Effects of fenofibrate treatment on fatty acid oxidation in liver mitochondria of obese Zucker rats.
Obese Zucker rats were dosed orally for one week with fenofibrate (100 mg/kg). Liver weights of treated rats as expressed as percent of body weight were slightly increased, while protein, DNA and lipid contents were unaffected per g of liver or increased when expressed in whole liver. Compared with the control animals, activities of fatty acid oxidase, of the peroxisomal fatty acid-oxidizing system and of catalase were markedly increased by fenofibrate both per g of liver and per total liver, while urate oxidase activity was unchanged when expressed per g of liver. The activity of monoamine oxidase and that of cytochrome c oxidase used as marker enzymes for mitochondria were increased only when expressed per total liver. However, fenofibrate treatment induced a pronounced increase in the activities of mitochondrial palmitoyl-CoA dehydrogenase and carnitine acyltransferases, particularly carnitine acetyltransferase. Fenofibrate also caused a significant increase of carnitine content in liver and hepatic mitochondria. The greatest observed increases were in free carnitine and in the rate of carnitine-dependent oleate oxidation, which might be favoured in vivo by a lesser sensitivity of CPT-I to a malonyl-CoA inhibitory effect. The present results suggest that fenofibrate treatment induces increased hepatic mitochondrial beta-oxidation in obese Zucker rats.
Henninger
C
C
Laboratoire de Physiologie Animale et de la Nutrition, U.A. CNRS 273, Faculté des Sciences Mirande, Dijon, France.
Clouet
P
P
Cao Danh
H
H
Pascal
M
M
Bezard
J
J
D000818:Animals; D002331:Carnitine / Q000032:analysis; D002332:Carnitine O-Acetyltransferase / Q000032:analysis; D005227:Fatty Acids / Q000378:metabolism*; D011345:Fenofibrate / Q000494:pharmacology*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008297:Male; D008316:Malonyl Coenzyme A / Q000032:analysis; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D010171:Palmitoyl Coenzyme A / Q000378:metabolism; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D011924:Rats, Zucker
D005227:Fatty Acids; D000960:Hypolipidemic Agents; D011422:Propionates; D010171:Palmitoyl Coenzyme A; D008316:Malonyl Coenzyme A; D002332:Carnitine O-Acetyltransferase; D002331:Carnitine; D011345:Fenofibrate