Changes in rat liver chromatin after administration of a mixture of amino acids

It was shown that injections of an amino acid mixture essentially increase the number of nuclease-sensitive regions of chromatin and its active fraction (Mg2+-soluble fraction), while hydrocortisone increases the amount of the latter, which is less sensitive to the effect of DNAase II. Genome activation during nonhormonal induction after administration of the amino acid mixture or during hydrocortisone injection reflects in different ways on the parameters of melting of chromatin active fractions and on the relative content of its protein fractions.     

Changes in unsaturated fatty acids in serum lipids of hamsters infected with schistosomes (S. mansoni)

Measurements have been made of the fatty-acid composition of lipids in normal hamster sera compared with sera of hamsters infected with Schistosoma mansoni. The results show a consistent decrease of linoleic and eicosapentaenoic acids, and an increase in arachidonic acid in the phosphatidylcholine and lysophosphatidylcholine of the infected animals. Arachidonic acid was also increased in cholesterol ester, and docosahexaenoic acid was raised in free fatty acid and in phosphatidylcholine in sera from infected animals.     

Trans unsaturated fatty acids are less oxidizable than cis unsaturated fatty acids and protect endogenous lipids from oxidation in lipoproteins and lipid bilayers

Epidemiological data suggest that dietary trans unsaturated fatty acids increase the risk of heart disease; however, the underlying mechanisms are unclear. In this study, we investigated one possible mechanism, namely, their effect on LDL oxidation. Supplementation of LDL with 10% 16:1 trans-cholesteryl ester (CE) inhibited the oxidation compared to that with 16:1 cis-CE. Total replacement of core lipids with 18:2 trans,trans-CE decreased the rate of LDL oxidation by 19% compared to replacement with 18:2 cis,cis-CE. When the surface phosphoglycerides were replaced with either 16:0-18:2 cis,cis-phosphatidylcholine (PC) or 16:0-18:2 trans,trans-PC, the latter was found to inhibit the rate and increase the lag time of oxidation to a greater extent than the former. To confirm these findings, we studied the oxidation of PC liposomes by assessing the formation of conjugated dienes or the degradation of a fluorescently labeled PC. By both methods, the 16:0-18:2 trans,trans-PC exhibited greater resistance to oxidation than the 16:0-18:2 cis,cis-PC. Eliminating the fluidity differences did not completely eliminate the differences in oxidation rates, suggesting that the trans double bond is inherently resistant to oxidation. The composition of the conjugated hydroperoxy products formed after oxidation differed markedly for the two 18:2 isomers. Supplementation of 16:0-18:2 cis,cis-PC liposomes with 20 mol % di16:1 trans-PC retarded oxidation rates to a greater extent than supplementation with di16:1 cis-PC. These studies show that dietary trans unsaturated fatty acids decrease the rate of lipid peroxidation, an effect that may mitigate the atherogenic effect of these fatty acids.     

Changes in liver microsome lipids and plasma fatty acids induced by dietary orotate in the weanling rat.

1. Dietary orotate produced a decrease in total plasma fatty acids which was reflected in low values of saturated, monounsaturated and polyunsaturated fatty acids longer than 18 carbon atoms of the n-6 series. The relative content of saturated fatty acids in microsomes of animals fed orotate was also decreased. 2. Rat liver delta-9 desaturase activity was lower in the group fed orotate. However, delta-6 desaturase activity did not show significant differences between the groups. 3. Microsomal cholesterol content was lower in rats fed orotate than in controls but phospholipid phosphorus contents were similar. These results suggest a direct effect of dietary orotate on the key enzymes which regulates cholesterol liver metabolism.     

Disruption of mitochondrial beta -oxidation of unsaturated fatty acids in the 3,2-trans-enoyl-CoA isomerase-deficient mouse

Cellular energy metabolism is largely sustained by mitochondrial beta-oxidation of saturated and unsaturated fatty acids. To study the role of unsaturated fatty acids in cellular lipid and energy metabolism we generated a null allelic mouse, deficient in 3,2-trans-enoyl-CoA isomerase (ECI) (eci(-/-) mouse). ECI is the link in mitochondrial beta-oxidation of unsaturated and saturated fatty acids and essential for the complete degradation and for maximal energy yield. Mitochondrial beta-oxidation of unsaturated fatty acids is interrupted in eci(-/-)mice at the level of their respective 3-cis- or 3-trans-enoyl-CoA intermediates. Fasting eci(-/-) mice accumulate unsaturated fatty acyl groups in ester lipids and deposit large amounts of triglycerides in hepatocytes (steatosis). Gene expression studies revealed the induction of peroxisome proliferator-activated receptor activation in eci(-/-) mice together with peroxisomal beta- and microsomal omega-oxidation enzymes. Combined peroxisomal beta- and microsomal omega-oxidation of the 3-enoyl-CoA intermediates leads to a specific pattern of medium chain unsaturated dicarboxylic acids excreted in the urine in high concentration (dicarboxylic aciduria). The urinary dicarboxylate pattern is a reliable diagnostic marker of the ECI genetic defect. The eci(-/-) mouse might be a model of a yet undefined inborn mitochondrial beta-oxidation disorder lacking the enzyme link that channels the intermediates of unsaturated fatty acids into the beta-oxidation spiral of saturated fatty acids.     

Evidence of the oxidation of unsaturated fatty acids in cataracts

Gas chromatography analysis with the use of an electron captured detector including preparation of the halogen-substituted derivatives of fatty acids is a useful tool for the detection of lipid peroxidation products both in vitro and in vivo. This technique was applied to determine the content of fatty acid oxy-derivatives in lipid samples of transparent and completely opaque human lenses. At the stage of mature cataract a significantly increased level of oxyproducts was observed in the lens lipid fraction. It was concluded that accumulation of polar oxygroups in the lipid bilayer of plasma membranes of lens fibres is a plausible cause of their damage in cataracts.