Inhibited carnitine synthesis causes systemic alteration of nutrient metabolism in zebrafish.

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dc.contributor.authorJia-Min, Li
dc.contributor.authorLing-Yu, Li
dc.contributor.authorXuan, Qin
dc.contributor.authorPascal, Degrace
dc.contributor.authorLaurent Demizieux, Demizieux
dc.contributor.authorSamwel Mchele Limbu
dc.contributor.authorXin, Wang
dc.contributor.authorMei-Ling, Zhang
dc.contributor.authorDong-Liang, Li
dc.contributor.authorZhen-Yu Du, Du
dc.date.accessioned2019-05-07T13:06:05Z
dc.date.available2019-05-07T13:06:05Z
dc.date.issued2018-05-09
dc.description.abstractImpaired 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.en_US
dc.description.sponsorshipNational Basic Research Program of China (973 Program 2014CB138603) and National Natural Science Fund (31772859 and 31472290).en_US
dc.identifier.citationFrontiers in Physiologyen_US
dc.identifier.doihttps://doi.org/10.3389/fphys.2018.00509
dc.identifier.urihttp://hdl.handle.net/20.500.11810/5223
dc.subjectlow carnitine zebrafishen_US
dc.subjectmildronateen_US
dc.subjectFA β-oxidationen_US
dc.subjectdyslipidemiaen_US
dc.subjectmetabolismen_US
dc.titleInhibited carnitine synthesis causes systemic alteration of nutrient metabolism in zebrafish.en_US
dc.typeJournal Article, Peer Revieweden_US
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