Abstract
Uridine, a pyrimidine nucleoside, can modulate liver lipid metabolism although its specific acting targets have not been identified. Using mice with fenofibrate-induced fatty liver as a model system, the effects of uridine on liver lipid metabolism are examined. At a daily dosage of 400 mg/kg, fenofibrate treatment causes reduction of liver NAD(+)/NADH ratio, induces hyper-acetylation of peroxisomal bifunctional enzyme (ECHD) and acyl-CoA oxidase 1 (ACOX1), and induces excessive accumulation of long chain fatty acids (LCFA) and very long chain fatty acids (VLCFA). Uridine co-administration at a daily dosage of 400 mg/kg raises NAD(+)/NADH ratio, inhibits fenofibrate-induced hyper-acetylation of ECHD, ACOX1, and reduces accumulation of LCFA and VLCFA. Our data indicates a therapeutic potential for uridine co-administration to prevent fenofibrate-induced fatty liver.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Acyl-CoA Oxidase / genetics
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Acyl-CoA Oxidase / metabolism
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Animals
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Biological Transport / drug effects
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Fatty Acids / metabolism
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Fatty Liver / chemically induced
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Fatty Liver / enzymology
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Fatty Liver / pathology
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Fatty Liver / prevention & control*
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Fenofibrate / adverse effects*
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Gene Expression Regulation
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Hypolipidemic Agents / adverse effects*
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Lipid Metabolism / drug effects
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Liver / drug effects
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Liver / enzymology
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Liver / pathology
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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NAD / metabolism
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Oxidation-Reduction / drug effects
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Peroxisomal Bifunctional Enzyme / genetics
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Peroxisomal Bifunctional Enzyme / metabolism
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Protective Agents / pharmacology*
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Uridine / pharmacology*
Substances
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Fatty Acids
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Hypolipidemic Agents
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Protective Agents
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NAD
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Acyl-CoA Oxidase
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Peroxisomal Bifunctional Enzyme
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Fenofibrate
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Uridine