Clofibrate enhancement of mitochondrial carnitine transport system of rat liver and augmentation of liver carnitine and gamma-butyrobetaine hydroxylase activity by thyroxine. 1980

S V Pande, and R Parvin

The possibilities that the hypotriglyceridemic effect of clofibrate involves activation of carnitine-dependent oxidation of fatty acids in liver and that this may be partially mediated through thyroxine have been examined. 0.25% clofibrate in diet for 10-15 days, was found to increase carnitine 3-fold in livers of male as well as female rats. Liver carnitine was nearly doubled by L-thyroxine, 6 mg/kg of diet fed for 10 days, and so was the activity of gamma-butyrobetaine hydroxylase. Clofibrate decreased carnitine in heart and urine; thyroxine did not affect these parameters but increased serum carnitine by 26%. Clofibrate feeding doubled the concentration of hepatic long-chain acyl(-)carnitine, mitochondrial carnitine, and the rate of mitochondrial carnitine-acylcarnitine translocase reaction, and enhanced acetoacetate production in liver homogenates as well as mitochondrial oxidation of palmitoylcarnitine in the presence of malonate. The ratio of esterified to free carnitine in urine and serum was also increased by clofibrate. These results suggest that clofibrate and thyroxine may exert their hypotriglyceridemic effect, in part, through the activation of carnitine-mediated transport of fatty acids in liver mitochondria.

UI MeSH Term Description Entries
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
D002331 Carnitine A constituent of STRIATED MUSCLE and LIVER. It is an amino acid derivative and an essential cofactor for fatty acid metabolism. Bicarnesine,L-Carnitine,Levocarnitine,Vitamin BT,L Carnitine
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
D005260 Female Females
D006899 Mixed Function Oxygenases Widely distributed enzymes that carry out oxidation-reduction reactions in which one atom of the oxygen molecule is incorporated into the organic substrate; the other oxygen atom is reduced and combined with hydrogen ions to form water. They are also known as monooxygenases or hydroxylases. These reactions require two substrates as reductants for each of the two oxygen atoms. There are different classes of monooxygenases depending on the type of hydrogen-providing cosubstrate (COENZYMES) required in the mixed-function oxidation. Hydroxylase,Hydroxylases,Mixed Function Oxidase,Mixed Function Oxygenase,Monooxygenase,Monooxygenases,Mixed Function Oxidases,Function Oxidase, Mixed,Function Oxygenase, Mixed,Oxidase, Mixed Function,Oxidases, Mixed Function,Oxygenase, Mixed Function,Oxygenases, Mixed Function
D000090 Acetoacetates Salts and derivatives of acetoacetic acid.
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001692 Biological Transport The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments. Transport, Biological,Biologic Transport,Transport, Biologic
D013268 Stimulation, Chemical The increase in a measurable parameter of a PHYSIOLOGICAL PROCESS, including cellular, microbial, and plant; immunological, cardiovascular, respiratory, reproductive, urinary, digestive, neural, musculoskeletal, ocular, and skin physiological processes; or METABOLIC PROCESS, including enzymatic and other pharmacological processes, by a drug or other chemical. Chemical Stimulation,Chemical Stimulations,Stimulations, Chemical

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