tomography and Registered Magnetic Resonance Images

Reliably differentiating brown adipose tissue (BAT) from other tissues using a non-invasive imaging method is an important step toward studying BAT in humans. Detecting BAT is typically confirmed by the uptake of the injected radioactive tracer ¹⁸F-Fluorodeoxyglucose (¹⁸F-FDG) into adipose tissue depots, as measured by positron emission tomography/computed tomography (PET-CT) scans after exposing the subject to cold stimulus. Fat-water separated magnetic resonance imaging (MRI) has the ability to distinguish BAT without the use of a radioactive tracer. To date, MRI of BAT in adult humans has not been co-registered with cold-activated PET-CT. Therefore, this protocol uses ¹⁸F-FDG PET-CT scans to automatically generate a BAT mask, which is then applied to co-registered MRI scans of the same subject. This approach enables measurement of quantitative MRI properties of BAT without manual segmentation. BAT masks are created from two PET-CT scans: after exposure for 2 hr to either thermoneutral (TN) (24 °C) or cold-activated (CA) (17 °C) conditions. The TN and CA PET-CT scans are registered, and the PET standardized uptake and CT Hounsfield values are used to create a mask containing only BAT. CA and TN MRI scans are also acquired on the same subject and registered to the PET-CT scans in order to establish quantitative MRI properties within the automatically defined BAT mask. An advantage of this approach is that the segmentation is completely automated and is based on widely accepted methods for identification of activated BAT (PET-CT). The quantitative MRI properties of BAT established using this protocol can serve as the basis for an MRI-only BAT examination that avoids the radiation associated with PET-CT.     

Is It Possible to Detect Activated Brown Adipose Tissue in Humans Using Single-Time-Point Infrared Thermography under Thermoneutral Conditions? Impact of BMI and Subcutaneous Adipose Tissue Thickness

Purpose

To evaluate the feasibility to detect activated brown adipose tissue (BAT) using single-time-point infrared thermography of the supraclavicular skin region under thermoneutral conditions. To this end, infrared thermography was compared with 18-F-FDG PET, the current reference standard for the detection of activated BAT.

Methods

120 patients were enrolled in this study. After exclusion of 18 patients, 102 patients (44 female, 58 male, mean age 58±17 years) were included for final analysis. All patients underwent a clinically indicated 18F-FDG-PET/CT examination. Immediately prior to tracer injection skin temperatures of the supraclavicular, presternal and jugular regions were measured using spatially resolved infrared thermography at room temperature. The presence of activated BAT was determined in PET by typical FDG uptake within the supraclavicular adipose tissue compartments. Local thickness of supraclavicular subcutaneous adipose tissue (SCAT) was measured on CT. Measured skin temperatures were statistically correlated with the presence of activated BAT and anthropometric data.

Results

Activated BAT was detected in 9 of 102 patients (8.8%). Local skin temperature of the supraclavicular region was significantly higher in individuals with active BAT compared to individuals without active BAT. However, after statistical correction for the influence of BMI, no predictive value of activated BAT on skin temperature of the supraclavicular region could be observed. Supraclavicular skin temperature was significantly negatively correlated with supraclavicular SCAT thickness.

Conclusion

We conclude that supraclavicular SCAT thickness influences supraclavicular skin temperature and thus makes a specific detection of activated BAT using single-time-point thermography difficult. Further studies are necessary to evaluate the possibility of BAT detection using alternative thermographic methods, e.g. dynamic thermography or MR-based thermometry taking into account BMI as a confounding factor.     

Cold-induced activation of brown adipose tissue and adipose angiogenesis in mice

Exposure of humans and rodents to cold activates thermogenic activity in brown adipose tissue (BAT). This protocol describes a mouse model to study the activation of BAT and angiogenesis in adipose tissues by cold acclimation. After a 1-week exposure to 4 °C, adult C57BL/6 mice show an obvious transition from subcutaneous white adipose tissue (WAT) into brown-like adipose tissue (BRITE). The BRITE phenotype persists after continuous cold exposure, and by the end of week 5 BRITE contains a high number of uncoupling protein-1-positive mitochondria, a characteristic feature of BAT. During the transition from WAT into BRITE, the vascular density is markedly increased owing to the activation of angiogenesis. In BAT, cold exposure stimulates thermogenesis by increasing the mitochondrial content and metabolic rate. BAT and the increased metabolic rate result in a lean phenotype. This protocol provides an outstanding opportunity to study the molecular mechanisms that control adipose mass.     

Effects of exercise on brown and beige adipocytes

Physical exercise leads to beneficial effects in numerous tissues and organ systems and offers protection against obesity and type 2 diabetes. Recent studies have investigated the role of exercise on brown adipose tissue (BAT) and white adipose tissue (WAT), and have indicated marked adaptations to each tissue with exercise. Studies investigating the effects of exercise on BAT have produced conflicting results, with some showing an increase in the thermogenic activity of BAT and some demonstrating a decrease in the thermogenic activity of BAT. Human studies have observed a down-regulation of BAT activity (measured by a reduction in glucose uptake) in response to exercise. In WAT, exercise decreases adipocyte size, alters gene expression, and increases mitochondrial activity. Transplantation of exercise-trained subcutaneous WAT (scWAT) improves whole-body metabolic health. In rodents, exercise also results in a beiging of scWAT. Thus, exercise-induced changes to adipose tissue may be part of the mechanism by which exercise improves metabolic health.     

Brown and beige fat: From molecules to physiology

The recent re-discovery of brown adipose tissue (BAT) and even more recent discovery of the browning of white adipose tissue (WAT) in humans have generated intense scientific interest in the role of adipose tissue as potential target against obesity and its metabolic complications. The purpose of this review is to: i) critically evaluate the current evidence on the physiological significance of BAT and the browning of WAT in metabolic function in humans and ii) discuss factors that have been reported to regulate BAT and/or the browning of WAT in humans. The current literature supports that BAT and the browning of WAT constitute promising emerging targets for interventions aiming to prevent and/or treat of obesity and its metabolic complications. Further research is needed to better understand the physiological significance of BAT and browning of WAT in health and disease along with the factors modulating their metabolic function in humans.     

Localized proton magnetic resonance spectroscopy of lipids in adipose tissue at high spatial resolution in mice in vivo

We describe a localized proton magnetic resonance spectroscopy ((1)H-MRS) method for in vivo measurement of lipid composition in very small voxels (1.5 mm x 1.5 mm x 1.5 mm) in adipose tissue in mice. The method uses localized point-resolved spectroscopy to collect (1)H spectra from voxels in intra-abdominal white adipose tissue (WAT) and brown adipose tissue (BAT) deposits. Nonlinear least-squares fits of the spectra in the frequency domain allow for accurate calculation of the relative amount of saturated, monounsaturated, and polyunsaturated fatty acids. All spectral data are corrected for spin-spin relaxation. The data show BAT of NMRI mice to be significantly different from BAT of NMRI nu/nu mice in all aspects except for the fraction of monounsaturated fatty acids (FM); for WAT, only the FM is different. BAT and WAT of NMRI mice differ in the amount of saturated and di-unsaturated fatty acids. This method provides a potential tool for studying lipid metabolism in small animal models of disease during the initiation, progression, and manifestation of obesity-related disorders in vivo. Our results clearly demonstrate that localized (1)H-MRS of adipose tissue in vivo is possible at high spatial resolution with voxel sizes down to 3.4 ml.     

Adiposity-Related Cancer and Functional Imaging of Brown Adipose Tissue

Objective: Brown adipose tissue (BAT) is involved in energy dissipation and cytokine production and is potentially beneficial for the human body. The aim of the paper is to review the literature on adiposity-related cancer and functional imaging of BAT.Methods: We performed a review on adiposity-related cancer and functional imaging of BAT. We extensively researched papers for information on BAT molecular biology, as well as functional imaging modalities.Results: Adipose tissue is linked to the development of many cancers. Multiple drugs including fenofibrate, spironolactone, and other substances, as well as experimental agents like β-3 receptor agonists, caffeine, green tea extract, medium chain triglycerides (MCTs), and adenosine are known to stimulate and activate BAT. However, cold and nonshivering thermogenesis are the main activators of BAT. BAT has been detected on both magnetic resonance imaging (MRI) and 18F-fluorodexoxyglucose positron emission tomography (18F-FDG-PET)-based imaging in multiple studies. Different methods of cold stimulation and static and dynamic protocols have been used to detect and image BAT. Factors like sex, fasting or fed state, surface skin temperature, and/or body mass index (BMI) may influence PET-based BAT detection. BAT has also been detected using MRI, ^99mTechnetium(Tc)-sestamibi, and 123I- metaiodobenzylguanidine single-photon emission computed tomography/computed tomography (MIBG SPECT/CT).Conclusions: Stimulation of BAT offers promise in the management of obesity-related conditions. Tracers like [¹⁵O]-H₂O, [¹¹C] acetate, and 18F-fluoro-6-thia-heptadecanoic acid (18F-FTHA) that measure BAT blood flow, oxygen utilization, and nonessential fatty acid (NEFA) uptake, respectively, have been studied in humans. Future studies should focus on BAT tissue generation by altering the genetic pathways of adiposity-linked genes.Abbreviations: BAT = brown adipose tissue BMI = body mass index CT = computed tomography 18F-FDG = 18F-fluorodexoxyglucose 18F-FTHA = 18F-fluoro-6- thia-heptadecanoic acid GLUT = glucose transporter MIBG = metaiodobenzylguanidine MRI = magnetic resonance imaging PET = positron emission tomography PPAR = peroxisome proliferator-activated receptor SPECT = single-photon emission computed tomography SUV = standard uptake value Tc = technetium UCP-1 = uncoupling protein 1 WAT = white adipose tissue