Department of Applied Ecology, North Carolina State University, 100 Eugene Brooks Avenue, Box 7617, Raleigh, NC, 27695, USA.
Department of Agriculture, Nutrition, and Food Systems, University of New Hampshire, Durham, NH, USA.
BMC Genomics. 2024 Jun 10;25(1):580. doi: 10.1186/s12864-024-10325-y.
Understanding growth regulatory pathways is important in aquaculture, fisheries, and vertebrate physiology generally. Machine learning pattern recognition and sensitivity analysis were employed to examine metabolomic small molecule profiles and transcriptomic gene expression data generated from liver and white skeletal muscle of hybrid striped bass (white bass Morone chrysops x striped bass M. saxatilis) representative of the top and bottom 10 % by body size of a production cohort.
Larger fish (good-growth) had significantly greater weight, total length, hepatosomatic index, and specific growth rate compared to smaller fish (poor-growth) and also had significantly more muscle fibers of smaller diameter (≤ 20 µm diameter), indicating active hyperplasia. Differences in metabolomic pathways included enhanced energetics (glycolysis, citric acid cycle) and amino acid metabolism in good-growth fish, and enhanced stress, muscle inflammation (cortisol, eicosanoids) and dysfunctional liver cholesterol metabolism in poor-growth fish. The majority of gene transcripts identified as differentially expressed between groups were down-regulated in good-growth fish. Several molecules associated with important growth-regulatory pathways were up-regulated in muscle of fish that grew poorly: growth factors including agt and agtr2 (angiotensins), nicotinic acid (which stimulates growth hormone production), gadd45b, rgl1, zfp36, cebpb, and hmgb1; insulin-like growth factor signaling (igfbp1 and igf1); cytokine signaling (socs3, cxcr4); cell signaling (rgs13, rundc3a), and differentiation (rhou, mmp17, cd22, msi1); mitochondrial uncoupling proteins (ucp3, ucp2); and regulators of lipid metabolism (apoa1, ldlr). Growth factors pttg1, egfr, myc, notch1, and sirt1 were notably up-regulated in muscle of good-growing fish.
A combinatorial pathway analysis using metabolomic and transcriptomic data collectively suggested promotion of cell signaling, proliferation, and differentiation in muscle of good-growth fish, whereas muscle inflammation and apoptosis was observed in poor-growth fish, along with elevated cortisol (an anti-inflammatory hormone), perhaps related to muscle wasting, hypertrophy, and inferior growth. These findings provide important biomarkers and mechanisms by which growth is regulated in fishes and other vertebrates as well.
了解生长调控途径在水产养殖、渔业和脊椎动物生理学中都很重要。本研究采用机器学习模式识别和敏感性分析,研究了杂交条纹鲈(白鲈 Morone chrysops x 条纹鲈 M. saxatilis)肝脏和白色骨骼肌的代谢组小分子谱和转录组基因表达数据,这些鱼代表了一个生产批次中体型最大和最小的前 10%。
与体型较小的鱼(生长不良)相比,体型较大的鱼(生长良好)体重、全长、肝体比和特定生长率显著更高,肌肉纤维直径也显著更小(≤20 µm),表明其处于活跃的增生状态。代谢途径的差异包括生长良好的鱼中增强的能量代谢(糖酵解、柠檬酸循环)和氨基酸代谢,以及生长不良的鱼中增强的应激、肌肉炎症(皮质醇、类花生酸)和肝功能胆固醇代谢障碍。在两组间差异表达的大多数基因转录本在生长良好的鱼中下调。一些与重要生长调控途径相关的分子在生长不良的鱼肌肉中上调:生长因子包括 agt 和 agtr2(血管紧张素)、烟酸(刺激生长激素产生)、gadd45b、rgl1、zfp36、cepbp 和 hmgb1;胰岛素样生长因子信号(igfbp1 和 igf1);细胞因子信号(socs3、cxcr4);细胞信号(rgs13、rundc3a)和分化(rhou、mmp17、cd22、msi1);线粒体解偶联蛋白(ucp3、ucp2);和脂质代谢调节剂(apoa1、ldlr)。生长因子 pttg1、egfr、myc、notch1 和 sirt1 在生长良好的鱼肌肉中显著上调。
使用代谢组学和转录组学数据的组合途径分析表明,生长良好的鱼肌肉中细胞信号、增殖和分化得到促进,而生长不良的鱼肌肉中观察到肌肉炎症和细胞凋亡,同时皮质醇(一种抗炎激素)升高,可能与肌肉消耗、肥大和生长不良有关。这些发现为鱼类和其他脊椎动物的生长调控提供了重要的生物标志物和机制。