氨基酸介导的TOR信号传导通路研究进展

TOR(target of rapamycin)是一种进化上十分保守的丝氨酸(Ser)/苏氨酸(Thr)蛋白激酶,可以感知营养状况、能量、生长因子等信号,进而调节细胞的生长、增殖和凋亡等生理进程.本文综述了TOR的上、下游信号传导通路及各种氨基酸对TOR信号传导通路的影响,为探讨氨基酸调控蛋白质合成的作用机制及建立精确...     

TOR信号通路的研究进展

TOR信号通路是一种重要的细胞代谢调节通路,可以通过感知营养状态来调节细胞生长、增殖和代谢等过程。使用营养的手段调节TOR信号通路是当前研究的热点。文章综述了TOR信号通路的激活方式及其在畜禽中对生长发育、免疫调节、繁殖和饲料营养等方面的研究进展,研究TOR信号通路的特点和调节机制,为畜禽产业的发展提供参考。     

腺苷酸活化蛋白激酶/哺乳动物雷帕霉素靶蛋白信号通路介导能量和必需氨基酸调控乳蛋白合成

乳蛋白合成是以必需氨基酸为底物的耗能过程。腺苷酸活化蛋白激酶(AMPK)是AMPK信号通路的重要分子;可通过感受细胞能量状态的方式来维持能量平衡,从而为乳蛋白合成提供充足的能量。哺乳动物雷帕霉素靶蛋白(m TOR)是AMPK信号通路重要的下游靶点;必需氨基酸主要以m TOR介导的信号通路调控乳蛋白合成。本文主要综述了能量和必需氨基酸通过AMPK/m TOR信号通路对乳蛋白合成调控的研究进展,旨在进一步阐明能量和必需氨基酸对乳蛋白合成调控的作用机理。     

氨基酸感知与代谢调控的研究进展

氨基酸不仅是蛋白质和其他含氮化合物合成的重要前体,还参与体内主要代谢途径的调控。当氨基酸不足时,机体内多种机制参与调节体内平衡,包括快速停止蛋白质合成、增加氨基酸合成和转运,以及加强自噬作用。越来越多的学者证明氨基酸可作为信号分子参与细胞内信号传导过程,可以调节其他营养素如脂肪和能量的代谢,最终导致机体整体代谢的改变。本文主要综述细胞内氨基酸的营养感知与应答机制,涉及氨基酸应答(AAR)和雷帕霉素靶蛋白(TOR)2条信号转导通路,并探讨这2条信号通路对下游营养素代谢途径的调节。     

乳腺内氨基酸调控乳蛋白合成的分子作用机制

作为维持哺乳动物生命活动重要的"生物工厂",乳腺利用从流经血液中摄取的氨基酸等营养物质为底物合成乳蛋白。研究证实,氨基酸还可作为一种信号因子,通过乳腺内多种信号级联传导通路,调控乳蛋白基因的转录及翻译过程,从而影响乳腺中乳蛋白的合成。酪氨酸蛋白激酶-信号转导子和转录激活子(JAK-STAT)信号通路和哺乳动物雷帕霉素靶蛋白(m TOR)信号通路是乳蛋白基因转录和翻译过程中的主要调控路径。本文综述了乳腺JAKSTAT和m TOR信号通路的分子机制及氨基酸通过这些通路调控乳蛋白合成的研究进展,旨在进一步阐明氨基酸调控乳蛋白合成的作用机理。     

G蛋白偶联受体及G蛋白在细胞信息传导中的作用

G蛋白介导的信号传导系统是细胞中最常见的信号传递方式。G蛋白偶联的信号传导系统由G蛋白偶联受体、G蛋白和效应器组成。1977年Ross和Gilman证实G蛋白可作为细胞受体与效应器之间的转换器。大量研究发现,G蛋白偶联信号传导系统普遍存在于动植物中。主要阐述了G蛋白和GPCRs在细胞传导中的作用。     

动物脂滴结构及功能研究进展

脂滴是脂肪组织的基本单位,是维持脂质和能量稳态的一种动态细胞器,脂滴相关蛋白参与调控胞内脂类代谢、膜运输以及信号传导等多个生理过程.脂滴在动物各个组织器官中的功能不尽相同,可通过营养及生理手段调节畜禽外周组织中的脂滴变化,进一步影响畜禽胴体性状及肉品质.本文简述了脂滴的生物学结构、脂滴蛋白分类、脂滴重塑、脂滴生物学功能...     

氨基酸调节哺乳动物雷帕霉素靶蛋白复合体1信号通路的分子机制

哺乳动物雷帕霉素靶蛋白复合体1(mTORC1)信号通路能够感受一系列细胞内外环境因素的变化,如氨基酸浓度、能量水平、生长因子等进而调节细胞生长。氨基酸不仅是合成蛋白质的底物,也可作为信号分子激活mTORC1信号通路,促进蛋白质合成。溶酶体是氨基酸激活mTORC1信号通路过程中一个重要细胞器,mTORC1感应氨基酸的上游信号通路需要溶酶体相关蛋白及胞浆蛋白的参与完成。本文综述了氨基酸调节mTORC1信号通路的分子机制,为营养因子调控蛋白质合成的关键通路提供参考。     

酪氨酸激酶-信号转导及转录激活因子(JAK-STAT)信号通路及其在动物营养中的研究进展

细胞受到刺激时可产生细胞因子,但所产生的细胞因子并没有激酶活性,所以细胞因子如何将信号传递至细胞内是一直困扰人们的问题.JAK-STAT(酪氨酸激酶-信号转导及转录激活因子)信号通路的发现解决了胞浆区不含蛋白激酶活性的细胞因子如何转导信号这一难题,JAK-STAT是一条极其快速的从细胞外到细胞核的信号转导通路,是一条复杂的信号传导途径.研究发现,JAK-STAT信号通路与细胞生长、增殖和分化都有着十分密切的关系,近年来对JAK-STAT的研究成为热点并取得了一系列的进展.本文就JAK-STAT信号通路的基本结构、激活及转导过程及其在动物营养方面取得的进展作相关阐述.     

营养水平对梅山猪和大白猪卵巢发育的影响及机制

卵巢发育状况是影响胚胎数量和质量的关键潜在因素。大量研究表明,卵巢的发育主要依靠激素(皮质醇、促黄体素、促卵泡素)以及信号通路[哺乳动物雷帕霉素靶蛋白(m TOR)]调控。梅山猪相对于大白猪具有较高的产仔数,营养水平对梅山猪和大白猪的卵巢发育及调控模式存在差异。本文综述了梅山猪和大白猪卵巢对不同营养水平作用的应答差异,为未来研究提供理论依据。     

Arginine metabolism and its functions in growth,nutrient utilization,and immunonutrition of fish

Fish have limited ability in endogenous biosynthesis of arginine. Arginine is an indispensable amino acid for fish, and the arginine requirement varies with fish species and fish size. Recent studies on fish have demonstrated that arginine influences nutrient metabolism, stimulates insulin release, is involved in nonspecific immune responses and antioxidant responses, and elevates disease resistance. Specifically, arginine can regulate energy homeostasis via modulating the adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) pathway, and also regulate protein synthesis via activating the target of rapamycin (TOR) signaling pathway. The present article reviews pertinent knowledge of arginine in fish, including dietary quantitative requirements, endogenous anabolism and catabolism, regulation of the endocrine and metabolic systems, and immune-regulatory functions under pathogenic challenge. Our findings showed that further data about the distribution of arginine after intake into specific cells, its sub-cellular sensor to initiate downstream signaling pathways, and its effects on fish mucosal immunity, especially the adaptive immune response against pathogenic infection in different species, are urgently needed.     

Crop milk protein is synthesised following activation of the IRS1/Akt/TOR signalling pathway in the domestic pigeon (Columba livia)

1. The experiment was conducted to study whether insulin receptor substance 1 (IRS1) / Protein kinase B (Akt)/target of the rapamycin (TOR) signalling pathway activation stimulates crop milk protein synthesis in the domestic pigeon (Columba livia).

2. Crop milk was collected from ten 1-d-old squabs and analysed for nutrient content. During the non-breeding period and the first day of lactation, blood samples were collected from 5 pairs of breeding pigeons and the levels of prolactin and insulin were determined.

3. Crop samples were collected from 5 pairs of breeders at d 14 and 16 of the incubation period and d 1, 3 and 7 of the lactation period. Crop samples were evaluated for changes in crop weight and thickness and changes in the expression patterns of IRS1/Akt/TOR signalling pathway–related proteins.

4. The results demonstrated that prolactin induces a gradual increase in the relative weight and thickness of the crop, with crops reaching a maximum size at the third day of lactation.

5. Pigeon crop milk contains 64.1% crude protein and 29.7% crude fat based on dry weight.

6. Serum prolactin and insulin levels in the lactation period were significantly higher than those in the non-breeding period. Compared with non-breeding pigeons, the expression of the phosphorylated IRS1 phosphorylated Akt, phosphorylated TOR, phosphorylated ribosomal protein S6 kinase, phosphorylated S6, phosphorylated eukaryotic initiation factor 4E binding protein 1 and eukaryotic initiation factor 4E were significantly up-regulated in the crop of pigeons in the lactation period.

7. In conclusion, prolactin might induce changes in crop tissue and form the physiological structure for crop milk synthesis. Furthermore, the synthesis of crop milk protein is regulated by activation of the IRS1/Akt/TOR signalling pathway.

     

Triennial Growth Symposium: important roles for L-glutamine in swine nutrition and production

L-Glutamine (Gln) has traditionally not been considered a nutrient needed in diets for livestock species or even mentioned in classic animal nutrition textbooks. This is due to previous technical difficulties in Gln analysis and the unsubstantiated assumption that animals can synthesize sufficient amounts of Gln to meet their needs. Consequently, the current (1998) version of NRC does not recommend dietary Gln requirements for swine. This lack of knowledge about Gln nutrition has contributed to suboptimal efficiency of global pig production. Because of recent advances in research, Gln is now known to be an abundant AA in physiological fluids and proteins and a key regulator of gene expression. Additionally, Gln can regulate cell signaling via the mammalian target of rapamycin pathway, adenosine monophosphate-activated protein kinase, extracellular signal-related kinase, Jun kinase, mitogen-activated protein kinase, and nitric oxide. The exquisite integration of Gln-dependent regulatory networks has profound effects on cell proliferation, differentiation, migration, metabolism, homeostasis, survival, and function. As a result of translating basic research into practice, dietary supplementation with 1% Gln maintains gut health and prevents intestinal dysfunction in low-birth-weight or early-weaned piglets while increasing their growth performance and survival. In addition, supplementing 1% Gln to a corn- and soybean-meal-based diet between d 90 and 114 of gestation ameliorates fetal growth retardation in gilts and reduces preweaning mortality of piglets. Furthermore, dietary supplementation with 1% Gln enhances milk production by lactating sows. Thus, adequate amounts of dietary Gln, a major nutrient, are necessary to support the maximum growth, development, and production performance of swine.     

Refeeding and insulin activate the AKT/p70S6 kinase pathway without affecting IRS1 tyrosine phosphorylation in chicken muscle

p70 S6 kinase (p70S6K) is a key enzyme involved in the control of protein synthesis. We have previously shown that this kinase is insulin sensitive in chicken muscle despite a relative insulin resistance in the early steps of insulin receptor signaling in this tissue, particularly with no change in tyrosine phosphorylation of the insulin receptor substrate 1 (IRS1). The aim of the present study is to further study the p70S6K pathway in chicken muscle. By analyzing in silico several kinases involved in the protein kinase B (PKB also called AKT)/target of rapamycin (TOR)/p70S6K pathway in the chicken, we showed that the amino acid sequence of the proteins exhibited a very high identity with their homologs in mammalian species and Drosophila. We investigated the regulation of these kinases in vivo or in vitro. Refeeding and insulin treatment significantly (P<0.05) increased the phosphorylation and/or activity of kinases upstream of p70S6K such as AKT and TOR. Similarly, refeeding and insulin increased the phosphorylation of p70S6K on key residues (i.e. T389, T229 and T421/S424) and the phosphorylation of a p70S6K downstream target, the ribosomal protein S6 (by 3-10-fold, P<0.05). Interestingly, we also showed an increase in the phosphorylation level of IRS1 on S632/S635, sites involved in insulin resistance. In conclusion, the AKT/TOR/p70S6K pathway is activated by refeeding and insulin injection, which might negatively regulate IRS1 tyrosine phosphorylation. These results indicate some particularities of the insulin signaling in chicken muscle and suggest the involvement of p70S6K in these features.     

Effect of nutrient density and energy to protein ratio on performance and carcase quality of small white turkeys

One thousand eight hundred Small White turkeys were fed diets of 3 nutrient densities, representing approximately 0, 30 and 90 g added fat/kg of diet, or a fourth treatment which provided increasing nutrient densities from 6 weeks of age to slaughter at 12, 13 and 14 weeks. Within each nutrient density, 4 energy to protein ratios were derived by reducing dietary protein. Each increment in nutrient density resulted in increased body weights and improved efficiency of food utilisation. Increasing energy to protein ratio resulted in linear decreases in body weights, food intake and efficiency of food utilisation. Carcase quality, as measured by carcase fat scores and percentage of grade A carcases, improved with each increment in nutrient density and declined with increasing energy to protein ratio. Progressively increasing nutrient density from 6 weeks of age resulted in body weights, efficiencies of food utilisation and carcase finishes intermediate between those of the medium and high density groups. Such a programme avoids the disadvantages of feeding high nutrient density diets through much of the growing cycle, while providing growth, efficiency of food utilisation and carcase grades approaching those produced by the full high nutrient density programme.     

哺乳动物胎盘营养感应研究进展

妊娠期间母体营养的改变会影响胎儿的生长发育,而胎盘是母体-胎儿间进行气体、营养和代谢物交流的重要枢纽,哺乳动物胎盘营养感应系统响应母体和胎儿营养信号的变化,保证母体健康和胎儿生长发育。鉴于胎盘营养感应系统对哺乳动物繁育的重要性,本文从胎盘营养感应和胎盘养分分配方面综述了哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)、磷酸腺苷活化蛋白激酶(AMP-activated protein kinase,AMPK)、氨基己糖(Hexosamine)信号通路、糖原合成酶3(glycogen synthase kinase,GSK-3)、胰岛素/胰岛素样生长因子(insulin/insulin-like growth factor signaling pathway,IIS)等信号通路及其对妊娠期养分响应和对胎儿发育的影响,以期为哺乳动物的繁育提供参考依据。     

BOARD-INVITED REVIEW: opportunities and challenges in using exogenous enzymes to improve nonruminant animal production

Diets fed to nonruminant animals are composed mainly of feed ingredients of plant origin. A variety of antinutritional factors such as phytin, nonstarch polysaccharides, and protease inhibitors may be present in these feed ingredients, which could limit nutrients that may be utilized by animals fed such diets. The primary nutrient utilization-limiting effect of phytin arises from the binding of 6 phosphate groups, thus making the P unavailable to the animal. The negative charges allow for formation of insoluble phytin-metal complexes with many divalent cations. Furthermore, phytin and protein can form binary complexes through electrostatic links of its charged phosphate groups with either the free amino group on AA on proteins or via formation of ternary complexes of phytin, Ca(2+), and protein. The form and extent of de novo formation of binary and ternary complexes of phytin and protein are likely to be important variables that influence the effectiveness of nutrient hydrolysis in plant-based diets. Nonstarch polysacharides reduce effective energy and nutrient utilization by nonruminant animals because of a lack of the enzymes needed for breaking down the complex cell wall structure that encapsulate other nutrients. Enzymes are used in nonruminant animal production to promote growth and efficiency of nutrient utilization and reduce nutrient excretion. The enzymes used include those that target phytin and nonstarch polysaccharides. Phytase improves growth and enhances P utilization, but positive effects on other nutrients are not always observed. Nonstarch polysaccharide-hydrolyzing enzymes are less consistent in their effects on growth and nutrient utilization, although they show promise and it is imperative to closely match both types and amounts of nonstarch polysaccharides with appropriate enzyme for beneficial effects. When used together with phytase, nonstarch polysaccharide-hydrolyzing enzymes may increase the accessibility of phytase to phytin encapsulated in cell walls. The future of enzymes in nonruminant animal production is promising and will likely include an understanding of the role of enzyme supplementation in promoting health as well as how enzymes may modulate gene functions. This review is an attempt to summarize current thinking in this area, provide some clarity in nomenclature and mechanisms, and suggest opportunities for expanded exploitation of this unique biotechnology.     

Mechanistic modeling of turkey growth response to genotype and nutrition

Along with the fast genetic improvement, nutritional and environmental effects on poultry growth performance have made it necessary to develop growth models that have the flexibility to adapt to different genotypes and growing conditions. A mechanistic simulation model of energy and nutrient utilization in growing turkeys is presented herein. The model consists of simulating the average homeorhetic and homeostatic regulations associated with the utilization of circulating glucose, fatty acid, AA, and acetyl-CoA for protein and lipid retention in carcass, viscera, and feathers in a turkey population. Homeorhesis plays a major role in the control of protein and lipid turnover for the definition of genetic potential and feed intake, whereas homeostasis adjusts growth rate through protein and lipid turnover rates and, therefore, BW gain and feed intake to the growing conditions. Also, homeostasis enables the maintenance of a dynamic balance state during all the growing period through the control of circulating nutrient concentration. The model was developed and calibrated with experimental data that described energy utilization in male and female growing turkeys. Then, the ability of the model to adapt to genotypes and to predict the average response of a turkey population to dietary energy was evaluated. Model calibration showed simulations of energy and nutrient utilization that fitted well with the experimental data because ME was satisfyingly partitioned into heat production and energy retention as protein and lipid, and nutrient intake accurately partitioned BW gain into carcass, viscera, and feathers. The evaluation of the model was also satisfactory because BW gain and feed-to-gain ratio were globally in accordance with the observations in different male and female genotypes, in spite of an overestimation of the feed-to-gain ratio during the first weeks of age. Model evaluation showed that the BW gain and feed intake response of growing turkeys to dietary energy was accurately predicted. The model can therefore be used in different growing conditions as it is capable of simulating the growth of different turkey genotypes fed under changing environmental and nutritional contexts.     

应用灰色关联度分析法评价放牧绵羊增重和羊毛生长的营养限制因素

本文应用灰色系统理论中的灰色关联度分析法,对影响放牧绵羊生产性能的主要营养限制因素进行了研究。关联度分析结果表明,饲粮粗蛋白质水平是影响绵羊体重变化的主要营养因素,饲粮代谢能的影响次之;影响育成母羊羊毛生长速度的主要营养因素是其干物质采食量;而成年母羊羊毛生长的营养限制因素是饲粮粗蛋白质水平。影响绵羊采食量的主要营养因素是饲粮代谢能浓度,其次是牧草质量。影响牧草消化率的主要营养因素是绵羊瘤胃发酵水平,其次是牧草中的木质素含量。