Conversion Of Essential Fatty Acids Research Articles

Utility of the Specialized Pro-Resolving Mediators as Diagnostic and Prognostic Biomarkers in Disease.

A precision medicine approach is widely acknowledged to yield more effective therapeutic strategies in the treatment of patients with chronic inflammatory conditions than the prescriptive paradigm currently utilized in the management and treatment of these patients. This is because such an approach will take into consideration relevant factors including the likelihood that a patient will respond to given therapeutics based on their disease phenotype. Unfortunately, the application of this precision medicine paradigm in the daily treatment of patients has been greatly hampered by the lack of robust biomarkers, in particular biomarkers for determining early treatment responsiveness. Lipid mediators are central in the regulation of host immune responses during both the initiation and resolution of inflammation. Amongst lipid mediators, the specialized pro-resolving mediators (SPM) govern immune cells to promote the resolution of inflammation. These autacoids are produced via the stereoselective conversion of essential fatty acids to yield molecules that are dynamically regulated during inflammation and exert potent immunoregulatory activities. Furthermore, there is an increasing appreciation for the role that these mediators play in conveying the biological actions of several anti-inflammatory therapeutics, including statins and aspirin. Identification and quantitation of these mediators has traditionally been achieved using hyphenated mass spectrometric techniques, primarily liquid-chromatography tandem mass spectrometry. Recent advances in the field of chromatography and mass spectrometry have increased both the robustness and the sensitivity of this approach and its potential deployment for routine clinical diagnostics. In the present review, we explore the evidence supporting a role for specific SPM as potential biomarkers for patient stratification in distinct disease settings together with methodologies employed in the identification and quantitation of these autacoids.

Long-chain polyunsaturated fatty acids in a diabetic teenager during and after nine repeated episodes of diabetic ketoacidosis

Type 1 diabetes is often accompanied with acute hypoinsulinemia that may theoretically inhibit the conversion of essential fatty acids to their longer-chain metabolites. Previously, we found significant reduction in plasma arachidonic (C20:4n-6) and docosahexaenoic (C22:6n-3) acid values in a group of diabetic children during diabetic ketoacidosis. Here we report data on the changes of fatty acids in plasma phospholipids in a diabetic teenager during and after nine subsequent episodes of diabetic ketoacidosis (DKA). Plasma phospholipid linoleic acid (C18:2n-6) values significantly decreased [23.05 (1.05) versus 19.22 (3.22), % w/w, median (IQR), p < 0.01], while values of dihomo-gamma-linolenic acid (C20:3n-6) and docosatetraenoic acid (C22:4n-6) significantly increased [1.72 (0.44) versus 1.80 (0.63) and 0.40 (0.01) versus 0.45 (0.07), respectively, p < 0.05]. Values of alpha-linolenic acid (C18:3n-3) did not change, while values of docosahexaenoic acid were significantly higher after than during the ketoacidosis [1.57 (0.67) versus 1.87 (0.32), p < 0.05). These data obtained in the same patient during repeated episodes of diabetic ketoacidosis support the concept that hypoinsulinemia plays an important role in disturbances of essential fatty acid metabolism in diabetes.

Long-term effects of trans fatty acid intake during pregnancy and lactation: does it have deleterious consequences?

Evaluation of: Pisani LP, Oller do Nascimento CM, Bueno AA et al.: Hydrogenated fat diet intake during pregnancy and lactation modifies the PAI-1 gene expression in white adipose tissue of offspring in adult life. Lipids Health Dis. 7, 13 (2008). Placental transfer of lipid moieties is relatively low compared with other nutrients, but alterations of lipid components at the maternal site during pregnancy and/or lactation may have negative long-term consequences in the offspring. Industrial hydrogenation of edible oils produces trans fatty acids (TFAs). TFAs enhance inflammatory markers and insulin resistance, cross the placenta and interfere in the conversion of essential fatty acids into their long-chain derivatives, which are critical in perinatal development. Pisani et al. have described that adult offspring of rats fed a TFA-rich diet during pregnancy and lactation, and exposed to the same diet after weaning, have increased serum insulin and adiponectin, body fat and adipose tissue PAI-1 mRNA. The expe...

Low contribution of n-3 polyunsaturated fatty acids to plasma and erythrocyte membrane lipids in diabetic young adults

Hypoinsulinemia characteristic to type 1 diabetes may theoretically inhibit the conversion of essential fatty acids to their longer-chain metabolites. Fatty acids were determined in plasma and erythrocyte membrane lipids in young diabetic adults ( n=34) and in age-matched healthy controls ( n=36). Values of linoleic acid (56.01 [5.02] versus 51.05 [7.32], % by wt, median [range from the first to the third quartile], P<0.00l) and arachidonic acid (AA) (11.17 [2.98] versus 9.69 [1.95] P<0.001) were significantly higher in diabetic subjects than in controls. However, α-linolenic acid values did not differ, and docosahexaenoic acid (0.43 [0.12] versus 0.57 [0.29], P<0.01) values were significantly lower in diabetic than in control subjects. Significant inverse correlations were found between AA and hemoglobin A 1c values in the phospholipid ( r=−0.40, P<0.05) and sterol ester ( r=−0.40, P<0.05) fractions. The data obtained in the present study suggest that the availability of n-3 long-chain polyunsaturated fatty acid may be reduced in young diabetic adults.

Expression of Cyclooxygenase Isoforms in Developing Rat Placenta, Human Term Placenta, and BeWo Human Trophoblast Model

Cyclooxygenase (COX) catalyzes the rate-limiting step in the conversion of essential fatty acids (EFAs) to bioactive molecules such as prostaglandins (PGs), which play critical roles in many aspects of female reproduction and in fetal development. There are two primary related COX isoforms, the constitutively expressed COX-1 and the inducible COX-2. Although the expression of COX-1 and COX-2 has been demonstrated in the amnion, chorion, and decidua, relatively little information exists with regard to their expression and physiological function in the placenta during gestation. In this study, we have elucidated the spatial and temporal patterns of COX-1 and COX-2 expression in the labyrinthine and junctional zones of the developing rat placenta, in the human term placenta, and in the BeWo human trophoblast model using semiquantitative RT-PCR, Western blot, and immunohistochemical analyses. The mRNA and protein expression of COX-1 and COX-2 were demonstrated in the developing rat placenta with increasing expression observed toward parturition. COX-2 exhibited greater expression than COX-1 after mid-gestation and had a corresponding shift in spatial expression from the labyrinthine to the junctional zone at term. COX-1 and -2 were also expressed in human term placenta, while BeWo cells exhibited moderate expression of COX-1 and weak expression of COX-2. The results demonstrate that COX-1 and COX-2 are expressed in the rat and human placentas. The differential expression patterns in the rat placenta, especially of COX-2, imply that there may be gestational changes in the biosynthesis of PGs and other potential bioactive EFA metabolites. Establishing the expression of the COX isoforms provides a framework for future investigations into the functional and physiological significance of COX-1 and COX-2 in the placenta, particularly with respect to influencing normal pregnancy and fetal development, and to provide insights into therapeutic utilization of COX inhibitors in pregnancy.

Comparison of Mechanism and Functional Effects of Magnesium and Statin Pharmaceuticals

Since Mg2+-ATP is the controlling factor for the rate-limiting enzyme in the cholesterol biosynthesis sequence that is targeted by the statin pharmaceutical drugs, comparison of the effects of Mg2+ on lipoproteins with those of the statin drugs is warranted. Formation of cholesterol in blood, as well as of cholesterol required in hormone synthesis, and membrane maintenance, is achieved in a series of enzymatic reactions that convert HMG-CoA to cholesterol. The rate-limiting reaction of this pathway is the enzymatic conversion of HMG CoA to mevalonate via HMG CoA. The statins and Mg inhibit that enzyme. Large trials have consistently shown that statins, taken by subjects with high LDL-cholesterol (LDL-C) values, lower its blood levels 35 to 65%. They also reduce the incidence of heart attacks, angina and other nonfatal cardiac events, as well as cardiac, stroke, and total mortality. These effects of statins derive less from their lowering of LDL-C than from their reduction of mevalonate formation which improves endothelial function, inhibits proliferation and migration of vascular smooth muscle cells and macrophages, promotes plaque stabilization and regression, and reduces inflammation, Mg has effects that parallel those of statins. For example, the enzyme that deactivates HMG-CoA Reductase requires Mg, making Mg a Reductase controller rather than inhibitor. Mg is also necessary for the activity of lecithin cholesterol acyl transferase (LCAT), which lowers LDL-C and triglyceride levels and raises HDL-C levels. Desaturase is another Mg-dependent enzyme involved in lipid metabolism which statins do not directly affect. Desaturase catalyzes the first step in conversion of essential fatty acids (omega-3 linoleic acid and omega-6 linolenic acid) into prostaglandins, important in cardiovascular and overall health. Mg at optimal cellular concentration is well accepted as a natural calcium channel blocker. More recent work shows that Mg also acts as a statin.

Conversion of Essential Fatty Acids by Delta 6-Desaturase in Dog Liver Microsomes

Conversion of Essential Fatty Acids by Delta 6-Desaturase in Dog Liver Microsomes

Influences of postnatal age and dietary nucleotides on plasma fatty acids in the weanling rat.

Dietary nucleotides seem to play a number of physiologic roles during early life. They are improved in the maintenance of the immune system, intestinal maturation, and lipid metabolism. Nucleotides affect the conversion of essential fatty acids into their long-chain polyunsaturated (PUFA) derivatives in both preterm and at-term newborn infants. This work examines the effect of postnatal age and dietary nucleotides on the fatty acid composition of total plasma lipids and lipid fractions in the rat. Weanling rats (21 days old) were divided into three groups. The first group was killed, and the other two groups were fed a standard semipurified diet, and the same diet supplemented with 250 mg each of CMP, UMP, AMP, GMP, and IMP per 100 g of diet for 4 weeks. Advancing postnatal age led to an increase of total plasma fatty acids, especially saturated, and PUFA of the n-6 series, whereas PUFA of the n-3 series decreased. The fatty acid profile of plasma phospholipids (PL) exhibited minor changes, although there was a tendency to show lower levels of saturates and PUFA of the n-3 series and increased levels of PUFA of the n-6 series. Cholesteryl esters showed a response similar to that of PL, although the increase in arachidonic acid (20:4n-6) was significant. For triglycerides, linoleic acid (18:2n-6) and monounsaturates increased their levels, whereas saturates decreased. Dietary nucleotides mediated a significant increase in total plasma fatty acids, namely monounsaturated fatty acids and PUFA of both n-6 and n-3 series as compared with the control group. The relative fatty acid composition of PL and cholesteryl esters was mostly unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in fatty acid profiles of red blood cell membranes mediated by dietary nucleotides in weanling rats.

Dietary nucleotides have been described to play multiple physiological roles. We examined the effect of feeding, for 4 weeks, nucleotide-supplemented diets (N-50 and N-250) on red blood cell (RBC) membrane fatty acid composition in weanling rats. Long-chain polyunsaturated fatty acids (LC-PUFA) of the n-6 series, especially arachidonic acid, increased in total RBC phospholipids in N-50 and N-250 groups. Concentrations of LC-PUFA of the n-3 series were preserved or slightly decreased. Saturates and monoenates also decreased. Phosphatidylethanolamine and sphingomyelin followed the variations observed for total phospholipids. Phosphatidylcholine showed a different response; saturated fatty acids increased while n-6 LC-PUFA decreased. Dietary nucleotides seem to affect the conversion of essential fatty acids to their long-chain derivatives in weanling rats in a similar way to that occurring in newborn infants during early life. These results show that the rat may be a valid model with which to study the biochemical mechanisms by which dietary nucleotides affect fatty acid desaturation.

Changes in Fatty Acid Profiles of Red Blood Cell Membranes Mediated by Dietary Nucleotides in Weanling Rats

SummaryDietary nucleotides have been described to play multiple physiological roles. We examined the effect of feeding, for 4 weeks, nucleotide‐supplemented diets (N‐50 and N‐250) on red blood cell (RBC) membrane fatty acid composition in weanling rats. Long‐chain polyunsaturated fatty acids (LC‐PUFA) of the n‐6 series, especially arachidonic acid, increased in total RBC phospholipids in N‐50 and N‐250 groups. Concentrations of LC‐PUFA of the n‐3 series were preserved or slightly decreased. Saturates and monoenates also decreased. Phosphatidyleth‐anolamine and sphingomyelin followed the variations observed for total phospholipids. Phosphatidylcholine showed a different response; saturated fatty acids increased while n‐6 LC‐PUFA decreased. Dietary nucleotides seem to affect the conversion of essential fatty acids to their long‐chain derivatives in weanling rats in a similar way to that occurring in newborn infants during early life. These results show that the rat may be a valid model with which to study the biochemical mechanisms by which dietary nucleotides affect fatty acid desaturation.

Essential fatty acid metabolism in diseases of connective tissue with special reference to scleroderma and to Sjogren's syndrome

Drugs which modify the conversion of essential fatty acids to prostaglandins and leukotrienes are the mainstays of treatment in rheumatology. Yet these drugs have little or no action in scleroderma or Sjogren's syndrome and under some circumstances may have adverse effects. Patients with scleroderma have been shown to have very high levels of circulating prostaglandins, coupled with depletion of the prostaglandin precursors, dihomogammalinolenic acid and arachidonic acid. Levels of the metabolites of arachidonic acid, 22:4n-6 and 22:5n-6, which have major roles in maintaining normal cell membrane characteristics were exceptionally low in both plasma and red cell membranes. Others have observed that various functions are highly resistant to normal actions of PGs in scleroderma. This raises the possibility that the high rate of PG formation in scleroderma may be beneficial, in compensation, and that clinical symptoms develop when PG precursors begin to be depleted. Red cell membrane fatty acids patterns in Sjogren's syndrome are almost identical to those in scleroderma. Placebo-controlled trials of supplementation with essential fatty acids have been found to be beneficial in both scleroderma and Sjogren's syndrome.

The Enzymatic Conversion of Essential Fatty Acids into Prostaglandins: PROSTAGLANDINS AND RELATED FACTORS 34

The Enzymatic Conversion of Essential Fatty Acids into Prostaglandins: PROSTAGLANDINS AND RELATED FACTORS 34