Hypolipidaemic effects of fenofibrate and fasting in the herbivorous grass carp (Ctenopharyngodon idella) fed a high-fat diet

Abstract

We investigated whether the hypolipidaemic effect of fenofibrate and fasting observed in most omnivorous mammals may also apply to herbivorous fish. Grass carp (Ctenopharyngodon idella) fed a high-fat (8 %) diet exhibited a marked increase in blood lipids and body fat after 6 weeks. They were then treated with fenofibrate (100 mg/kg body weight) in the same high-fat diet for 2 weeks, followed by fasting for 1 week. Plasma lipid concentration, body fat amount, fatty acid composition, plasma thiobarbituric acid-reactive substances and some parameters related to hepatic fatty acid oxidation were measured, and liver samples were stained for histological examination. Fenofibrate treatment decreased TAG and cholesterol concentrations in plasma, total lipids of the whole body and liver, and EPA and DHA contents in tissues. Further, a mobilisation of mesenteric fat concomitant with an increase in hepatic peroxisomal fatty acid oxidation and lipid peroxidation was observed. Compared with fenofibrate treatment, fasting decreased body weight and plasma TAG, but not plasma cholesterol. It also reduced the fat content of the whole body and increased the EPA and DHA contents in the liver and other tissues. Fatty acid oxidation was stimulated by fasting in mitochondria, but not in peroxisomes. These data suggest that fenofibrate and fasting regulate the lipid metabolism in grass carp through different metabolic pathways. The grass carp is moderately responsive to a fibrate derivative in comparison with the well-known excess responsiveness of the rat model, and so it could be used for the study of lipid abnormalities as a herbivorous model. Fibrate derivatives are widely used as normolipidaemic or hypolipidaemic drugs for the treatment of hypertriacylglycerolaemic and/or hypercholesterolaemic patients (1 -3) . As a lipid-lowering agent, fenofibrate has been shown to lower the concentration of plasma TAG and cholesterol (4,5) . Some mechanisms of clinical effects of fenofibrate have been identified, including interference with fatty acid (FA) synthesis, stimulation of hepatic FA oxidation, increase in lipoprotein lipolysis, inhibition of cholesterol biosynthesis, induction of hepatic uptake of cholesterol from plasma and increased elimination of cholesterol into bile as biliary acids (6) . Fenofibrate is also known to activate the transcriptional factor PPARa, which binds to the peroxisome proliferator response element in the regulatory region of target genes (7,8) . By this way, PPARa is known to induce enzymes involved in the regulation of lipid metabolism, particularly those related to mitochondrial and peroxisomal FA oxidation (9 -12) . It has also been suggested that fenofibrate regulates body weight (BW) and energy homeostasis by increasing FA oxidation (13) .Similarly to fibrate derivatives, fasting also activates PPARa and thereby regulates mitochondrial and peroxisomal FA oxidation activities (14,15) . The regulation of these pathways affects the lipid metabolism and was effectively demonstrated to modulate blood lipi...

Effects of the PPARα agonist WY-14,643 on plasma lipids, enzymatic activities and mRNA expression of lipid metabolism genes in a marine flatfish, Scophthalmus maximus

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Chronic effects of clofibric acid in zebrafish (Danio rerio): A multigenerational study

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