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首页> 外文期刊>Frontiers in Cell and Developmental Biology >Integrated Metabolomics and Lipidomics Analysis Reveal Remodeling of Lipid Metabolism and Amino Acid Metabolism in Glucagon Receptor–Deficient Zebrafish
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Integrated Metabolomics and Lipidomics Analysis Reveal Remodeling of Lipid Metabolism and Amino Acid Metabolism in Glucagon Receptor–Deficient Zebrafish

机译：综合的代谢组和脂质体分析显示胰高血糖素受体斑马鱼中脂质代谢和氨基酸代谢的重塑

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The glucagon receptor (GCGR) is activated by glucagon and is essential for glucose, amino acid and lipid metabolism of animals. GCGR blockade has been demonstrated to induce hypoglycemia, hyperaminoacidemia, hyperglucagonemia, decreased adiposity, hepatosteatosis and pancreatic α cells hyperplasia in organisms. However, the mechanism of how GCGR regulates these physiological functions is not yet very clear. In our previous study, we revealed that GCGR regulated metabolic network at transcriptional level by RNA-seq using GCGR mutant zebrafish (gcgr-/-). Here, we further performed whole-organism metabolomics and lipidomics profiling on wild type and gcgr-/- zebrafish to study the changes of metabolites. We found 107 significantly different metabolites from metabolomics analysis and 87 significantly different lipids from lipidomics analysis. Chemical substance classification and pathway analysis integrated with transcriptomics data both revealed that amino acid metabolism and lipid metabolism were remodeled in gcgr-deficient zebrafish. Similar to other studies, our study showed that gcgr-/- zebrafish exhibited decreased ureagenesis and impaired cholesterol metabolism. More interestingly, we found that the glycerophospholipid metabolism was disrupted, the arachidonic acid metabolism was up-regulated, and the tryptophan metabolism pathway was down-regulated in gcgr-/- zebrafish. Based on the omics data, we further validated our findings by revealing that gcgr-/- zebrafish exhibited dampened melatonin diel rhythmicity and increased locomotor activity. These global omics data provide us a better understanding about the role of GCGR in regulating metabolic network and new insight into GCGR physiological functions.
机译：胰高血糖素受体（GCGR）由胰高血糖素激活，对动物的葡萄糖，氨基酸和脂质代谢至关重要。已经证明了GCGR阻断，以诱导低血糖，高亚氨基葡萄糖血症，过糖体，降低肥胖，肝胃病和胰腺α细胞α细胞增生。但是，GCGR如何调节这些生理功能的机制尚不清楚。在我们以前的研究中，我们透露，GCGR使用GCGR突变体斑马鱼（GCGR - / - ）通过RNA-SEQ进行转录水平的代谢网络。在这里，我们进一步对野生型和GCGR - / - 斑马鱼进行了全体生物体代谢组科和脂质化学学分析，以研究代谢物的变化。我们发现107种来自代谢组科分析的显着不同的代谢物，87种来自脂质谱系分析的显着不同的脂质。与转录组织数据相结合的化学物质分类和途径分析显示，在GCGR缺陷型斑马鱼中改造氨基酸代谢和脂质代谢。与其他研究类似，我们的研究表明，GCGR - / - 斑马鱼表现出降低的尿素作用和胆固醇代谢受损。更有意义的是，我们发现甘油磷脂代谢被破坏，诱导甘偕酸代谢进行上调，并且在GCGR - / - 斑马鱼中对色氨酸代谢途径进行了下调。基于OMICS数据，我们进一步通过揭示GCGR - / - 斑马鱼展示了抑制褪黑激素Diel节律性和增加的运动活动来验证了我们的研究结果。这些全球OMICS数据提供了更好地了解GCGR在调节代谢网络和新洞察力对GCGR生理功能的新洞察中的作用。

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