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。     

过氧化物酶体增殖剂受体与脂质代谢调控

综述了过氧化物酶体增殖剂受体在动物体内的分布、结构与转录调节机制及其对脂肪细胞分化、脂质代谢的调控。     

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     

过氧化物酶体增殖物激活受体γ参与鸡脂质代谢调控的机理

营养与遗传互作对代谢通路的影响已成为家禽科学的研究热点。脂肪主要用于动物体能量贮存,并参与细胞膜构建、基因表达调控、以及作为众多调节因子的前体物。从功能分析,食物中脂肪可通过直接改变基因表达进而影响肝脏脂肪酸和脂质生发酶的合成。核激素受体为一类配体激活的转录因子,可直接或间接调节一系列参与脂质代谢或炎症反应过程。过氧化物酶体增殖物激活受体(PPARs)作为核激素受体超家族转录因子之一,PPARγ是脂肪组织的主要调节基因,参与一系列与脂肪生成相关基因的表达调控。因此,根据鸡脂肪代谢研究构建PPARγ基因表达调控的网络图谱,对于了解鸡脂肪代谢调控具有重要意义。     

过氧化物酶体增殖剂激活受体的研究进展

过氧化物酶体增殖物激活受体（PPARs）是一种核内受体转录因子,具有多种生物学效应。可促进脂肪细胞分化和脂肪生成,增强机体对胰岛素的敏感性,调解体内糖平衡,抑制炎症因子生成及炎症反应,影响肿瘤生长,对心血管产生保护效应和神经保护作用。PPAR有三种亚型,分别是PPARα,PPARβ和PPARγ,其中PPARα在最新的研究中表明,其具有影响动物耐热机制的作用。     

过氧化物酶体增殖剂激活受体的研究进展

过氧化物酶体增殖物激活受体(PPARs)是一种核内受体转录因子,具有多种生物学效应.可促进脂肪细胞分化和脂肪生成,增强机体对胰岛素的敏感性,调解体内糖平衡,抑制炎症因子生成及炎症反应,影响肿瘤生长,对心血管产生保护效应和神经保护作用.PPAR有三种亚型,分别是PPARα,PPARβ和PPARγ,其中PPARα在最新的研...     

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。     

过氧化物酶体增殖物激活受体调控幼龄反刍动物瘤胃的生酮作用及其机制

发育良好的瘤胃对于幼龄反刍动物至关重要,不仅关乎其自身的健康,也与其成年后生产性能的发挥息息相关。对于刚出生的幼龄反刍动物,其瘤胃不具有生酮功能,随日龄的增加,瘤胃形态与功能逐渐发育成熟,逐渐具备了该功能。生酮作用是瘤胃发育成熟的关键因素,β-羟丁酸(BHBA)被认为是瘤胃发育成熟的标志。近十几年来,许多学者针对影响瘤胃生酮作用的因素进行了大量研究,发现过氧化物酶体增殖物激活受体(PPARs)对于瘤胃生酮和上皮细胞增殖十分重要,转录因子PPARs可以影响到生酮作用关键酶3-羟基-3-甲基戊二酰辅酶A合成酶2(HMGCS2)的表达。但目前对于PPARs调控瘤胃生酮作用分子机制的了解仍然十分有限,因此本文针对PPARs调控幼龄反刍动物瘤胃发育的研究进展进行了综述。     

猪脂肪的细胞形态学与脂肪代谢酶的研究

对脂肪沉积能力不同的甘肃黑猪I系和杜黑背部皮下脂肪组织的生长发育进行了研究。利用组织切片法 ,观察了两种猪的脂肪细胞形态 ,发现脂肪沉积能力强的甘肃黑猪I系的脂肪细胞在 3月龄显著大于杜黑 (P <0 .0 1) ,甘肃黑猪Ⅰ系在试验后期 ,几乎观察不到多小室脂肪细胞 ,表明它的脂肪组织发育快 ,成熟也快。甘肃黑猪I系的脂蛋白脂酶 (LPL)活性在 3月龄极显著高于杜黑猪的酶活性 (P <0 .0 1) ,两种猪的LPL活性后期均表现为下降趋势 ,甘肃黑猪Ⅰ系的NADP -MDH活性显著高于杜黑的酶活性     

Differential expression of peroxisome proliferator-activated receptors alpha and gamma gene in various chicken tissues

The peroxisome proliferator-activated receptors (PPARs) are the members of superfamily of nuclear hormone receptors. A great number of studies in rodent and human have shown that PPARs were involved in the lipids metabolism. The goal of the current study was to investigate the expression pattern of PPAR genes in various tissues of chicken. The tissue samples (heart, liver, spleen, lung, kidney, stomach, intestine, brain, breast muscle and adipose) were collected from six Arber Acres broilers (8 weeks old, male and female birds are half and half). Semi-quantitative RT-PCR and Northern blot were used to characterize the expression of PPAR-alpha and PPAR-gamma genes in the above tissues. By semi-quantitative RT-PCR, the results showed the expression level of PPAR-alpha gene was higher in brain, lung, kidney, heart and intestine, medium in stomach, liver and adipose than in spleen, and it did not express in breast muscle. The expression level of PPAR-gamma gene was higher in adipose, medium in brain and kidney than in spleen, heart, lung, stomach and intestine, but it did not express in liver and breast muscle. Northern blot results showed that PPAR-alpha gene expressed in heart, liver, kidney and stomach, and the intensity of hybridization signal was the stronger in liver and kidney than in other tissues, however, PPAR-gamma gene only expressed in adipose and kidney tissues. The results of this study showed the profile of PPAR gene expression in the chicken was similar to that in rodent, human and pig. However the expression profile of chicken also have its own specific trait, i.e. compared with mammals, PPAR-alpha gene can not be detected in skeletal muscle and PPAR-gamma gene can be stronger expressed in kidney tissues. This work will provide some basic data for the PPAR genes expression and lipids metabolism of birds.     

过氧化物酶体增殖物激活受体(PPARs)在细胞及整个生物水平的多方面作用

代谢综合征是多种代谢性疾病的总称,包括肥胖、血脂异常、葡糖耐受不良、炎症和高血压.近年许多研究表明,PPAR可以改善这类代谢异常情况.PPARs是细胞核激素受体超家族配体激活转录因子,分为PPARα、PPARβ/δ、PPARγ三个亚型,分布在各不同组织,功能涵盖广泛.     

The interplay between non-esterified fatty acids and bovine peroxisome proliferator-activated receptors: results of an in vitro hybrid approach

Background: In dairy cows circulating non-esterified fatty acids(NEFA) increase early post-partum while liver and other tissues undergo adaptation to greater lipid metabolism, mainly regulated by peroxisome proliferator-activated receptors(PPAR). PPAR are activated by fatty acids(FA), but it remains to be demonstrated that circulating NEFA or dietary FA activate bovine PPAR. We hypothesized that circulating NEFA and dietary FA activate PPAR in dairy cows.Methods: The dose-response activation of PPAR by NEFA or dietary FA was assessed using HP300 e digital dispenser and luciferase reporter in several bovine cell types. Cells were treated with blood plasma isolated from Jersey cows before and after parturition, NEFA isolated from the blood plasma, FA released from lipoproteins using milk lipoprotein lipase(LPL), and palmitic acid(C16:0). Effect on each PPAR isotype was assessed using specific synthetic inhibitors.Results: NEFA isolated from blood serum activate PPAR linearly up to ~ 4-fold at 400 μmol/L in MAC-T cells but had cytotoxic effect. Addition of albumin to the culture media decreases cytotoxic effects of NEFA but also PPAR activation by ~ 2-fold. Treating cells with serum from peripartum cows reveals that much of the PPAR activation can be explained by the amount of NEFA in the serum(R~2 = 0.91) and that the response to serum NEFA follows a quadratic tendency, with peak activation around 1.4 mmol/L. Analysis of PPAR activation by serum in MAC-T, BFH-12 and BPAEC cells revealed that most of the activation is explained by the activity of PPARδ and PPARγ, but not PPARα. Palmitic acid activated PPAR when added in culture media or blood serum but the activation was limited to PPARδ and PPARα and the response was nil in serum from post-partum cows. The addition of LPL to the serum increased > 1.5-fold PPAR activation.Conclusion: Our results support dose-dependent activation of PPAR by circulating NEFA in bovine, specifically δand γ isotypes. Data also support the possibility of increasing PPAR activation by dietary FA;however, this nutrigenomics approach maybe only effective in pre-partum but not post-partum cows.     

Ectopic expression of porcine peroxisome proliferator-activated receptor delta regulates adipogenesis in mouse myoblasts

Peroxisome proliferator-activated receptor gamma (PPARgamma) plays a critical role in regulating adipogenesis. The expression of peroxisome proliferator-activated receptor delta (PPARdelta) precedes that of PPARgamma during adipocyte differentiation in rodents. The current experiment was designed to study the function of porcine PPARdelta and the interaction of PPARdelta and PPARgamma in adipocyte differentiation. Inhibition of myogenesis was observed in mouse myoblasts expressing porcine PPARdelta, similar to myoblasts expressing PPARgamma. Treatment of myoblasts expressing PPARdelta with ligands for both PPARdelta and PPARgamma enhanced lipogenesis and adipogenesis to a greater extent than treatment with a PPARgamma ligand alone, suggesting that both genes were involved in regulating lipogenesis and adipogenesis. The ability to transdifferentiate myoblasts into adipocytes was decreased in myoblasts coexpressing PPARdelta with either wild type or mutated PPARgamma (Ser 112 was mutated to Ala; the mutated PPARgamma is more active than the wild type) compared with myoblasts expressing PPARgamma alone. Adipocyte differentiation in myoblasts coexpressing PPARdelta and mutated PPARgamma was greater than in myoblasts coexpressing PPARdelta and wild type PPARgamma, confirming that Ser 112 is important for the function of PPARgamma. Taken together, our results demonstrate that overexpression of PPARdelta inhibits myotube formation and also enhances adipocyte differentiation. However, the complexity and interaction of PPARdelta and PPARgamma in adipogenesis are not clearly understood.     

Transplacental induction of fatty acid oxidation in term fetal pigs by the peroxisome proliferator-activated receptor alpha agonist clofibrate

Background: To induce peroxisomal proliferator-activated receptor α(PPARα) expression and increase milk fat utilization in pigs at birth, the effect of maternal feeding of the PPARα agonist, clofibrate(2-(4-chlorophenoxy)-2-methyl-propanoic acid, ethyl ester), on fatty acid oxidation was examined at ful-term delivery(0 h) and 24 h after delivery in this study.Each group of pigs(n = 10) was delivered from pregnant sows fed a commercial diet with or without 0.8% clofibrate for the last 7 d of gestation. Blood samples were col ected from the utero-ovarian artery of the sows and the umbilical cords of the pigs as they were removed from the sows by C-section on day 113 of gestation.Results: HPLC analysis identified that clofibric acid was present in the plasma of the clofibrate-fed sow(~4.2 μg/m L)and its offspring(~1.5 μg/m L). Furthermore, the maternal-fed clofibrate had no impact on the liver weight of the pigs at 0 h and 24 h, but hepatic fatty acid oxidation examined in fresh homogenates showed that clofibrate increased(P 0.01)~(14)C-accumulation in CO2 and acid soluble products 2.9-fold from [1-~(14)C]-oleic acid and 1.6-fold from[1-~(14)C]-lignoceric acid respectively. Correspondingly, clofibrate increased fetal hepatic carnitine palmitoyltransferase(CPT)and acyl-Co A oxidase(ACO) activities by 36% and 42% over controls(P 0.036). The m RNA abundance of CPT I was 20-fold higher in pigs exposed to clofibrate(P 0.0001) but no differences were detected for ACO and PPARα m RNA between the two groups.Conclusion: These data demonstrate that dietary clofibrate is absorbed by the sow, crosses the placental membrane, and enters fetal circulation to induce hepatic fatty acid oxidation by increasing the CPT and ACO activities of the newborn.     

Transplacental induction of fatty acid oxidation in term fetal pigs by the peroxisome proliferator-activated receptor alpha agonist clofibrate

Background

To induce peroxisomal proliferator-activated receptor α (PPARα) expression and increase milk fat utilization in pigs at birth, the effect of maternal feeding of the PPARα agonist, clofibrate (2-(4-chlorophenoxy)-2-methyl-propanoic acid, ethyl ester), on fatty acid oxidation was examined at full-term delivery (0 h) and 24 h after delivery in this study. Each group of pigs (n = 10) was delivered from pregnant sows fed a commercial diet with or without 0.8% clofibrate for the last 7 d of gestation. Blood samples were collected from the utero-ovarian artery of the sows and the umbilical cords of the pigs as they were removed from the sows by C-section on day 113 of gestation.

Results

HPLC analysis identified that clofibric acid was present in the plasma of the clofibrate-fed sow (~4.2 μg/mL) and its offspring (~1.5 μg/mL). Furthermore, the maternal-fed clofibrate had no impact on the liver weight of the pigs at 0 h and 24 h, but hepatic fatty acid oxidation examined in fresh homogenates showed that clofibrate increased (P < 0.01) ¹⁴C-accumulation in CO₂ and acid soluble products 2.9-fold from [1-¹⁴C]-oleic acid and 1.6-fold from [1-¹⁴C]-lignoceric acid respectively. Correspondingly, clofibrate increased fetal hepatic carnitine palmitoyltransferase (CPT) and acyl-CoA oxidase (ACO) activities by 36% and 42% over controls (P < 0.036). The mRNA abundance of CPT I was 20-fold higher in pigs exposed to clofibrate (P < 0.0001) but no differences were detected for ACO and PPARα mRNA between the two groups.

Conclusion

These data demonstrate that dietary clofibrate is absorbed by the sow, crosses the placental membrane, and enters fetal circulation to induce hepatic fatty acid oxidation by increasing the CPT and ACO activities of the newborn.