Inhibited Carnitine Synthesis Causes Systemic Alteration of Nutrient Metabolism in Zebrafish.
Inhibited Carnitine Synthesis Causes Systemic Alteration of Nutrient Metabolism in Zebrafish.
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肉碱合成受到抑制导致斑马鱼营养代谢的系统性改变
DOI：
10.3389/fphys.2018.00509
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发表时间：
2018
影响因子：
4
通讯作者：
Du ZY
中科院分区：
文献类型：
--
作者：
Li JM;Li LY;Qin X;Degrace P;Demizieux L;Limbu SM;Wang X;Zhang ML;Li DL;Du ZY
线粒体脂肪酸β - 氧化受损与许多代谢综合征相关，并且线粒体功能障碍的哺乳动物模型的代谢特征也已得到深入研究。然而，线粒体脂肪酸β - 氧化受损对硬骨鱼全身代谢的影响从未被研究过。在本研究中，我们通过用米屈肼（一种特异性的肉碱合成抑制剂，按0.05%体重/天的剂量）喂养斑马鱼7周建立了一个低肉碱斑马鱼模型，并测量了包括肉碱和甘油三酯（TG）浓度、脂肪酸（FA）β - 氧化能力以及脂质、葡萄糖和蛋白质代谢的其他分子和生化检测在内的全身营养代谢变化。结果表明，米屈肼显著降低了肝脏中的肉碱浓度，但对肌肉没有影响。在米屈肼处理的鱼中，肝脏TG浓度增加了50%以上。米屈肼降低了肝脏线粒体β - 氧化的效率，增加了与FAβ - 氧化和脂解相关基因的肝脏mRNA表达，并降低了脂肪生成基因的表达。米屈肼降低了全身糖原含量，提高了葡萄糖代谢率，并上调了葡萄糖摄取和糖酵解基因的表达。米屈肼还增加了全身蛋白质含量和雷帕霉素靶蛋白（mTOR）的肝脏mRNA表达，并降低了一个蛋白质分解代谢相关基因的表达。肝脏而非肌肉是米屈肼作用的主要靶器官。简而言之，米屈肼诱导的斑马鱼肝脏肉碱合成抑制导致线粒体FAβ - 氧化效率降低、脂质积累增加以及葡萄糖和蛋白质代谢改变。这揭示了线粒体脂肪酸β - 氧化在鱼类营养代谢中的关键作用，并且这种低肉碱斑马鱼模型也可作为未来代谢研究的一种新型鱼类模型。
Impaired mitochondrial fatty acid β-oxidation has been correlated with many metabolic syndromes, and the metabolic characteristics of the mammalian models of mitochondrial dysfunction have also been intensively studied. However, the effects of the impaired mitochondrial fatty acid β-oxidation on systemic metabolism in teleost have never been investigated. In the present study, we established a low-carnitine zebrafish model by feeding fish with mildronate as a specific carnitine synthesis inhibitor [0.05% body weight (BW)/d] for 7 weeks, and the systemically changed nutrient metabolism, including carnitine and triglyceride (TG) concentrations, fatty acid (FA) β-oxidation capability, and other molecular and biochemical assays of lipid, glucose, and protein metabolism, were measured. The results indicated that mildronate markedly decreased hepatic carnitine concentrations while it had no effect in muscle. Liver TG concentrations increased by more than 50% in mildronate-treated fish. Mildronate decreased the efficiency of liver mitochondrial β-oxidation, increased the hepatic mRNA expression of genes related to FA β-oxidation and lipolysis, and decreased the expression of lipogenesis genes. Mildronate decreased whole body glycogen content, increased glucose metabolism rate, and upregulated the expression of glucose uptake and glycolysis genes. Mildronate also increased whole body protein content and hepatic mRNA expression of mechanistic target of rapamycin (mtor), and decreased the expression of a protein catabolism-related gene. Liver, rather than muscle, was the primary organ targeted by mildronate. In short, mildronate-induced hepatic inhibited carnitine synthesis in zebrafish caused decreased mitochondrial FA β-oxidation efficiency, greater lipid accumulation, and altered glucose and protein metabolism. This reveals the key roles of mitochondrial fatty acid β-oxidation in nutrient metabolism in fish, and this low-carnitine zebrafish model could also be used as a novel fish model for future metabolism studies.
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影响因子：
3.6
作者：
Du, ZY;Clouet, P;Liu, YJ
通讯作者：
Liu, YJ
草食性草鱼（Ctenopharyngodon idella）高水平利用不同膳食脂质来源：与肝脏脂肪酸氧化相关的机制
影响因子：
3.5
作者：
Du, Z. Y.;Clouet, P.;Liu, Y. J.
通讯作者：
Liu, Y. J.
DOI：
10.1016/j.bbalip.2010.01.002
发表时间：
2010-04-01
影响因子：
4.8
作者：
Du, Zhen-Yu;Ma, Tao;Madsen, Lise
通讯作者：
Madsen, Lise
影响因子：
4.5
作者：
Betancor, M. B.;Sprague, M.;Sayanova, O.;Usher, S.;Campbell, P. J.;Napier, J. A.;Caballero, M. J.;Tocher, D. R.
通讯作者：
Tocher, D. R.
影响因子：
3
作者：
Liepinsh, Edgars;Vilskersts, Reinis;Dambrova, Maija
通讯作者：
Dambrova, Maija