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.     

棕色脂肪基础研究进展

哺乳动物体内的脂肪组织按功能主要分为白色脂肪组织（WAT）和棕色脂肪组织（BAT）。WAT主要以甘油三酯的形式储存机体摄取的能量，当能量摄入超出脂肪细胞的存储能力时，机体就会产生肥胖。与WAT不同，BAT主要通过氧化脂肪酸消耗能量。BAT一方面通过非颤抖性产热维持动物体温，另一方面可以消耗机体过剩的能量，维持能量平衡。基于BAT在消耗能量方面的作用，     

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。     

脂蛋白脂酶的组织特异性表达及其调节

目前研究表明 ,白色脂肪组织 (WAT)、棕色脂肪组织 (BAT)、骨骼肌及心肌的脂蛋白脂酶 (LPL)在机体的脂质代谢中的作用各不相同 ,而各种影响因素对LPL的作用又表现出组织特异性。如胰岛素可刺激脂肪组织的LPL ,而儿茶酚胺在抑制WAT的LPL活性的同时可刺激骨骼肌、心肌及BAT的LPL。烟碱可增加心肌的LPL而饮酒可增加BAT的LPL活性 ,体育锻炼和生长激素可增加骨骼肌LPL活性。这些研究提示 ,有可能通过调节LPL的组织特异性表达以达到使机体肥胖或消瘦的目的     

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])。     

长链非编码RNAs与脂肪组织的关系

长链非编码RNAs(lncRNAs)是长度大于200个核苷酸而无蛋白编码能力的功能性RNA分子.近年来研究表明,lncRNAs可通过各种机制调控脂肪组织分化形成、功能结构维持及促进白色脂肪组织(WAT)棕色化,特别是对棕色脂肪组织(BAT)的分化成熟发挥重要作用.同时,lncRNAs与肥胖及代谢性疾病的发生、发展密切联系.     

敲低GPM6B促进白色脂肪细胞向棕色脂肪表型转变

目的 研究糖蛋白M6B(GlycoproteinM6B,GPM6B)在白色脂肪细胞向棕色脂肪表型转变中的作用.方法 ①Western blot和qPCR检测小鼠白色脂肪组织(white adipose tissue,WAT)和棕色脂肪组织(brown adipose tissue,BAT)中GPM6B的表达.②分别用对...     

棕色脂肪临床研究进展

棕色脂肪组织（BAT）被证明存在于正常成人体内,它的结构与功能有别于白色脂肪组织（WAT）,但二者均参与机体的物质和能量代谢。有证据表明BAT或WAT的功能失衡在肥胖症等代谢性疾病的发生发展中起一定作用。目前肥胖及其相关代谢性疾病的患病率逐年升高,日益加重国家卫生经济负担,已成为21世纪人类面临的最严峻的公共卫生危机之一,且缺乏有效的防治手段。对棕色脂肪的深入研究,有望为肥胖等代谢性疾病的防治提供新的思路和手段。     

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.     

Response of adipose tissue to early infection with Trypanosoma cruzi (Brazil strain)

Brown adipose tissue (BAT) and white adipose tissue (WAT) and adipocytes are targets of Trypanosoma cruzi infection. Adipose tissue obtained from CD-1 mice 15 days after infection, an early stage of infection revealed a high parasite load. There was a significant increase in macrophages in infected adipose tissue and a reduction in lipid accumulation, adipocyte size, and fat mass and increased expression of lipolytic enzymes. Infection increased levels of Toll-like receptor (TLR) 4 and TLR9 and in the expression of components of the mitogen-activated protein kinase pathway. Protein and messenger RNA (mRNA) levels of peroxisome proliferator-activated receptor γ were increased in WAT, whereas protein and mRNA levels of adiponectin were significantly reduced in BAT and WAT. The mRNA levels of cytokines, chemokines, and their receptors were increased. Nuclear Factor Kappa B levels were increased in BAT, whereas Iκκ-γ levels increased in WAT. Adipose tissue is an early target of T. cruzi infection.     

Acute and chronic regulation of ob mRNA levels by beta3-adrenoceptor agonists in obese Yellow KK mice.

The inhibitory effect of beta3-adrenoceptor agonists on the ob gene in brown adipose tissue (BAT) and white adipose tissue (WAT) is now well documented both in vivo in lean animals and in vitro, but the reported effects of beta3-adrenoceptor agonists on ob gene expression in obese animals remain controversial. We investigated whether ob gene expression in BAT and WAT is reduced by acute and chronic administrations of a beta3-adrenoceptor agonist, CL316,243 (CL). The ob gene mRNA levels in BAT, perimetric and inguinal WAT of obese Yellow KK mice were about 4-fold higher than those of lean controls. Acute exposure (6 h) to CL decreased ob gene mRNA levels in three fat depots in both animals. Chronic exposure (10 days) to CL also decreased ob gene mRNA levels in BAT, perimetric, and inguinal WAT in both animals. We concluded that acute and chronic regulation by a beta3-adrenoceptor agonist suppressed ob gene expression in obese Yellow KK mice and lean controls.     

MR signal-fat-fraction analysis and T2* weighted imaging measure BAT reliably on humans without cold exposure

ObjectiveBrown adipose tissue (BAT) is compositionally distinct from white adipose tissue (WAT) in terms of triglyceride and water content. In adult humans, the most significant BAT depot is localized in the supraclavicular area. Our aim is to differentiate brown adipose tissue from white adipose tissue using fat T2* relaxation time mapping and signal-fat-fraction (SFF) analysis based on a commercially available modified 2-point-Dixon (mDixon) water–fat separation method. We hypothesize that magnetic resonance (MR) imaging can reliably measure BAT regardless of the cold-induced metabolic activation, with BAT having a significantly higher water and iron content compared to WAT.Material and methodsThe supraclavicular area of 13 volunteers was studied on 3 T PET–MRI scanner using T2* relaxation time and SFF mapping both during cold exposure and at ambient temperature; and ¹⁸F-FDG PET during cold exposure. Volumes of interest (VOIs) were defined semiautomatically in the supraclavicular fat depot, subcutaneous WAT and muscle.ResultsThe supraclavicular fat depot (assumed to contain BAT) had a significantly lower SFF and fat T2* relaxation time compared to subcutaneous WAT. Cold exposure did not significantly affect MR-based measurements. SFF and T2* values measured during cold exposure and at ambient temperature correlated inversely with the glucose uptake measured by ¹⁸F-FDG PET.ConclusionsHuman BAT can be reliably and safely assessed using MRI without cold activation and PET-related radiation exposure.     

Fasting-induced adipose factor identified as a key adipokine that is up-regulated in white adipose tissue during pregnancy and lactation in the rat

Adipokines, which are expressed and secreted from white adipose tissue (WAT), are potential factors that could contribute to the changes in energy homeostasis that occurs in pregnancy and lactation to meet the nutrient demands of fetal growth and milk production. The aim was to identify adipokines that could be involved by measuring the pattern of their mRNA expression in adipose tissue. Adipokine mRNAs were measured by quantitative RT-PCR in RNA isolated from white and brown adipose tissue (BAT) of rats at days 7, 14 and 21 of pregnancy, day 7 of lactation and virgin at dioestrus phase. The results for leptin, adiponectin and resistin expression in WAT essentially confirmed previous studies and it is unlikely that they are directly involved in the metabolic adaptations. The relative amounts of the mRNAs of the adipokines in BAT were comparable with those in WAT, but the patterns of expression did not follow those in WAT, except for apelin. Visfatin mRNA in WAT was elevated 2.5-fold only at day 21 of pregnancy. Apelin mRNA in WAT was increased 2.2-fold at day 7 of pregnancy. Retinol-binding protein 4 mRNA in WAT decreased to 46% of control at day 14 of pregnancy. Fasting-induced adipose factor (FIAF) mRNA in WAT was 2.2- to 2.5-fold higher throughout pregnancy and lactation. The marked induction of FIAF identifies this adipokine as a potential regulator of the metabolic adaptations that occur during pregnancy and lactation.     

Resistance to obesity by repression of VEGF gene expression through induction of brown-like adipocyte differentiation

Adipose tissues are classified into white adipose tissue (WAT) and brown adipose tissue (BAT). WAT is responsible for energy storage, and malfunction is associated with obesity. BAT, on the contrary, consumes fat to generate heat through uncoupling mitochondrial respiration and is important in body weight control. Vascular endothelial growth factor (VEGF)-A is the founding member of the VEGF family and has been found highly expressed in adipose tissue. A genetic mouse model of an inducible VEGF (VEGF-A) repression system was used to study VEGF-regulated energy metabolism in WAT. VEGF-repressed mice demonstrated lower food efficiency, lower body weight, and resistance to high-fat diet-induced obesity. Repression of VEGF expression caused morphological and molecular changes in adipose tissues. VEGF repression induced brown-like adipocyte development in WAT, up-regulation of BAT-specific genes including PRDM16, GATA-1, BMP-7, CIDEA, and UCP-1 and down-regulation of leptin, a WAT-specific gene. VEGF repression up-regulated expression of VEGF-B and its downstream fatty acid transport proteins. Relative levels of VEGF/VEGF-B may be important switches in energy metabolism and of pharmaceutical significances.     

The role of estrogen and estrogen receptor-alpha in male adipose tissue

Males and females both express estrogen receptor (ER) in white adipose tissue (WAT), and estrogens appear to play an important role in regulating WAT in females. However, the role of ER in male WAT was unclear. In this review, we describe our work, which used wild type (WT) and ERalpha-knockout (alphaERKO) male and female mice to determine the role of ERalpha in regulating WAT and brown adipose tissue (BAT). There were progressive increases in WAT with advancing age in alphaERKO compared with WT males; weights of various WAT depots in alphaERKO males were increased by more than 100% compared with WT controls during adulthood. Conversely, BAT weight was similar in alphaERKO and WT males at all ages. Adipocyte areas and numbers were also increased in WAT from alphaERKO compared with WT males. Compared with WT controls, alphaERKO females also had increases in WAT. The alphaERKO mice also had insulin resistance and impaired glucose tolerance, similar to humans lacking ERalpha or aromatase. The obesity in alphaERKO males appeared to involve decreased energy expenditure rather than hyperphagia. In summary, ERalpha absence causes adipocyte hyperplasia and hypertrophy in WAT, but not BAT, and is accompanied by insulin resistance and glucose intolerance in both males and females. These results are the first evidence that the estrogen/ERalpha signaling system is critical in female and male WAT deposition, and may have clinical implications.     

Expression of peroxisome proliferator-activated receptors in lean and obese Zucker rats

OBJECTIVE: Examination of the pattern of expression of peroxisome proliferator-activated receptor (PPAR) isoforms alpha and gamma in a model of obesity. DESIGN: Examination of adipose tissue and primary adipocyte cultures from lean and obese Zucker rats at different ages (28 days and 12 weeks). METHODS: mRNA levels were measured by RNase protection assay.RESULTS: The highest levels of PPARalpha and gamma mRNA were present in brown adipose tissue (BAT), followed by liver and white adipose tissue (WAT) for the alpha and gamma subtypes, respectively, at both ages examined. PPARalpha was expressed 100-fold higher in BAT compared with WAT, and PPARgamma mRNA levels were 2-fold higher in the WAT of obese compared with lean rats. PPARalpha and gamma expression was minimal in m. soleus, although higher levels of PPARgamma were found in the diaphragm. In marked contrast to the findings in vivo, virtually no PPARalpha mRNA could be detected in BAT cultures differentiated in vitro. CONCLUSION: PPARalpha and gamma are most highly expressed in BAT in vivo. However, PPARalpha is undetectable in brown adipose cells in vitro, suggesting that the expression of this receptor is induced by some external stimuli. In addition, the expression of PPARgamma was increased in WAT from young obese animals, compatible with an early adaptive phenomenon. Finally, the presence of PPARgamma mRNA is detectable only in particular muscles, such as the diaphragm, suggesting the possibility of an influence of fiber type on its expression, although exercise did not influence the expression of PPARgamma in other skeletal muscles.     

Effect of oral oleoyl-estrone on adipose tissue composition in male rats

OBJECTIVE: To determine whether the oral administration of oleoyl-estrone has similar mass-decreasing effects on the main different sites of white adipose tissue (WAT). DESIGN: Adult male Zucker lean rats were given a daily oral gavage of oleoyl-estrone (OE, 10 micromol/kg) in 0.2 ml of sunflower oil for 10 days, and were compared with controls receiving only the oil. The mass of the main WAT sites: subcutaneous, epididymal, mesenteric, retroperitoneal, gluteal, perirenal and interscapular, as well as perirenal and interscapular brown adipose tissue (BAT), were dissected and studied. MEASUREMENTS: The tissue weight, DNA, protein, lipid and total cholesterol content, together with the levels of leptin and acyl-estrone in the larger WAT and BAT masses, were measured. RESULTS: The weights of WAT depots were correlated with body weight but those of BAT were not. Cell size was maximal for epididymal and mesenteric and minimal for subcutaneous and retroperitoneal WAT and BAT. Differences were detected in DNA, and in protein and lipid content between distinct WAT sites. OE treatment tended to decrease cell number and cell size in WAT; only small differences in composition were found between WAT locations inside the visceral cavity and those outside. Decreases in lipid content were maximal in mesenteric fat. Leptin and acyl-estrone content were fairly uniform at the different WAT sites, except for high concentrations in gluteal WAT. OE induced a greater decrease in leptin and acyl-estrone than in DNA and lipids; changes in these hormones were fairly parallel in all sites. CONCLUSIONS: In general, the differences in composition between visceral and peripheral subcutaneous WAT and their responses to OE were less marked than the individual differences observed between specific sites, regardless of location. WAT sites are fairly diverse in composition, but their response to OE treatment was uniform. OE decreased the weight of WAT through reduction of both cell numbers and size; but did not change the mass or composition of BAT significantly. The effects of OE are more marked in the hormonal signals (leptin and acyl-estrone) from the tissue than in its composition and mass.