Effect of dietary nucleotides on the fatty acid composition of rat liver microsomes
The present study was designed to evaluate the influence of dietary nucleotides on the lipid composition of liver microsomes in weanling rats. Rats at weaning were fed, one group with a semipurified nucleotide-free diet and three groups with the same diet supplemented with three different levels of each of the nucleotides AMP, GMP, IMP, UMP and CMP, during 4 weeks. Long chain polyunsaturated fatty acids of the n-6 and n-3 series were increased in phospholipids of liver microsomes for rats fed the nucleotide supplemented diets; however, the cholesterol/phospholipid phosphorus ratio was maintained fairly constant. The results obtained suggest that dietary nucleotides modify the polyunsaturated fatty acid metabolism through a lower rat liver delta-9 desaturase activity and through increased activities of delta-5 and delta-4 desaturases.
Available from: Luis Fontana
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ABSTRACT: Dietary nucleotides modulate a number of metabolic processes, including long-chain polyunsaturated fatty acid metabolism. In this study, we evaluated the effect of dietary nucleotides on plasma and liver microsomal fatty acid profiles in a rat model of liver cirrhosis induced by oral intake of thioacetamide.
Fifty-four female Wistar rats were assigned to one of the following groups: rats in the thioacetamide group (n=45) were given 300 mg thioacetamide/l in their drinking water for 4 months, and rats in the control group (n=9) received water during the same period. After 4 months of treatment, 9 rats in each group were killed. The remaining rats in the thioacetamide group were divided into two new groups, and the animals in each were allowed to recover for 1 or 2 weeks on either a nucleotide-free diet or the same diet supplemented with 50 mg of each of the following: AMP, GMP, CMP, IMP and UMP per 100 g diet.
Saturated (mainly stearic acid), monounsaturated, and n-6 long-chain polyunsaturated fatty acids (mainly arachidonic acid), and also the unsaturation index decreased in plasma of rats with experimental cirrhosis. Administration of the diet supplemented with nucleotides to thioacetamide-treated rats corrected plasma levels of saturated, n-6 long-chain polyunsaturated fatty acids and the unsaturation index. In liver microsomes, the cirrhotic rats showed lower levels of protein and higher levels of palmitic, oleic, linoleic and arachidonic acids. Protein concentrations and levels of all the above-mentioned fatty acids were corrected with the nucleotide-enriched diet.
Dietary nucleotides contribute to correcting plasma and liver microsomal fatty acid alterations in rats with liver cirrhosis induced by chronic oral administration of thioacetamide.
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ABSTRACT: Nucleotides are low molecular weight biological compounds that play major roles in almost all-biological processes. Cell nucleic acids and nucleotides are continuously synthesised, degraded and salvaged. The body’s pools derive from three potential sources: synthesis de novo, salvage (recycling of preformed bases) and the diet. It is generally accepted that de novo synthesis of both purines and pyrimidines from amino acid precursors is capable of supporting the cellular needs for nucleic acid synthesis. When protein intake is decreased or in situations in which there are a high demand of nucleotides synthesis (after gut injury, after surgical trauma, sepsis, rapid growth: pregnancy or newborn infants, etc.) some tissues with a rapid turnover (gut and immune system) may increase the salvage of exogenous nucleotides coming from the diet. Therefore, nucleotides may become conditionally essential nutrients. This article discusses the possible beneficial effects of dietary nucleotides on small intestine (maturation and recovery) and gut microflora, lipid and hepatic metabolism and on the immune system. Human milk is the best source of nucleotides for young infants and the nucleotide/nucleoside profile of it shows a substantial predominance for pyrimidines as compared to purines. Moreover, pyrimidine nucleotides seem to be better preserved in breast milk during storage in the breast and during digestion in the small intestine and they are more absorbed and incorporated into tissue RNA, as compared to purine ones. Additional research should be done to improve the design of nucleotides supplemented infant formulas. This includes: 1) to investigate in vivo if the incorporation of dietary nucleotides in tissue RNA is enhanced in situations of stress or rapid growth and 2) to study the biological effects of individually administered purine and pyrimidine nucleotides.
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ABSTRACT: The deficiency of polyunsaturated fatty acids (PUFA) that occurs in plasma of patients with liver cirrhosis has been assessed in rats with severe steatosis and mild liver necrosis induced by repeated administration of low doses of carbon tetrachloride (CCl(4)). The contribution of both dietary (n-3) long-chain PUFA and nucleotides to the recovery of the altered fatty acid profiles of tissue lipids of these rats has also been studied. Two groups of rats were used. The first was intraperitoneally injected 0.15 ml of a 10% (v/v) CCl(4)solution in paraffin per 100 g of body weight, three times a week for 9 weeks; the second received paraffin alone. After the treatment, six rats of each group were killed. Afterwards, the remaining controls were fed a semipurified diet (SPD) for 3 weeks, and the remaining rats in the CCl(4)group were divided into three new groups: the first was fed the SP diet; the second was fed the SP diet supplemented with 1% (n-3) polyunsaturated fatty acids (PUFA diet); and the third was fed the SP diet supplemented with 250 mg nucleotides per 100 g diet (NT diet). Fatty acids of plasma, erythrocyte membranes and liver microsomes were analyzed. Decreases in linoleic and arachidonic acids in both total plasma lipids and liver microsomal phospholipids were the main findings due to CCl(4)treatment. The rats that received CCl(4)and the PUFA diet showed the lowest levels of (n-6) PUFA and the highest levels of (n-3) PUFA in liver microsomal phospholipids, as well as a significant increase of (n-3) PUFAs in total plasma lipids. The animals that received the NT diet showed no signs of fatty infiltration and exhibited the highest levels of (n-6) PUFAs in liver microsomal phospholipids. These results show that CCl(4)affects fatty acid metabolism which is accordingly reflected in altered tissue fatty acid profiles, and that balanced diets containing PUFA and nucleotides are important for the recovery of the damaged liver in rats.
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