Fenofibrate prevents orotic acid--induced hepatic steatosis in rats.
The experiments performed in this report were designed to investigate the mechanisms involved in the metabolic alterations associated with orotic acid-induced hepatic steatosis and the effect of fenofibrate, a stimulant of peroxisome proliferators-activated receptor alpha (PPARalpha), on these alterations. Male Wistar rats were divided into three experimental groups: 1) fed a balanced diet (C); 2) fed a balanced diet supplemented with 1% orotic acid (OA); 3) fed OA diet containing 100 mg.kg(-1) bw.day(-1) fenofibrate (OA+F), for 9 days. Administration of OA to rats induced significant increase in the hepatic total lipids content, marked microvesicular steatosis and decrease in plasma lipids concentrations compared to control group. Fenofibrate treatment prevented fatty liver induction, caused an additional reduction on plasma lipids concentrations and caused a 40% decrease in the lipogenic rate in adipose tissue. The results also showed a 40% increase in lipoprotein lipase (LPL) activity in adipose tissue from OA treated group and fenofibrate administration induced a 50% decrease in LPL activity. The liver mRNA expression of PPARalpha and ACO (acyl CoA oxidase) were 85% and 68% decreased in OA group when compared to control, respectively. Fenofibrate treatment increased the PPARalpha and ACO expressions whereas the CPT-1 (carnitine palmitoyl transferase-1) expression was not altered. Our results have shown that fenofibrate treatment decreases the hepatic lipid content induced by OA which is mediated by an important increase in fatty acid oxidation consequent to an increase in hepatic mRNA expression of PPARalpha and ACO.
Ferreira
Adaliene Versiani Matos
AV
Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, Belo Horizonte, MG 31270-901, Brazil.
Parreira
Gleydes Gambogi
GG
Porto
Laura Cristina Jardim
LC
Mario
Erica Guihen
EG
Delpuerto
Helen Lima
HL
Martins
Almir Sousa
AS
Botion
Leida Maria
LM
D042962:Acyl-CoA Oxidase / Q000096:biosynthesis; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002469:Cell Separation; D004032:Diet; D011345:Fenofibrate / Q000627:therapeutic use*; D048550:Hepatic Insufficiency / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D050356:Lipid Metabolism / Q000187:drug effects; D008055:Lipids / Q000096:biosynthesis; D008066:Lipolysis / Q000187:drug effects; D008071:Lipoprotein Lipase / Q000378:metabolism; D008099:Liver / Q000473:pathology; D008297:Male; D009963:Orotic Acid / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D047493:PPAR alpha / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000318:Adrenergic beta-Agonists; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D007328:Insulin; D008055:Lipids; D047493:PPAR alpha; D009963:Orotic Acid; D042962:Acyl-CoA Oxidase; D008071:Lipoprotein Lipase; D007545:Isoproterenol; D011345:Fenofibrate