Stimulation of fatty acid utilization by sodium clofibrate in rat and monkey hepatocytes

Capuzzi, David M.; Intenzo, Charles; Lackman, Richard D.; Whereat, Arthur F.; Scott, Dana Marie

doi:10.1016/0006-2952(83)90226-5

Cited by 20 publications

(3 citation statements)

References 42 publications

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“…In addition to the ~)croxisomal changes. incr-cased ability of mitochondria to o x i d i~c fhtty acids also has been reported (25)(26)(27). Ilicts containing 0.…”

Section: Administrution To Mice Oj'u 05% Chlorpromuzine-c'ontuiningmentioning

confidence: 69%

Peroxisomal Proliferation in Heart and Liver of Mice Receiving Chlorpromazine, Ethyl 2(5(4-Chlorophenyl)Pentyl) Oxiran-2-Carboxylic Acid or High Fat Diet: A Biochemical and Morphometrical Comparative Study

et al. 1987

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Experiments with chlorpromazine, an inhibitor of peroxisomal carnitine octanoyltransferase, have led to the proposal that peroxisomal 0-oxidation which was depressed by the phenothiazine in isolated hepatocytes (1) was dependent on carnitine (2). On the other hand, the inhibition of both cytochrome c oxidase and chlorpromazine palmitoyltransferase activities (2) were proposed as the cause of the reduced ketone body formation from long-

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“…In addition to the ~)croxisomal changes. incr-cased ability of mitochondria to o x i d i~c fhtty acids also has been reported (25)(26)(27). Ilicts containing 0.…”

Section: Administrution To Mice Oj'u 05% Chlorpromuzine-c'ontuiningmentioning

confidence: 69%

Peroxisomal Proliferation in Heart and Liver of Mice Receiving Chlorpromazine, Ethyl 2(5(4-Chlorophenyl)Pentyl) Oxiran-2-Carboxylic Acid or High Fat Diet: A Biochemical and Morphometrical Comparative Study

et al. 1987

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“…We have reported that clofibrate, tiadenol and niadenate, all hypolipidemic drugs, as well as the potent tumour promoter 12-0-tetradecanoylphorbol-13-acetate, induced differentiation of the mouse embryo fibroblast line C3H/10T 1/2 C18 cells to adipocytes (14). The earliest change seen in rat hepatocytes treated with clofibrate (21,22) and high fat concentration (22) are an increased synthesis of triglyceride and increased peroxisomal /3-oxidation. Accumulation of lipid may be a common 'trigger' for peroxisome proliferation accompanied by an increase of the peroxisomal /3-oxidation enzyme system.…”

Section: Discussionmentioning

confidence: 99%

Effect of choline-deficiency and methotrexate administration on peroxisomal β-oxidation, palmitoyl-CoA hydrolase activity and the glutathione content in rat liver

Berge¹,

Aarsæther²,

Aarsland³

et al. 1988

Carcinogenesis

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Hepatic metabolism of long-chain fatty acids was studied in male rats fed a defined choline-deficient (CD) diet with and without choline and after methotrexate (MTX) administration. Peroxisomal beta-oxidation was increased approximately 4-fold in the peroxisome-enriched fraction of CD-fed animals, whereas the catalase activity was increased 1.3-fold. The urate oxidase activity was marginally affected. The CD-fed rats also revealed elevated capacity for hydrolysis of palmitoyl-CoA in the cytosolic fraction (2.0-fold), whereas the microsomal palmitoyl-CoA hydrolase activity was decreased. Notably, the increased peroxisomal beta-oxidation, the catalase activity and palmitoyl-CoA hydrolase activities (the membrane-bounded and cytosolic) were almost fully prevented by adding choline to the CD-diet. Thus, the change in these enzyme activities appears to be a consequence of a choline-deficiency provoked by the CD diet. MTX administration of normal fed rats (ND diet) had no effects on the peroxisomal beta-oxidation, catalase activity and urate oxidase activity. MTX treatment of the ND-fed animals, however, increased the mitochondrial palmitoyl-CoA hydrolase activity and decreased the microsomal enzyme activity. As choline-deficiency and MTX increased the hepatic lipid level, the overall results suggest that fat accumulation is not an 'induction signal' for increased peroxisomal beta-oxidation. The CD diet alone increased the reduced glutathione content in liver, whereas MTX did not significantly change this level. Whether the changes of H2O2-generating peroxisomal oxidation of long-chain fatty acids may be an important step in a chain of events, which eventually results in tumour formation by choline-deficiency, should be considered.

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“…We have recently demonstrated that preischernic perfusion with 0.08 mM nicotinic acid increased the incorporation of [I4c] palmitic acid into membrane pkospholipids, reduced the in$a:acellular P A level, and decreased plasma creatine kinase (CK) release during the reperfusion period (Datta et al 2986 For personal use only. stimulated activity of 1-acylglycemphosphorylcholine acyltransferase (Mawashima et al 1986) and the incorporation of fatty acids into triglycerides in isolated hepatocytes (Capuzzi et al 1983). These cellular events may also reduce the level of deleterious fatty acids and stimulate phospholipid synthesis which can reduce the myocardial injury that occurs during ischemia and reperfusion.…”

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confidence: 99%

Improved myocardial performance induced by dofibrate during reperfusion after acute myocardial infarction

Prasad

Clement²,

Otani³

et al. 1988

Can. J. Physiol. Pharmacol.

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The increase of cellular fatty acids appears to be one of the causes of the myocardial injury during ischemia and reperfusion. This study was designed to examine whether a hypolipidemic drug such as clofibrate can reduce the myocardial injury during ischemia and reperfusion. Clofibrate was fed to experimental pigs for 9 days. Isolated in situ hearts from both experimental and control pigs were subjected to 60 min of regional ischemia induced by occluding the left anterior descending coronary artery, followed by 60 min of global ischemia by hypothermic cardioplegic arrest and 60 min of reperfusion. The clofibrate feeding resulted in the better cardiac performance as judged by increased coronary blood flow, improved left ventricular function, and reduced myocardial injury as judged by creatine kinase release. Although the clofibrate-fed animals contained higher levels of thiobarbituric reactive materials, the free fatty acid levels of plasma and myocardium were much lower compared with control animals. The clofibrate feeding was also associated with increased peroxisomal catalase and beta-oxidation of fatty acids. These results suggest that decreased levels of free fatty acids in the plasma and the myocardium and increased catalase activity induced by antilipolytic therapy appear to provide beneficial effects to the myocardium during ischemia and reperfusion.

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Stimulation of fatty acid utilization by sodium clofibrate in rat and monkey hepatocytes

Cited by 20 publications

References 42 publications

Peroxisomal Proliferation in Heart and Liver of Mice Receiving Chlorpromazine, Ethyl 2(5(4-Chlorophenyl)Pentyl) Oxiran-2-Carboxylic Acid or High Fat Diet: A Biochemical and Morphometrical Comparative Study

Peroxisomal Proliferation in Heart and Liver of Mice Receiving Chlorpromazine, Ethyl 2(5(4-Chlorophenyl)Pentyl) Oxiran-2-Carboxylic Acid or High Fat Diet: A Biochemical and Morphometrical Comparative Study

Effect of choline-deficiency and methotrexate administration on peroxisomal β-oxidation, palmitoyl-CoA hydrolase activity and the glutathione content in rat liver

Improved myocardial performance induced by dofibrate during reperfusion after acute myocardial infarction

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