6533b838fe1ef96bd12a47f7
RESEARCH PRODUCT
Hypolipidaemic effects of fenofibrate are not altered by mildronate-mediated normalization of carnitine concentration in rat liver.
Jean DemarquoyFrédéric BeauseigneurMarcelline TsokoPierre ClouetJoseph Grestisubject
DrugMalemedicine.medical_specialtymedia_common.quotation_subjectBlood lipidsKetone BodiesBiochemistrychemistry.chemical_compoundFenofibrateInternal medicineCarnitinemedicineAnimalsCarnitineRats WistarMuscle SkeletalBeta oxidationPhospholipidsTriglyceridesmedia_commonHypolipidemic AgentsFenofibrateTriglycerideChemistryMyocardiumGeneral MedicinePeroxisomeRatsEndocrinologyCholesterolBiochemistryLiverKetone bodiesmedicine.drugMethylhydrazinesdescription
The five-fold higher carnitine content in the liver of fenofibrate-treated rats addresses the question about the possible role of this enhancement in the hypolipidaemic effect of the drug and the underlying mechanisms. When fenofibrate was administered with mildronate (a gamma-butyrobetaine hydroxylase inhibitor) in suitable amount, the content in carnitine was found to be normalized in liver. However, triglyceride contents of liver and serum were then at least as low as in rats treated by fenofibrate only. When carnitine concentration was lowered by mildronate to the third of the normal value, a marked increase in triglycerides occurred both in liver and serum, while the five-fold increase in carnitine due to fenofibrate enhanced blood ketone body concentration with no effect on liver and serum triglycerides. Data suggest that the normal carnitine concentration is largely sufficient to meet the usual requirement for carnitine palmitoyltransferase I activity (CPT I). In rat liver, increase in mitochondrial CPT I activity and in peroxisomal fatty acid oxidation may constitute part of the hypolipidaemic effect of fenofibrate.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 1999-01-20 | Biochimie |