The effects of clofibrate feeding on the metabolism of palmitate and erucate in isolated hepatocytes

Abstract

The metabolism of palmitate and erucate has been investigated in hepatocytes isolated from control rats and from rats fed 0.3% clofibrate. Clofibrate increased the oxidation of [1-14C]palmitate 1.5 to 2-fold while the esterification was decreased. At a high concentration of palmitate (1.5 mM), the total rate of fatty acid metabolism was stimulated. Clofibrate stimulated both the oxidation (3.5 to 5-fold) and the esterfication (1.7-fold) of [14-14C]erucate. Erucate undergoes chain-shortening in isolated liver cells. This chain-shortening was stimulated at least 2-fold by clofibrate feedings. The isolated mitochondrial fraction from clofibrate-fed rats showed an increased capacity for oxidation of short-chain acylcarnitines (including acetylcarnitine), while the oxidation of palmitoyl- and erucoylcarnitine showed little change. It is suggested that erucate is shortened by the recently detected beta-oxidation system of peroxisomes.

Effect of marine oil and rapessee oil on composition of fatty acids in lipoprotein triacylglycerols from rat blood plasma and liver perfusate

“…Ong et al (27) used radioactively labelled erucic acid and showed that the liver took the most active part in the chain shortening of erucic acid, which was mainly converted to oleic acid. Recently, it has been demonstrated that isolated liver cells can metabolize erucic acid in a chain shortening process (28)(29)(30), especially after clofibrate feeding of the rats, a procedure which appeared to stimulate extramitochondrial conversion of erucic acid to shorter monoenic fatty acids (28,29).…”

Clofibrate Increases Long-Chain Fatty Acid Oxidation by Neonatal Pigs

“…The synthesized TGs were purified by alkaline/ ethanolic extraction, and purity ($95%) was confirmed chromatographically using an HPLC system (Waters) equipped with a photodiode array detector (19). The synthesis of [1-14 C]oleic acid and erucic acid TGs followed the same procedure as described above using [1][2][3][4][5][6][7][8][9][10][11][12][13][14] (21). The schedule and duration of the expired CO 2 collection was patterned following the study by Heo et al (20), and the pigs were killed by American Veterinary Medical Association-approved electrocution when the experiment ended, after 24 h of collection.…”

“…Administration of clofibrate increases cellular FA uptake, transport, and oxidation in rodent species specifically for the very-long-chain FAs (VLCFAs) that are oxidized initially in peroxisomes. For instance, the oxidation of erucic acid (22:1n-9) is increased 5-fold in hepatocytes isolated from rats fed clofibrate (9). The effects of clofibrate on gene expression and enzyme activities were well documented in the review by Bremer (10).…”

Regulation of peroxisomal fatty acid oxidation

“…Is it likely that this mechanism could operate in vivo? If it does operate in the intact hepatocyte it could explain the differences described regarding clofibrate-poten-tiated oxidation of palmitate and erucate by isolated hepatocytes [9]. Also the range of CoA concentrations which are effective in vitro are not dramatically different from estimates of the cytosolic CoA concentration (-0.1 mM [lo]).…”

“…This contrasts the marked increase in oxidation of erucic acid observed with hepatocytes isolated from clofibrate-treated animals. Although the hepatocyte oxidation of pahnitate is doubled on clofibrate treatment, a 5-fold increase in oxidation of erucic acid was observed [9]. It is therefore possible that there is a mechanism by which the type of fatty acids which are subjected to peroxisomal &oxidation is regulated.…”