花粉对谷氨酸钠所致小鼠肥胖的预防作用

初生乳鼠自出生当天起皮下注射谷氨酸钠2mg/g,连续5天,可复制成小鼠肥胖模型,表现为至6周龄后可发生进行性肥胖。自4周龄断乳后(即肥胖发生前)开始灌喂花粉5～10g/kg,连续30天,对小鼠肥胖有明显的预防作用。花粉预防组的体重和肥胖指数(Lee's Index)明显低于不用花粉的致肥组,并能显著降低血清和肝脏胆固醇与甘油三酯及体内脂肪含量。本文结果提示花粉可能有益于肥胖症的预防,值得临床试用。     

胰岛β细胞Metrnl基因敲除小鼠的鉴定及初步表型分析

目的：基于Cre-LoxP重组酶系统,构建胰岛β细胞Metrnl基因敲除小鼠(Metrnl-KO),为进一步探究Metrnl基因在糖尿病疾病中的发病机制提供动物模型。方法：将雌雄基因型均为Metrnl^floxp/+的小鼠合笼杂交,筛选出基因型为Metrnl^floxp/floxp的小鼠,将该基因型小鼠与胰岛β细胞特异性表达Cre重组酶(Ins-2)工具鼠进行杂交繁育,获得基因型为Metrnl^floxp/+;Cre+的小鼠;再将Metrnl^floxp/+;Cre+小鼠与Metrnl^floxp/floxp小鼠杂交获得Metrnl^{floxp/floxp;Cre+}小鼠,基因型为Metrnl^{floxp/floxp;Cre+}的小鼠即为目的鼠。采用RT-q PCR检测Metrnl和胰岛素(Ins-1和Ins-2)的m RNA水平;免疫组化和免疫荧光染色观察胰岛组织Metrnl和胰岛素的蛋白表达情况;记录小鼠体重,同时测定小鼠糖耐量和胰岛素耐量。结果：...     

高脂饮食诱导肥胖小鼠白色脂肪组织中IL-33的表达及意义

目的:探讨细胞因子IL-33在高脂饮食诱导的肥胖小鼠体内不同类型白色脂肪组织的表达情况.方法:3T3-L1前脂肪细胞诱导分化10 d,ELISA检测细胞培养上清中IL-33的含量;Western blot和RT-PCR检测细胞中IL-33的表达.6～8周的C57BL/6雄性小鼠随机分为两组,高脂组给予60％高脂饲料饲养...     

高脂饮食肥胖模型小鼠脂肪组织受体相互作用蛋白140基因的表达

背景：受体相互作用蛋白140基因敲除小鼠可通过增加线粒体生物功能、脂肪酸氧化、氧化磷酸化等代谢途径来抵抗高脂饮食诱导的肥胖。 目的：构建高脂饮食致肥胖模型小鼠,观察脂肪组织受体相互作用蛋白140 mRNA表达水平变化及胰岛素抵抗的关系。 方法：将C57BL/6J雄性小鼠随机分为对照组和高脂饮食组,分别喂养14周后,测量2组小鼠体质量,选取高脂饮食组中体质量大于对照组小鼠平均体质量20%的小鼠作为肥胖组小鼠。 结果与结论：高脂饮食组小鼠中有12只符合标准计入肥胖组。肥胖组小鼠三酰甘油、总胆固醇、空腹血糖、空腹胰岛素水平和胰岛素抵抗指数均明显高于对照组(P < 0.05或P < 0.01);肥胖组小鼠脂肪组织中受体相互作用蛋白140 mRNA的表达高于对照组(P < 0.05);且小鼠脂肪组织受体相互作用蛋白140 mRNA表达水平与三酰甘油水平、胰岛素抵抗指数呈正相关(r=0.526,P < 0.05;r=0.465,P < 0.05),而与总胆固醇、空腹血糖、空腹胰岛素水平无相关性(P > 0.05)。 中国组织工程研究杂志出版内容重点：肾移植;肝移植;移植;心脏移植;组织移植;皮肤移植;皮瓣移植;血管移植;器官移植;组织工程全文链接：     

分泌蛋白Metrnl在不同疾病中作用的研究进展

镍纹样蛋白(Metrnl)是一种与神经营养因子Meteorin同源的新的细胞因子,也是一种分泌蛋白,其基因及产物表现为低组织特异性,在体内广泛表达。该蛋白可类似神经营养因子、脂肪因子、炎性因子及肌肉因子,在机体神经发育、免疫炎性反应、代谢等多方面发挥作用。     

高脂诱导肥胖小鼠视网膜变性的形态学改变

目的 探讨高脂饮食建立的C57BL/6小鼠肥胖模型的视网膜变性的超微结构改变.方法 高脂饲料喂养19周后,小鼠分为肥胖抵抗(DIO-R)组和肥胖倾向(DIO)组,同时对照组小鼠给予基础饲料喂养.应用光镜,透射电镜及TUNEL法检测三组小鼠视网膜超微结构的改变及凋亡情况.结果 与对照组及DIO-R组比较,DIO组小鼠视网...     

无菌小鼠在肠道菌群研究中的应用概述

人类胃肠道中有10～100万亿微生物,这些微生物归属于9个细菌门,其中厚壁菌门和拟杆菌门微生物占了绝大多数[1-3].近年来,越来越多的研究证实,肠道菌群与肥胖相关疾病、心血管疾病、代谢性疾病、肝病、炎症性肠病和结直肠癌存在联系,并在调节胰岛素敏感性、脂肪储存和体重方面发挥关键作用[4-8].在人体中,与基因相比,肠道...     

Nanog蛋白在CD73+小鼠脂肪源间充质干细胞中的表达

目的 探讨Nanog蛋白在小鼠脂肪源间充质干细胞(ADMSCs)中的表达规律.方法 体外分离培养ADMSCs,利用流式细胞仪从ADMSCs中分选出CD73+和CD73 -两个细胞亚群.体外分别培养两组细胞,用免疫细胞化学和免疫荧光测定两组细胞Nanog蛋白的表达,并比较其差异.结果 CD73+ ADMSCs细胞约占总细胞的5％,形态上分为大细胞和小细胞.Nanog蛋白在CD73+ ADMSCs细胞中强阳性表达率(16.85±6.83)％,弱阳性表达率(81.78 ±7.19)％,阴性表达率(1.63±3.59)％;nanog蛋白在CD73 - ADMSCs细胞中强阳性表达率(5.74±2.79)％,弱阳性表达率(85.84 +37.31)％,阴性表达率(8.42±4.12)％.在Nanog阳性表达的细胞中可见不同分裂时相的有丝分裂细胞,CD73+细胞的分裂象明显多于CD73 -细胞.结论 CD73和Nanog可能均是ADMSCs特异性表达的标志,Nanog蛋白强阳性的细胞可能更具幼稚性.通常采用分离培养方法获得的ADMSCs是多种细胞的复合物.     

肥胖小鼠脂肪组织中炎症因子的表达

目的 探讨肥胖对小鼠脂肪中炎症因子分泌的影响及其作用的分子机制。方法 随机选取20只Lepob/ob肥胖小鼠作为研究对象,同窝野生型C57BL/6 J小鼠作为对照组。测定小鼠体重、脂肪重量、血糖、葡萄糖耐量和胰岛素耐量;HE染色观察白色和褐色脂肪细胞的状态,并对脂肪细胞直径进行统计学分析;Western blotting检测诱导型一氧化氮合酶(iNOS)、核因子κB（NF-κB）、蛋白激酶B（Akt）和p-Akt的蛋白表达;Real-time PCR分析白色和褐色脂肪中CC-趋化因子配体2(CCL2)、CD44、集落刺激因子2(CSF2)、胶质纤维酸性蛋白（GFAP）、Iba1、白细胞介素(IL)-1α、IL-6、IL-7、JUN和S100β mRNA的表达。结果 与对照组相比,Lepob/ob 小鼠的体重随年龄的增长而显著增加（P<0.001）,白色脂肪重量、皮下脂肪重量及血糖显著升高（P<0.01,P<0.01,P<0.01）,葡萄糖耐量较低（P<0.001）并产生胰岛素抵抗（P<0.001）;脂肪细胞直径显著增大,且各个脂肪组织均有巨噬细胞浸润灶出现;脂肪细胞内Janus蛋白酪氨酸激酶2(JAK2)、p-JAK2、iNOS、NF-κB、Akt和p-Akt蛋白表达均显著升高（P<0.05）;CCL2、CD44、IL-1α、IL-6、IL-7、JUN和S100β mRNA表达均显著升高。 结论 肥胖诱导小鼠脂肪组织中炎症因子显著表达,促使细胞分泌传导紊乱,导致炎症级联发生。     

RTCB在小鼠不同组织中的表达

目的 检测RTCB在小鼠各种组织中的表达和分布。 方法 提取小鼠胃、前列腺、子宫、卵巢等组织的总蛋白,利用免疫印迹技术,检测RTCB在各组织的相对表达量;通过免疫组织化学技术,检测RTCB在各组织的表达定位情况。 结果 免疫印迹结果显示,小鼠17种组织中RTCB均有表达,输卵管、骨骼肌、肾脏的相对表达量较高,而在膀胱和小肠的相对表达量较低。免疫组织化学结果显示,RTCB在不同组织或同一组织的不同细胞中免疫染色存在差异,尤其在睾丸、附睾、卵巢、子宫、输卵管、小肠等组织某些特定细胞中免疫染色较强。 结论 RTCB可能参与小鼠生殖系统功能的维持。     

Comparison of T1 relaxation times in adipose tissue of severely obese patients and healthy lean subjects measured by 1.5 T MRI

Subcutaneous (SAT) and visceral adipose tissue (VAT) differ in composition, endocrine function and localization in the body. VAT is considered to play a role in the pathogenesis of insulin resistance, type 2 diabetes, fatty liver disease, and other obesity‐related disorders. It has been shown that the amount, distribution, and (cellular) composition of adipose tissue (AT) correlate well with metabolic conditions. In this study, T₁ relaxation times of AT were measured in severely obese subjects and compared with those of healthy lean controls. Here, we tested the hypothesis that T₁ relaxation times of AT differ between lean and obese individuals, but also between VAT and SAT as well as superficial (sSAT) and deep SAT (dSAT) in the same individual. Twenty severely obese subjects (BMI 41.4 ± 4.8 kg/m²) and ten healthy lean controls matched for age (BMI 21.5 ± 1.9 kg/m²) underwent MRI at 1.5 T using a single‐shot fast spin‐echo sequence (short‐tau inversion recovery) at six different inversion times (T_I range 100–1000 ms). T₁ relaxation times were computed for all subjects by fitting the T_I‐dependent MR signal intensities of user‐defined regions of interest in both SAT and VAT to a model function. T₁ times in sSAT and dSAT were only measured in obese patients. For both obese patients and controls, the T₁ times of SAT (275 ± 14 and 301 ± 12 ms) were significantly (p < 0.01) shorter than the respective values in VAT (294 ± 20 and 360 ± 35 ms). Obese subjects also showed significant (p < 0.01) T₁ differences between sSAT (268 ± 11 ms) and dSAT (281 ± 19 ms). More important, T₁ differences in both SAT and VAT were highly significant (p < 0.001) between obese patients and healthy subjects. The results of our pilot study suggest that T₁ relaxation times differ between severely obese patients and lean controls, and may potentially provide an additional means for the non‐invasive assessment of AT conditions and dysfunction. Copyright © 2014 John Wiley & Sons, Ltd.     

Quantitative image analysis in adipose tissue using an automated image analysis system: differential effects of peroxisome proliferator-activated receptor-alpha and -gamma agonist on white and brown adipose tissue morphology in AKR obese and db/db diabetic mice

Morphometric analysis of adipocytes is widely used to demonstrate the effects of antiobesity drugs or anti-diabetic drugs on adipose tissues. However, adipocyte morphometry has been quantitatively performed by manual object extraction using conventional image analysis systems. The authors have developed an automated quantitative image analysis method for adipose tissues using an innovative object-based quantitative image analysis system (eCognition). Using this system, it has been shown quantitatively that morphological features of adipose tissues of mice treated with peroxisome proliferator-activated receptor (PPAR) agonists differ dramatically depending on the type of PPAR agonist. Marked alteration of morphological characteristics of brown adipose tissue (BAT) treated with GI259578A, a PPAR-alpha agonist, was observed in AKR/J (AKR) obese mice. Furthermore, there was a 22.8% decrease in the mean size of adipocytes in white adipose tissue (WAT) compared with vehicle. In diabetic db/db mice, the PPAR-gamma agonist GW347845X decreased the mean size of adipocytes in WAT by 15.4% compared with vehicle. In contrast to changes in WAT, GW347845X increased the mean size of adipocytes in BAT greatly by 96.1% compared with vehicle. These findings suggest that GI259578A may activate fatty acid oxidation in BAT and that GW347845X may cause adipocyte differentiation in WAT and enhancement of lipid storage in BAT.     

Predictive accuracy of single‐ and multi‐slice MRI for the estimation of total visceral adipose tissue in overweight to severely obese patients

The quantification of visceral adipose tissue (VAT) is increasingly being considered for risk assessment and treatment monitoring in obese patients, but is generally time‐consuming. The goals of this work were to semi‐automatically segment and quantify VAT areas of MRI slices at previously proposed anatomical landmarks and to evaluate their predictive power for whole‐abdominal VAT volumes on a relatively large number of patients. One‐hundred and ninety‐seven overweight to severely obese patients (65 males; body mass index, 33.3 ± 3.5 kg/m²; 132 females; body mass index, 34.3 ± 3.2 kg/m²) underwent MRI examination. Total VAT volumes (V_VAT‐T) of the abdominopelvic cavity were quantified by retrospective analysis of two‐point Dixon MRI data (active‐contour segmentation, visual correction and histogram analysis). V_VAT‐T was then compared with VAT areas determined on one or five slices defined at seven anatomical landmarks (lumbar intervertebral spaces, umbilicus and femoral heads) and corresponding conversion factors were determined. Statistical measures were the coefficients of variation and standard deviations σ₁ and σ₅ of the difference between predicted and measured VAT volumes (Bland–Altman analysis). V_VAT‐T was 6.0 ± 2.0 L (2.5–11.2 L) for males and 3.2 ± 1.4 L (0.9–7.7 L) for females. The analysis of five slices yielded a better agreement than the analysis of single slices, required only a little extra time (4 min versus 2 min) and was substantially faster than whole‐abdominal assessment (24 min). Best agreements were found at intervertebral spaces L3–L4 for females (σ_5/1 = 523/608 mL) and L2–L3 for males (σ_5/1 = 613/706 mL). Five‐slice VAT volume estimates at the level of lumbar disc L3–L4 for females and L2–L3 for males can be obtained within 4 min and were a reliable predictor for abdominopelvic VAT volume in overweight to severely adipose patients. One‐slice estimates took only 2 min and were slightly less accurate. These findings may contribute to the implementation of analytical methods for fast and reliable (routine) estimation of VAT volumes in obese patients. Copyright © 2015 John Wiley & Sons, Ltd.     

Fucoidan antagonizes diet-induced obesity and inflammation in mice

Obesity is an escalating global pandemic posing a serious threat to human health. The intervention therapy using weight-reducing drugs, accompanied by lifestyle modification, is a strategy for the treatment of obesity. In the present study, we explored the role of fucoidan, a seaweed compound, on high-fat diet (HFD)-induced obesity in mice. We found that fucoidan treatment significantly reduced the body fat and caused redistribution of visceral and subcutaneous fat in HFD-fed mice. Meanwhile, fucoidan treatment inhibited adipocyte hypertrophy and inflammation in adipose tissue. Collectively, these results suggest that fucoidan may be a promising treatment for obesity and obesity-induced complications.     

白色脂肪"棕色化"调控因子FNDC5/Irisin的研究进展

肥胖是当下全球牵涉范围最广的慢性疾病,也是2型糖尿病、心脑血管疾病以及某些癌症的重要风险因素.其中"白色脂肪棕色化"是目前该领域研究的热点之一,即将体内的储存多余能量的白色脂肪组织(white adipose tissue,WAT)转变为促进消耗能量的棕色脂肪组织(brown adipose tissue,BAT).近年在肌细胞中发现的Ⅲ型纤连蛋白组件包含蛋白5(fibronectin typeⅢdomain containing 5,FNDC5)经胞外切除形成小分子多肽,名为Irisin,具有"白色脂肪棕色化"的功能.     

CD4+ T cells regulate glucose homeostasis independent of adipose tissue dysfunction in mice

Obesity is frequently associated with a chronic low-grade inflammation in the adipose tissue (AT) and impaired glucose homeostasis. Adipose tissue macrophages (ATMs) have been shown to accumulate in the inflamed AT either by means of recruitment from the blood or local proliferation. ATM proliferation and activation can be stimulated by TH2 cytokines, such as IL-4 and IL-13, suggesting involvement of CD4-positive T cells in ATM proliferation and activation. Furthermore, several studies have associated T cells to alterations in glucose metabolism. Therefore, we sought to examine a direct impact of CD4-positive T cells on ATM activation, ATM proliferation and glucose homeostasis using an in vivo depletion model. Surprisingly, CD4 depletion did not affect ATM activation, ATM proliferation, or insulin sensitivity. However, CD4 depletion led to a significant improvement of glucose tolerance. In line with this, we found moderate disturbances in pancreatic endocrine function following CD4 depletion. Hence, our data suggest that the effect on glucose metabolism observed after CD4 depletion might be mediated by organs other than AT and independent of AT inflammation.     

CPZ介导急性脱髓鞘小鼠海马中nestin的表达

目的:探讨双环己酮草酰二腙(cuprizone,CPZ)介导急性脱髓鞘小鼠海马中nestin的表达。方法:用掺入0.2%CPZ的普通饲料饲养C57BL/6小鼠6周,制备脱髓鞘模型,然后使用免疫荧光染色、q RT-PCR、Western Blot方法,检测小鼠脑内髓鞘脱失后海马中nestin的表达变化。结果:(1)体重称量结果显示:CPZ组体重明显低于对照组(P0.01);(2)免疫荧光结果显示:CPZ组海马CA区和DG区颗粒细胞层中nestin阳性细胞明显低于对照组分别为:P0.05,P0.01;(3)Western Blot和q RT-PCR实验结果显示:CPZ组海马中nestin蛋白和m RNA含量均明显低于对照组(P0.05)。结论:CPZ介导小鼠急性脱髓鞘后海马内nestin表达降低,提示髓鞘脱失可能会抑制nestin表达。     

Adipose afferent reflex: sympathetic activation and obesity hypertension

Excessive sympathetic activity contributes to the pathogenesis of hypertension and the progression of the related organ damage. Adipose afferent reflex (AAR) is a sympatho‐excitatory reflex that the afferent activity from white adipose tissue (WAT) increases sympathetic outflow and blood pressure. Hypothalamic paraventricular nucleus (PVN or PVH) is one of the central sites in the control of the AAR, and ionotropic glutamate receptors in the nucleus mediate the AAR. The AAR is enhanced in obesity and obesity hypertension. Enhanced WAT afferent activity and AAR contribute to the excessive sympathetic activation and hypertension in obesity. Blockage of the AAR attenuates the excessive sympathetic activity and hypertension. Leptin may be one of sensors in the WAT for the AAR, and is involved in the enhanced AAR in obesity and hypertension. This review focuses on the neuroanatomical basis and physiological functions of the AAR, and the important role of the enhanced AAR in the pathogenesis of obesity hypertension.     

Apolipoprotein E in diet-induced obesity: a paradigm shift from conventional perception

Apolipoprotein E (APOE) is a major protein component of peripheral and brain lipoprotein transport systems. APOE in peripheral circulation does not cross the blood brain barrier or blood cerebrospinal fluid barrier. As a result, peripheral APOE expression does not affect brain APOE levels and vice versa. Numerous epidemiological studies suggest a key role of peripherally expressed APOE in the development and progression of coronary heart disease while brain APOE has been associated with dementia and Alzheimer’s disease. More recent studies, mainly in experimental mice, suggested a link between Apoe and morbid obesity. According to the latest findings, expression of human apolipoprotein E3 (APOE3) isoform in the brain of mice is associated with a potent inhibition of visceral white adipose tissue (WAT) mitochondrial oxidative phosphorylation leading to significantly reduced substrate oxidation, increased fat accumulation and obesity. In contrast, hepatically expressed APOE3 is associated with a notable shift of substrate oxidation towards non-shivering thermogenesis in visceral WAT mitochondria, leading to resistance to obesity. These novel findings constitute a major paradigm shift from the widely accepted perception that APOE promotes obesity via receptor-mediated postprandial lipid delivery to WAT. Here, we provide a critical review of the latest facts on the role of APOE in morbid obesity.