[Dyslipidemic patients with coronary cardiopathy. Effect of different doses of OMEGA-3 fatty acids on serum lipids and lipoproteins]. / Dislipidemicos con cardiopatia coronaria. Efecto de diferentes dosis de acidos grasos omega 3 sobre los lipidos y lipoproteinas sericas.

Twenty one male patients aged 35 to 70 years, with coronary artery disease and dislipidemia refractory to dietary treatment, were assigned to three parallel groups of 7 individuals each that received a supplemental dose of 2, 4 and 6 g/day of omega-3 fatty acids during 60 days. After a 30 days wash-out period and 60 of supplementation, subjects were weighed, a dietary survey was performed, serum levels of total cholesterol and triglycerides, the lipid content of serum lipoproteins and the content of EPA+DHA in plasma phospholipids were measured. A dose dependent increase in EPA+DHA content of phospholipids and no changes in weight or nutrient intake were observed during the supplementation period. With the 6 g dose, a significant reduction in total cholesterol, with a reduction in VLDL and increase in LDL cholesterol and a decline in VLDL triglycerides was observed. With the 4 g dose a reduction in total cholesterol at the expense of VLDL and HDL cholesterol and a reduction in VLDL triglycerides but no changes in total triglycerides was observed. No changes in serum lipids were observed with 2 g dose. In patients with type IIA hyperlipidemia, a significant positive correlation was observed between DHA+EPA content of plasma phospholipids and LDL cholesterol, this correlation was not observed in patients with IIB or IV phenotypes. It is concluded that omega-3 fatty acids are ineffective as the only treatment for dislipidemias refractory to diet.

Peroxisomal fatty acid oxidation and inhibitors of the mitochondrial carnitine palmitoyltransferase I in isolated rat hepatocytes.

Fatty acid oxidation was studied in the presence of inhibitors of carnitine palmitoyltransferase I (CPT I), in normal and in peroxisome-proliferated rat hepatocytes. The oxidation decreased in mitochondria, as expected, but in peroxisomes it increased. These two effects were seen, in variable proportions, with (+)-decanoylcarnitine, 2-tetradecylglycidic acid (TDGA) and etomoxir. The decrease in mitochondrial oxidation (ketogenesis) affected saturated fatty acids with 12 or more carbon atoms, whereas the increase in peroxisomal oxidation (H2O2 production) affected saturated fatty acids with 8 or more carbon atoms. The peroxisomal increase was sensitive to chlorpromazine, a peroxisomal inhibitor. To study possible mechanisms, palmitoyl-, octanoyl- and acetyl-carnitine acyltransferase activities were measured, in homogenates and in subcellular fractions from control and TDGA-treated cells. The palmitoylcarnitine acyltransferase was inhibited, as expected, but the octanoyltransferase activity also decreased. The CoA derivative of TDGA was synthesized and tentatively identified as being responsible for inhibition of the octanoylcarnitine acyltransferase. These results show that inhibitors of the mitochondrial CPT I may also inhibit the peroxisomal octanoyl transferase; they also support the hypothesis that the octanoyltransferase has the capacity to control or regulate peroxisomal fatty acid oxidation.

Protein phosphorylation in peroxisomes.

The possible presence of phosphorylated proteins in peroxisomes was studied in hepatocytes from nafenopin-treated and normal rats. A 63 kDa phosphorylated protein was consistently and exclusively found in the membrane of peroxisomes from hepatocytes incubated in the presence of 32P-phosphate. The peroxisomes were isolated in metrizamide isopycnic gradients of postnuclear supernatants and were subfractionated by alkaline extraction to separate the membrane and the matrix proteins. Polyacrylamide gel electrophoresis, autoradiography and densitometry were employed to characterize the proteins. The 63 kDa membrane protein copurifies with peroxisomes in metrizamide gradients and apparently can be phosphorylated, in purified peroxisomes, with ATP and catalytic subunit of cAMP-dependent protein kinase.