Effect of clofibrate and gemfibrozil on the activities of mitochondrial carnitine acyltransferases in rat liver. Dose--response relations. 1979

M T Kähönen, and R H Ylikahri

The effects of different doses of clofibrate and gemfibrozil on liver size, serum triglyceride concentration and the activities of hepatic mitochondrial alpha-glycerophosphate dehydrogenase (alpha-GPD) and carnitine acyltransferases were studied in male rats. Both clofibrate and gemfibrozil treatment effectively decreased the fructose-induced hypertriglyceridaemia and increased the liver to body weight ratio. Clofibrate treatment also induced an increase of many times in the activities of mitochondrial alpha-GPD and carnitine acyltransferases, the effect increasing with the dose used. The effect of gemfibrozil on the activities of the enzymes was significantly smaller. There was no correlation between the decrease in serum triglyceride concentration and the changes in the activities of the enzymes. Only clofibrate increased the rate of fatty acylcarnitine oxidation in isolated mitochondria. It is concluded that both drugs increased the size of the rat liver, but that only clofibrate influenced the mitochondrial enzyme activities of mitochondrial carnitine acyltransferases and the accelerated mitochondrial oxidation of fatty acids are not the mechanisms by which these drugs lower serum lipid levels.

UI MeSH Term Description Entries
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008297 Male Males
D008930 Mitochondria, Liver Mitochondria in hepatocytes. As in all mitochondria, there are an outer membrane and an inner membrane, together creating two separate mitochondrial compartments: the internal matrix space and a much narrower intermembrane space. In the liver mitochondrion, an estimated 67% of the total mitochondrial proteins is located in the matrix. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p343-4) Liver Mitochondria,Liver Mitochondrion,Mitochondrion, Liver
D009929 Organ Size The measurement of an organ in volume, mass, or heaviness. Organ Volume,Organ Weight,Size, Organ,Weight, Organ
D010421 Pentanoic Acids Straight-chain CARBOXYLIC ACIDS with the general formula C5H10O2. Acids, Pentanoic
D001835 Body Weight The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms. Body Weights,Weight, Body,Weights, Body
D002333 Carnitine Acyltransferases Acyltransferases in the inner mitochondrial membrane that catalyze the reversible transfer of acyl groups from acyl-CoA to L-carnitine and thereby mediate the transport of activated fatty acids through that membrane. EC 2.3.1. Acylcarnitine Translocase,Carnitine Translocase,Carnitine-Acetylcarnitine Translocase,Carnitine-Acylcarnitine Translocase,Acyltransferases, Carnitine,Carnitine Acetylcarnitine Translocase,Carnitine Acylcarnitine Translocase,Translocase, Acylcarnitine,Translocase, Carnitine,Translocase, Carnitine-Acetylcarnitine,Translocase, Carnitine-Acylcarnitine
D002994 Clofibrate A fibric acid derivative used in the treatment of HYPERLIPOPROTEINEMIA TYPE III and severe HYPERTRIGLYCERIDEMIA. (From Martindale, The Extra Pharmacopoeia, 30th ed, p986) Athromidin,Atromid,Atromid S,Clofibric Acid, Ethyl Ester,Ethyl Chlorophenoxyisobutyrate,Miscleron,Miskleron,Chlorophenoxyisobutyrate, Ethyl
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005632 Fructose A monosaccharide in sweet fruits and honey that is soluble in water, alcohol, or ether. It is used as a preservative and an intravenous infusion in parenteral feeding. Levulose,Apir Levulosa,Fleboplast Levulosa,Levulosa,Levulosa Baxter,Levulosa Braun,Levulosa Grifols,Levulosa Ibys,Levulosa Ife,Levulosa Mein,Levulosado Bieffe Medit,Levulosado Braun,Levulosado Vitulia,Plast Apyr Levulosa Mein,Levulosa, Apir,Levulosa, Fleboplast

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