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木胸肌(未)受影响的肉鸡的肌肉代谢组学特征:富含量子蓝植酸酶日粮的影响。

Muscle Metabolome Profiles in Woody Breast-(un)Affected Broilers: Effects of Quantum Blue Phytase-Enriched Diet.

作者信息

Greene Elizabeth, Cauble Reagan, Dhamad Ahmed E, Kidd Michael T, Kong Byungwhi, Howard Sara M, Castro Hector F, Campagna Shawn R, Bedford Mike, Dridi Sami

机构信息

Center of Excellence for Poultry Science, University of Arkansas, Fayetteville, AR, United States.

Department of Animal Sciences, University of Arkansas, Fayetteville, AR, United States.

出版信息

Front Vet Sci. 2020 Aug 4;7:458. doi: 10.3389/fvets.2020.00458. eCollection 2020.

Abstract

Woody breast (WB) myopathy is significantly impacting modern broilers and is imposing a huge economic burden on the poultry industry worldwide. Yet, its etiology is not fully defined. In a previous study, we have shown that hypoxia and the activation of its upstream mediators (AKT/PI3K/mTOR) played a key role in WB myopathy, and supplementation of quantum blue (QB) can help to reduce WB severity via modulation of hypoxia-related pathways. To gain further insights, we undertook here a metabolomics approach to identify key metabolite signatures and outline their most enriched biological functions. Ultra performance liquid chromatography coupled with high resolution mass spectrometry (UPLC-HRMS) identified a total of 108 known metabolites. Of these, mean intensity differences at < 0.05 were found in 60 metabolites with 42 higher and 18 lower in WB-affected compared to unaffected muscles. Multivariate analysis and Partial Least Squares Discriminant analysis (PLS-DA) scores plot displayed different clusters when comparing metabolites profile from affected and unaffected tissues and from moderate (MOD) and severe (SEV) WB muscles indicating that unique metabolite profiles are present for the WB-affected and unaffected muscles. To gain biologically related molecule networks, a stringent pathway analyses was conducted using IPA knowledge-base. The top 10 canonical pathways generated, using a fold-change -1.5 and 1.5 cutoff, with the 50 differentially abundant-metabolites were purine nucleotide degradation and biosynthesis, sirtuin signaling pathway, citrulline-nitric oxide cycle, salvage pathways of pyrimidine DNA, IL-1 signaling, iNOS, Angiogenesis, PI3K/AKT signaling, and oxidative phosphorylation. The top altered bio-functions in term of molecular and cellular functions in WB-affected tissues included cellular development, cellular growth and proliferation, cellular death and survival, small molecular biochemistry, inflammatory response, free radical scavenging, cell signaling and cell-to-cell interaction, cell cycles, and lipid, carbohydrate, amino acid, and nucleic acid metabolisms. The top disorder functions identified were organismal injury and abnormalities, cancer, skeletal and muscular disorders, connective tissue disorders, and inflammatory diseases. Breast tissues from birds fed with high dose (2,000 FTU) of QB phytase exhibited 22 metabolites with significantly different levels compared to the control group with a clear cluster using PLS-DA analysis. Of these 22 metabolites, 9 were differentially abundant between WB-affected and unaffected muscles. Taken together, this study determined many metabolic signatures and disordered pathways, which could be regarded as new routes for discovering potential mechanisms of WB myopathy.

摘要

木质化鸡胸(WB)肌病对现代肉鸡产生了重大影响,给全球家禽业带来了巨大的经济负担。然而,其病因尚未完全明确。在先前的一项研究中,我们已经表明缺氧及其上游介质(AKT/PI3K/mTOR)的激活在WB肌病中起关键作用,补充量子蓝(QB)可以通过调节缺氧相关途径来帮助减轻WB的严重程度。为了进一步深入了解,我们在这里采用代谢组学方法来识别关键代谢物特征,并概述其最丰富的生物学功能。超高效液相色谱与高分辨率质谱联用(UPLC-HRMS)共鉴定出108种已知代谢物。其中,与未受影响的肌肉相比,在60种代谢物中发现平均强度差异<0.05,其中42种在受WB影响的肌肉中较高,18种较低。多变量分析和偏最小二乘判别分析(PLS-DA)得分图显示,在比较受影响和未受影响组织以及中度(MOD)和重度(SEV)WB肌肉的代谢物谱时呈现出不同的聚类,表明受WB影响和未受影响的肌肉存在独特的代谢物谱。为了获得生物学相关的分子网络,使用IPA知识库进行了严格的通路分析。使用-1.5和1.5的变化倍数截止值生成的前10条典型通路,以及50种差异丰富的代谢物,分别是嘌呤核苷酸降解和生物合成、沉默调节蛋白信号通路、瓜氨酸-一氧化氮循环、嘧啶DNA的补救途径、IL-1信号通路、诱导型一氧化氮合酶、血管生成、PI3K/AKT信号通路和氧化磷酸化。在受WB影响的组织中,就分子和细胞功能而言,变化最大的生物功能包括细胞发育、细胞生长和增殖、细胞死亡和存活、小分子生物化学、炎症反应、自由基清除、细胞信号传导和细胞间相互作用、细胞周期以及脂质、碳水化合物、氨基酸和核酸代谢。确定的最主要的功能紊乱是机体损伤和异常、癌症、骨骼和肌肉疾病、结缔组织疾病以及炎症性疾病。用高剂量(2000 FTU)QB植酸酶喂养的鸡的胸肌组织与对照组相比,有22种代谢物水平有显著差异,PLS-DA分析显示有明显的聚类。在这22种代谢物中,有9种在受WB影响和未受影响的肌肉之间差异丰富。综上所述,本研究确定了许多代谢特征和紊乱的途径,可被视为发现WB肌病潜在机制的新途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4efd/7417653/7e844cbb9d78/fvets-07-00458-g0001.jpg

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