核受体PPARs与动脉硬化

过氧化物酶体增殖激活受体 (PPARs)是配体激活转录因子 ,存在 3种亚型 ,在多种细胞组织内广泛分布。动脉硬化的特征性变化之一是巨噬细胞源和平滑肌源泡沫细胞在内皮下大量聚集 ,血脂代谢障碍和免疫因素是及其重要的病理生理变化。近年来研究发现 ,PPARα、PPARγ也在血管壁的多种细胞中表达 ,在其配体作用下 ,抑制某些致病基因的表达 ,对动脉粥样硬化斑块的形成和发展具有重要的调节作用     

全反式视黄酸对3T3-L1前脂肪细胞分化及PPARγ和C/EBPα mRNA表达的影响

本研究旨在探讨全反式视黄酸(all trans retinoic acid,ATRA)对3T3-L1前脂肪细胞分化的影响及其机制。培养3T3-L1前脂肪细胞,分别设置对照组以及10-9、10-8、10-7、10-6和10-5 mol/L ATRA的处理组,油红O染色观察3T3-L1前脂肪细胞分化的形态变化;油红O染色提取法分析不同浓度ATRA对3T3-L1前脂肪细胞分化的影响;Real-time PCR技术检测脂肪细胞分化相关基因过氧化物酶体增殖物激活受体γ(peroxisome proliferator activated receptor,PPARγ)、CCAAT/增强子结合蛋白α(CCAAT/enhancer binding proteinα,C/EBPα)mRNA水平的表达。结果表明:10-7、10-6和10-5 mol/L的ATRA抑制3T3-L1前体脂肪细胞的分化(P0.01),而10-9和10-8 mol/L的ATRA对3T3-L1前体脂肪细胞分化没有显著影响(P0.05)。10-5 mol/L的ATRA处理的前脂肪细胞,分化相关基因PPARγ和C/EBPαmRNA的表达减少,与空白对照组比较差异有统计学意义(P0.01)。结果显示,高浓度的ATRA可以抑制3T3-L1前脂肪细胞分化,减少脂肪细胞分化过程中脂质的堆积,机制可能与其抑制脂肪细胞分化相关基因PPARγ和C/EBPαmRNA表达有关。     

过氧化物酶体增殖物激活受体γ信号通路调控脂质代谢的研究进展

过氧化物酶体增殖物激活受体γ(PPARγ)是体内脂肪形成的必需转录因子,处于脂质沉积过程中信号传递通路的核心枢纽位置,促进多能间充质干细胞向脂肪细胞的定向、增殖分化和脂质沉积。本文首先介绍了PPARγ的基本结构和调控靶基因的基本特征,然后以脂肪细胞形成和脂肪沉积为主线,综述了PPARγ信号通路在脂肪细胞形成、脂肪沉积和脂肪因子分泌、营养水平等脂肪代谢过程的调控作用,最后对PPARγ与生物钟相互反馈调节关系以及其在脂质沉积中扮演重要作用进行了概述,对进一步深入综合了解PPARγ对脂肪代谢调控的分子机制具有重要意义,为脂肪代谢及相关疾病的人工干预提供靶基因和新途径。     

过氧化物酶体增殖物激活受体γ调控机体炎症信号通路的研究进展

过氧化物酶体增殖物激活受体γ(Peroxisome Proliferators-activated Receptorγ,PPARγ)是调控炎症反应的关键物质之一,其通过减弱核因子Kappa B(Nuclear Factor-kappa B,NF-κB)、c-Jun氨基末端激酶(c-Jun N-terminalKinase,JNK)活性,降低炎症因子含量从而缓解炎症反应,另一方面PPARγ与腺苷酸激活蛋白激酶(AMP-activated Protein Kinase,AMPK)互相抑制,共同维持动物正常机能。本文综述了PPARγ对动物炎症通路的调控作用,为其进一步研究和应用提供参考。     

过氧化物酶体增殖剂激活受体研究进展

随着人们生活水平的提高,对畜禽的肉质提出了更高要求。因此,改善肉质就成为育种工作者的主要任务之一。适量的皮下脂肪可改善胴体外观,但皮下脂肪和腹脂太多则不好,而较高含量的肌内脂肪(I MF)则能改善肉品质。近几年来,畜禽脂肪性状相关基因的研究已成为动物遗传育种研究的热     

冷应激对猪脂肪、肝脏、心脏与肾脏组织中PPARγ2 mRNA及蛋白表达的影响

为了研究冷应激对机体的影响及过氧化物酶体增殖物激活受体γ2（PPARγ2）在冷应激中的作用,本试验选用30头军牧一号猪,并随机分成5组,包括常温对照组和4个冷应激组。常温组在（21±2）℃饲养,冷应激组的温度设置分别为：（-10±2）、（-5±2）、（0±2）、（5±2）℃。冷应激2h屠宰后分别采集猪腹腔脂肪、颈部皮下脂肪、胸部皮下脂肪、肝脏、心脏与肾脏组织样品提取总RNA与总蛋白。通过荧光定量PCR技术检测了PPARγ2mR-NA的表达量;通过Western blot检测PPARγ2蛋白表达量。结果显示,各温度组猪腹腔脂肪、颈部皮下脂肪、胸部皮下脂肪、肝脏、心脏PPARγ2mRNA及蛋白表达量总体上差异显著（P〈0.01）,肾脏PPARγ2mRNA表达量总体显著升高,但其蛋白表达量总体呈下降趋势。结果表明,PPARγ2对冷刺激非常敏感,它除了可以调节冷应激时的脂肪代谢平衡,还对心脏有较好的保护作用,但是对肾脏的作用有限。本试验显示了冷应激中PPARγ2在脂肪代谢与能量代谢中作用,为研究冷应激对机体的影响及畜禽品质的提高奠定了基础。     

PPARγ和PCNA在口腔鳞癌组织的表达及临床意义

目的 探讨过氧化物酶体增殖物激活受体(PPARγ)与增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)在口腔鳞癌中(oral squamous-cell carcinoma,OSCC)的表达及其生物学意义.方法 采用免疫组织化学和流式细胞术检测50例口腔鳞状细胞癌、癌旁黏膜(距瘤缘2 cm)和切缘正常黏膜(距瘤缘≥5 cm,镜下未见癌浸润)标本中PPARγ和PCNA的表达.结果 PPARγ在癌组织中的阳性表达率为68.0% (34/50),高于癌旁组织(26.0%,13/50)和正常黏膜组织(2.0%,1/50) (P ＜0.05);PCNA在癌组织中的阳性表达率为72.0% (36/50),高于癌旁组织(26.0%,13/50)和正常黏膜组织(4.0%,2/50)(P＜0.05).流式细胞术检测PPARγ在鳞癌组织中的表达为(396.56±33.39),明显高于癌旁组织(333.36±15.93)及正常口腔黏膜组织(289.28±13.80)(P＜0.05).PCNA在鳞癌组织中的表达为(543.11±41.55),明显高于癌旁组织(456.97±23.86)和正常口腔黏膜组织(409.40±40.07) (P ＜0.05).PPARγ和PCNA的表达与细胞分化程度、淋巴结转移均有相关性(PPARγ,r分别为0.497、0.392,P＜0.05;PCNA,r分别为0.324、0.561,P＜0.05),且二者在口腔鳞癌中的表达呈正相关.结论 口腔鳞癌组织中PPARγ和PCNA的表达均升高,可能与口腔鳞癌的发生、发展相关.     

乙酸浓度对奶牛乳腺上皮细胞甘油三酯含量及瘦素和过氧化物酶增殖物激活受体γ基因表达量的影响

本试验旨在研究乙酸浓度对奶牛乳腺上皮细胞甘油三酯(TAG)含量及瘦素(leptin)和过氧化物酶增殖物激活受体γ(PPARγ)基因表达量的影响。将传至第3代的奶牛乳腺上皮细胞以适宜的密度培养48 h后,随机分为6个处理,各处理分别采用乙酸浓度为0(对照组)、4、6、8、10和12 mmol/L的培养液。置于37℃5%CO2培养箱继续培养48 h。收集细胞,观测脂滴形成状况,测定TAG含量及leptin和PPARγ基因表达量。结果表明:随乙酸浓度的增加,培养的奶牛脂肪前体细胞脂滴形成增多;随乙酸浓度的增加,TAG含量和PPARγ基因表达量均呈显著的线性或二次曲线增加(P<0.05),且以乙酸浓度为10和12 mmol/L时效果较好;一定浓度的乙酸可上调leptin基因表达量,尤以浓度为8、10 mmol/L时上调作用较好。结果提示,乙酸对奶牛乳腺上皮细胞内脂滴的形成、TAG的积累、leptin和PPARγ基因的表达有显著的促进作用。本试验条件下,乙酸浓度为10～12 mmol/L时能较好地促进PPARγ基因的表达,浓度为8～10 mmol/L时能较好地促进leptin基因的表达。     

白色脂肪棕色化及其与疾病的相关性研究进展

脂肪组织主要包括白色脂肪组织和棕色脂肪组织。白色脂肪组织的主要功能是储存能量,棕色脂肪组织的主要功能是产热耗能。白色脂肪棕色化的信号通路复杂多样,其相关的转录因子有过氧化物酶体增殖物激活受体(peroxisome proliferator-activated receptors, PPARs)、PR结构域蛋白16(PR domain containing 16, PRDM16)和过氧化物酶体增殖物激活受体γ辅助激活因子-1α(peroxisome proliferator-activated receptor gamma coactivator 1α, PGC-1α),同时也受骨形态发生蛋白(bone morphogenetic proteins, BMPs)和鸢尾素(irisin)的调节。白色脂肪棕色化能够激活米色细胞,增加机体的产热耗能,是治疗肥胖、胰岛素抵抗、脂肪肝、心脑血管疾病等的新方向。然而,白色脂肪棕色化是一把双刃剑,可能引起动脉粥样硬化、恶病质和肝脂肪变性等多种疾病。因此,文章对白色脂肪棕色化的调控因素、信号通路及其对疾病的影响进行综述,以期为发挥白色脂肪棕色化的优势、减...     

过氧化物酶体增殖物激活受体对鱼类代谢的调节作用北大核心

过氧化物酶体增殖物激活受体(PPARs)是核激素受体家族中的配体激活受体,在糖脂代谢、细胞分化、胚胎发育、脂肪生成等过程中发挥重要作用。文章概述鱼类PPARs基因的克隆与表达,阐述了PPARs在鱼类糖脂代谢和能量代谢中的作用,旨为PPARs调节鱼类的糖脂代谢作用机制提供参考。     

Birth weight and gender determine expression of adipogenic, lipogenic and adipokine genes in perirenal adipose tissue in the young adult sheep

Epidemiological studies have demonstrated that low birth weight is associated with an increased incidence of visceral obesity and metabolic disorders in later life. In the present study, we have determined the impact of birth weight and gender on gene expression in visceral adipose tissue (VAT) in the young adult sheep. Lambs (n=19, birth weight range 2.6-7.55 kg) were born at term and growth monitored for 22.4+/-0.2 weeks, when body composition was determined by Dual X-ray Absorptiometry (DXA) and samples of VAT and subcutaneous (SCAT) adipose tissue collected. Plasma samples were collected at post-mortem for the determination of free fatty acids (FFA), glucose and insulin concentrations. Peroxisome-Proliferator Activated Receptor-gamma (PPARgamma), glycerol-3-phosphate dehydrogenase (G3PDH), lipoprotein lipase (LPL), adiponectin and leptin mRNA expression was determined by qRT-PCR. Fractional growth rate in postnatal weeks 1-3 was inversely related to birth weight in both males and females (R2=0.22, P<0.05, n=19). PPARgamma mRNA expression in VAT, but not SCAT, was inversely related to birth weight (R2=0.60, P<0.01, n=18). In males, but not females, PPARgamma mRNA in VAT was directly related to G3PDH mRNA expression (R2=0.69, P<0.01, n=9). Plasma FFA concentrations were inversely related to birth weight in both males and females (R2=0.22, P<0.05, n=19). These findings demonstrate that low birth weight is associated with an increased expression of a key adipogenic factor in visceral adipose tissue in young adulthood. In males, this is associated with an increased expression of lipogenic genes, and this may contribute to the increased propensity for visceral obesity in low birth weight males compared to females.     

地塞米松对猪原代脂肪细胞分化及perilipin和PPARγ mRNA表达的影响

由断奶仔猪皮下脂肪分离血管基质细胞,增殖培养至80%融合时以10-6mol/L地塞米松处理48 h,同时设地塞米松拮抗剂RU486对照组。采用油红O染色提取法测定细胞内甘油三酯含量,相对定量实时荧光PCR方法检测细胞perilipin,GR,C/EBPβ,PPARγmRNA表达。结果显示,地塞米松显著增加细胞甘油三酯含量(P0.05),添加RU486后这种作用显著降低(P0.05);地塞米松处理组细胞中perilipin,PPARγ的mRNA表达显著高于对照组(P0.05),而C/EBPβmRNA表达较对照组显著降低(P0.05);GR mRNA表达与对照组相比无显著差异。以上结果提示:地塞米松能显著促进猪原代脂肪细胞的分化,这种作用可能通过上调perilipin mRNA表达而实现,其中PPARγ基因参与了调节。     

过氧化物酶体增殖剂激活受体γ的结构特征和生物学功能

过氧化物酶体增殖剂激活受体γ(PPARγ)是核激素受体超家族转录因子成员之一,在机体能量代谢、细胞分化、神经损伤、炎性反应及心脑血管疾病中发挥重要的调控作用。本文就PPARγ及其配体的结构特征和生物学功能作了简要介绍。     

Regulation of hepatic peroxisome proliferator‐activated receptor α expression but not adiponectin by dietary protein in finishing pigs

Soy protein regulates adiponectin and peroxisome proliferator‐activated receptor α (PPARα) in some species, but the effect of dietary soy protein on adiponectin and PPARα in the pig has not been studied. Therefore, the objective of this study was to determine whether soya bean meal reduction or replacement influences serum adiponectin, adiponectin mRNA, serum metabolites and the expression of PPARα and other genes involved in lipid deposition. Thirty‐three pigs (11 pigs per treatment) were subjected to one of three dietary treatments: (i) reduced crude protein (CP) diet containing soya bean meal (RCP‐Soy), (ii) high CP diet containing soya bean meal (HCP‐Soy) or (iii) high CP diet with corn gluten meal replacing soya bean meal (HCP‐CGM) for 35 days. Dietary treatment had no effect on overall growth performance, feed intake or measures of body composition. There was no effect of dietary treatment on serum adiponectin or leptin. Dietary treatment did not affect the abundance of the mRNAs for adiponectin, PPARα, PPARγ2, lipoprotein lipase or fatty acid synthase in adipose tissue. The mRNA expression of PPARα, PPARγ2, lipoprotein lipase or fatty acid synthetase in loin muscle was not affected by dietary treatment. In liver tissue, the relative abundance of PPARα mRNA was greater (p < 0.05) in pigs fed the HCP‐Soy diets when compared to pigs fed RCP‐Soy or HCP‐CGM diets. Hepatic mRNA expression of acyl‐CoA oxidase or fatty acid synthase was not affected by dietary treatment. Western blot analysis indicated that hepatic PPARα protein levels were decreased (p < 0.05) in pigs fed the RCP‐Soy diets when compared to pigs fed the HCP‐Soy diets. These data suggest that increasing the soy protein content of swine diets increases hepatic expression of PPARα without associated changes in body composition.     

抑制剂T0070907对鸡PPARγ基因表达影响的研究

为了验证过氧化物酶体增殖物激活受体(PPAR)γ选择性抑制剂T0070907对鸡PPARγ基因表达的促进作用,本研究利用荧光定量PCR检测了不同浓度T0070907对鸡成纤维细胞(DF-1细胞)中PPARγ基因mRNA转录水平的影响,结果显示,随着T0070907浓度的增加,鸡PPARγ基因的表达量逐渐升高,并且在T0070907浓度为5μmol/L时极显著高于对照组(p<0.01);利用western blot检测了T0070907对PPARγ蛋白表达的影响,结果显示,5μmol/L的T0070907对DF-1细胞中PPARγ2蛋白的表达有一定的促进作用;利用双荧光素酶报告基因技术检测了不同浓度T0070907对PPRE报告基因活性的影响,结果显示,随着T0070907浓度的增加,DF-1细胞中PPRE报告基因活性逐渐增强,并且在T0070907浓度为0.5μmol/L时该报告基因活性显著高于对照组(p<0.05),当T0070907浓度为2μmol/L、5μmol/L时,与对照组之间的差异达到极显著水平(p<0.01);利用双荧光素酶报告基因技术检测了T0070907和罗格列酮(Rosi)对PPRE报告基因活性的影响,结果显示,单独添加T0070907或Rosi均可显著增强PPRE报告基因活性(p<0.05),同时,添加T0070907并不能降低Rosi对PPRE报告基因活性的促进作用。本研究结果表明,作为PPARγ抑制剂的T0070907对鸡PPARγ基因的mRNA的转录水平、蛋白表达及其蛋白活性均具有促进作用,推测与哺乳动物不同,鸡PPARγ可能具有其独特的表达方式和调控机制。本研究结果对完善PPARγ抑制剂在生理学及药理学上的研究、为PPARγ功能研究选择准确的拮抗剂、预防和治疗炎症相关疾病等方面具有重要意义。     

Myostatin inhibits differentiation of bovine preadipocyte

We investigated the effect of myostatin on the differentiation of bovine preadipocyte. Stromal-vascular cells containing preadipocytes were prepared from perirenal adipose tissue of approximately 30-month-old Japanese Black steers. After confluence, the differentiation was induced by 1-methyl-3-isobutyl-xanthine, dexamethasone, insulin, and troglitasone for 2 days, and then subsequently cultured for 6 days. The cells were treated with myostatin during the induction of differentiation (the early phase of differentiation) or throughout the differentiation period. We measured the terminal differentiation markers such as glycerol-3-phosphate dehydrogenase activity, lipid accumulation, and the expression of adipocyte fatty acid-binding protein mRNA at the end of cultures. The treatment with myostatin throughout the differentiation period severely suppressed the induction of all differentiation markers. The treatment with myostatin in the early phase of differentiation also suppressed the induction of terminal differentiation markers but three-fold higher dose of myostatin was required for the suppression compared with its treatment throughout the differentiation period. Myostatin treatment reduced the expression of peroxisome proliferator-activated receptor (PPAR) gamma mRNA and interfered with the induction of CCAAT/enhancer binding protein (C/EBP) alpha mRNA. We also observed that follistatin stimulates preadipocyte differentiation in the presence of myostatin. These results suggest that myostatin inhibits bovine preadiopocyte differentiation through suppressing PPARgamma and C/EBPalpha mRNA expressions and that follistatin counteracts the suppressive effect of myostatin.     

LPS诱导不同品系雏鸡炎症反应相关基因的差异表达分析

分别以AA+肉仔鸡和海兰褐蛋雏鸡为研究对象,采用大肠杆菌脂多糖(LPS)连续3d腹腔注射11日龄雏鸡,收集血液、肝脏、胸腺、法氏囊、脾脏等组织,利用RT-PCR定量分析炎症反应相关基因akirin2、PPARγ和几种miRNA的转录活性变化。结果表明:在LPS接种肉鸡(AA+肉鸡)的肝脏、法氏囊和脾脏中akirin2基因转录活性均显著下调(P0.01),PPARγ基因在肝脏、法氏囊中转录水平也均显著下调(P0.01);在LPS接种蛋鸡(海兰褐鸡)的胸腺中akirin2基因转录活性显著上调(P0.01),但PPARγ基因在各组织中的转录水平差异均不显著;miR-146a(P0.05)、miR-21(P0.01)和miR-155(P0.01)在2个品系鸡的肝脏中表达均显著下调。研究不同品系鸡LPS诱导下相关基因转录活性的变化关系,对于深入了解不同品系鸡炎症反应分子机制的差异和开发炎症反应早期诊断的分子标记物具有重要的理论和实践意义。     

九龙牦牛PPARγ基因的克隆及其表达谱分析

根据普通牛(Bos tarus)过氧化物酶体增殖物激活受体γ(PPARγ)基因序列设计引物,用成年九龙牦牛(Bos grunniens)脂肪组织总RNA,经RT-PCR扩增获得了PPARγ基因序列(GenBank登陆号:GU061328),其中cDNA的ORF为1 428 bp,编码475个氨基酸,与普通牛PPARγ氨基酸的同源性达99%,有2个氨基酸发生突变。利用半定量RT-PCR分析九龙牦牛PPARγ基因的mRNA表达特性。结果表明:在脂肪、背最长肌、心、肝、肾、脾和肺脏中均检测到PPARγ基因的表达,并且在脂肪组织中表达量极显著高于其他组织(P0.01),在肝脏和脾脏中亦有较高表达。PPARγ基因在背最长肌中的表达5.5岁九龙牦牛显著高于0.5、3.5岁和9岁以上,其表达与背最长肌的肌内脂肪含量未见显著相关性。