Role of oleic acid in the metabolism of essential fatty acids

Groups of young male guinea pigs were fed diets containing corn oil, coconut oil, coconut oil plus elaidic acid, and coconut oil plus oleic acid. The oleic acid-fed group showed signs of essential fatty acid deficiency after four weeks and severe signs after eight weeks. The elaidic acid-fed group did not show these symptoms. It is proposed that oleic acid competes competitively with linoleic acid as a substrate for the enzymes involved in linoleate transformations when only a very limited supply of linoleic acid is available to the animals and oleic acid is made available in relatively large amounts. A detailed analysis of the serum, liver, and adipose tissue lipid and a study of the incorporation of acetate-1-C¹⁴ into different lipids is presented. This paper is based on work supported in part by United States Public Health Grant No. HTS 5306 and by a grant from the Nutrition Foundation Inc., New York.     

The metabolism of polyenoic fatty acids

Feeding experiments with C¹⁴-labeled and unlabeled unsaturated fatty acids have been used to study the possible routes of formation of the C₂₀- and C₂₂-polyenoic fatty acids of rat liver phosphatides. The acids of the palmitoleate, oleate, linoleate, and linolenate types (considered on the basis of the position of the double bond closest to the methyl end) are apparently formed from the C₁₆ and C₁₈ unsaturated acids of the corresponding types. The results rule out possible transformations of the C₂₀- and C₂₂-polyenoic acids from one type to another, and demonstrate the exclusive introduction of new double bonds toward the carboxyl group. Isomers of linoleate or linolenate in which the double bonds were shifted by one carbon atom toward the carboxyl or methyl groups were incorporated into the phosphatides only to a negligible extent in the form of polyenoic acids.     

Nonessential fatty acids in formula fat blends influence essential fatty acid metabolism and composition in plasma and organ lipid classes in piglets

The n-6 and n-3 fatty acid status of developing organs is the cumulative result of the diet lipid composition and many complex events of lipid metabolism. Little information is available, however, on the potential effects of the saturated fatty acid chain length (8:0–16:0) or oleic acid (18:1) content of the diet on the subsequent metabolism of the essential fatty acids 18:2n-6 and 18:3n-3 and their elongated/desaturated products. The effects of feeding piglets formulas with fat blends containing either coconut oil (12:0±14:0) or medium chain triglycerides (MCT, 8:0±10:0) but similar levels of 18:1, 18:2n-6 and 18:3n-3, or MCT with high or low 18:1 but constant 18:2n-6 and 18:3n-3 on the fatty acid composition of plasma, liver and kidney triglycerides, phospholipids and cholesteryl esters, and of brain total lipid, were studied. Diet-induced changes in the fatty acid composition of lipid classes were generally similar for plasma, liver and kidney. Dietary 18:1 content was reflected in tissue lipids and was inversely associated with levels of 18:2n-6. Lower percentage of 18:2n-6, however, was not associated with lower levels of its elongated/desaturated product 20:4n-6 but was associated with higher levels of 22:6n-3. Feeding coconut oilvs. MCT resulted in lower 18:1 levels in all lipids, and higher percentages of 20:4n-6 in tissue phospholipid. Increasing the dietary n-6/n-3 ratio from 5 to 8 significantly increased tissue percentage of 18:2n-6 and decreased phospholipid 22:6n-3. In contrast to plasma, liver and kidney, brain lipid fatty acid composition was not influenced by the formula saturated fatty acid chain length, content of 18:1, or n-6/n-3 ratio. In summary, the studies show that the dietary requirement for n-6 and n-3 fatty acids may be influenced by the nonessential saturated and monounsaturated fatty acids fed concurrently.     

Nonessential fatty acids in formula fat blends influence essential fatty acid metabolism and composition in plasma and organ lipid classes in piglets

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Rat testicular lipids and dietary isomeric fatty acids in essential fatty acid deficiency

Weanling rats were fed essential fatty acid-deficient diets, either completely fat-free, or with partially hydrogenated fish oil (PHFO, 28 wt %), or with fractions derived from PHFO containing primarily positional isomers oftrans-eicosenoate (20∶1, 3 wt %) ortrans-docosenoate (22∶1, 3 wt %). Control animals were fed a peanut oil-containing diet (28 wt %). After 5 or 15 weeks on the diet, the content of neutral and phosphorus-containing lipids in the testes was determined. The fatty acid distribution in major lipid classes was analyzed for animals fed the diets for 15 weeks. The testicular stage of maturation or degeneration was assessed by histology. The group fed PHFO exhibited signs of complete testicular degeneration, or lack of maturation, already after 5 weeks, whereas the animals on the diets with the very long chain monoenoic acids suffered severe degenerations only after 15 weeks. In the PHFO-fed rats, a sharp decline in the concentration of testicular triacylglycerols was observed. In all of the essential fatty acid-deficient groups, an increase in testicular sphingomyelin was observed. Cholesterol levels were fairly similar among all dietary groups. The total testicular fatty acids of the PHFO-fed animals contained somewhat more eicosadienoic acid than found in the other groups, and somewhat less (n−9)-acids. In all EFA-deficient groups, (n−6)-acids were lowered, in particular in triacylglycerols and phosphatidyl cholines. The PHFO group did not show a lower (n−6)-concentration than the other deficient groups, in spite of the more severe symptoms of deficiency. There was no evidence of a major accumulation of long chain isomeric fatty acids in the degenerated testes of the PHFO-, 20∶1, and 22∶1-fed groups.     

Role of essential fatty acids in the function of the developing nervous system

The basis for n-3 fatty acid essentiality in humans includes not only biochemical evidence but functional measures associated with n-3 deficiency in human and nonhuman primates. Functional development of the retina and the occipital cortex are affected by α-linolenic acid deficiency and by a lack of docosahexaenoic acid (DHA) in preterm infant formulas and, as reported more recently, in term diets. Functional effects of n-3 supply on sleep-wake cycles and heart rate rhythms support the need for dietary n-3 fatty acids during early development. Our results indicate that n-3 long-chain polyunsaturated fatty acids should be considered provisionally essential for infant nutrition. DHA may also be required by individuals with inherited metabolic defects in elongation and desaturation activity, such as patients with peroxisomal disorders and some forms of retinitis pigmentosa.     

The chemical and biological assay of essential fatty acids

After defining and developing the background of essential fatty acids, the various chemical, biological and physical methods which have been used for their assay will be reviewed. Specific recommendations will be made regarding techniques in each method category for natural and processed fats. Special attention will be given to the distinction between the essential fatty acids and the other polynnsaturated acids. Outlined analysis of paper soon to appear in Vol. I of a series, “Analysis and Characterization of Oils, Fats and Fat Products,” H. Boekenoogen, editor, John Wiley & Sons, Ltd., London.     

Studies on the metabolism of linoelaidic acid in the essential fatty acid-deficient rat

Male weanling rats of the Sprague-Dawley strain were made essential fatty acid (EFA)-deficient by feeding them a fat-free diet for five months. The animals were then fed a supple-ment of methyltrans-9,trans-12-octadecadienoate (methyl linoelaidate), as 5% of the dietary calo-ries (approximately 400 mg/animal/day) for 19 days, and killed by exsanguination. The com-position of the liver, kidney, epididymal and plasma lipids was determined and compared with that obtained from EPA-deficient rats given oral supplements of methylcis-9,cis-12-octadeca-dienoate (linoleate) and methylcis-9,trans-12- octadecadienoate. Linoelaidic acid was depos-ited in the phospholipids, sterol esters and tri-glycerides in all of the tissues examined. Iso-lation analysis of the fatty acids showed no evidence that linoelaidic acid was converted to higher polyunsaturated fatty acids in the EFA-deficient rat. Supported in part by U. S. Public Health Service Grant No. AM 04942.     

Dietary intake of essential and long-chain polyunsaturated fatty acids in pregnancy

The dietary intake of EFA and long-chain PUFA (LCPUFA) by women with (n=14) and without (n=31) gestational diabetes mellitus (GDM) was determined by repeated 24-h recalls. Women with GDM consumed significantly more energy as fat compared with women who had uncomplicated pregnancies; absolute dietary fat did not differ. Dietary n−3 LCPUFA was substantially lower than the current recommendation for pregnancy, whereas intake of saturated FA (SFA) exceeded it. We conclude that replacing dietary sources of SFA with those of EFA and LCPUFA, especially n−3 LCPUFA, would benefit the dietary fat profiles of all pregnant women.     

必需脂肪酸在美容化妆品中的应用

必需脂肪酸（EFAs）可以使皮肤增益，加强细胞膜结构与功能，维持并恢复皮肤天然屏障，预防皮肤刺激和炎症，以及增强细胞膜的通透性。详述了必需脂肪酸的新陈代谢过程和其在美容化妆品中的应用。     

Intestinal metabolism of plasma free fatty acids in streptozotocin diabetic rats

Moderate insulin deficiency was reported to be accompanied by an increased production of intestinal very low density lipoprotein (VLDL) triglyceride in the rat. Because plasma free fatty acids (FFA) are incorporated into triglyceride by intestinal mucosa of rats and humans and plasma FFA are increased in insulin-deficient diabetes mellitus, we investigated several aspects of the intestinal metabolism of plasma FFA in diabetic rats. All experiments were performed on the third day following the i.v. injection of streptozotocin (45 mg/kg body weight) or buffer alone. A (¹⁴C)palmitic acid-rat serum complex was rapidly injected intravenously and its initial uptake by small bowel mucosa, the intracellular incorporation into lipids and water soluble metabolites and the specific radioactivity of triglycerides of mucosal homogenates was determined. No significant differences could be found between diabetic and control rats at 2 and 5 min after¹⁴C-palmitate i.v., suggesting that neither the influx of plasma free fatty acids into intestinal mucosal cells nor their initial intracellular metabolic pathways are significantly altered in moderately diabetic rats. A pronounced decrease in intestinal mucosal triglyceride at 10 min after¹⁴C-palmitate i.v. might be interpreted as indirect evidence for an enhanced triglyceride efflux from intestinal mucosa into mesenteric lymph in diabetic rats.     

Abnormal metabolism of polyunsaturated fatty acids and phospholipids in diabetic glomeruli

Studies were done on changes in phospholipid content and fatty acid composition of phospholipids and on the role of the acylation pathway in synthesis of phospholipids in the development of abnormal fatty acid composition in the glomeruli of rats 2 and 10 mo after induction of diabetes with streptozotocin. The proportions of individual phospholipids in the glomeruli of rats were not changed 2 mo after induction of diabetes, but the proportion of phosphatidylethanolamine (PE) decreased and that of sphingomyelin increased 10 mo after induction of diabetes. In contrast, in liver the proportion of PE was increased and that of phosphatidylcholine was decreased. These results showed that changes of individual phospholipids in glomeruli were time-dependent and tissue-specific. Two mo after induction of diabetes, the main change in the phospholipid fatty acid composition of diabetic glomeruli was a decrease in arachidonic acid (AA); the main change in serum free fatty acids (FFA) was an increase in linoleic acid (LA) and a decrease in AA. Ten mo after induction of diabetes, the main changes in the phospholipid fatty acid composition of glomeruli were an increase in LA and a decrease in AA; the main change of the serum FFA composition was a decrease in AA. Thus, the fatty acid composition of glomerular phospholipids was not directly correlated to that of the serum in diabetic rats. Acyl-CoA synthetase and acyltransferase activities increased in diabetic glomeruli with either AA or LA as substrate, but activity toward LA increased more at 2 mo after induction of diabetes. Acyl-CoA synthetase activity increased in diabetic glomeruli with LA as substrate, but that did not change with AA as substrate at 10 mo after induction of diabetes. Furthermore, acyltransferase activity decreased in diabetic glomeruli with AA as substrate, although that did not change with LA as substrate at 10 mo after induction of diabetes.     

Effect of chronic ingestion of DDT on physiological and biochemical aspects of essential fatty acid deficiency

Male weanling rats were fed semipurified diets with and without essential fatty acid (EFA) and DDT (150 ppm) for 14 weeks to determine the effects of the pesticide on physiological and biochemical aspects of EFA deficiency (EFAD). DDT did not affect EFAD-induced reduction in growth rate or final body weight, nor did the pesticide affect EFAD-induced changes in feed efficiency or skin dermatitis. The pesticide did increase liver/body mass ratios, but did not interact with EFAD, which also increased this ratio. The pesticide produced complex changes in total fatty acid composition of liver and tail skin: liver levels of 18∶0, 18∶2 and 20∶3ω9 were increased, whereas levels of 12∶0, 14∶0 and 16∶0 were decreased. In both tissues, DDT interacted with EFA to increase 18∶2 levels. DDT did not change the total fatty acid 20∶3ω9/20∶4ω6 ratio in either tissue. In this study, although DDT did not exacerbate the physiological aspects of EFAD, DDT-induced changes in fatty acid composition of liver and tail skin indicated that 150 ppm DDT in the diets did alter lipid metabolism of the rats in an unexplained manner. Scientific contribution No. 811, Storrs Agricultural Experimental Station, University of Connecticut, Storrs, CT 06268.     

Cholesterol-cerebroside interaction: The role of α-hydroxy fatty acids

The esterification of cholesterol by the plasma phosphatidyl choline-cholesterol acyltransferase reaction was studied by two methods, radioisotopic and colorimetric, in the presence of cerebroside, ceramide, or methyl esters of lignoceric or α-hydroxy lignoceric acid. The radioisotopic method measures esterification of exogenous labeled cholesterol which must be taken up into the lipoprotein-bound pool prior to its utilization as a substrate. The colorimetric method measures esterification of endogenous lipoprotein-bound free cholesterol since the exogenous labeled cholesterol is negligible in concentration. Cerebroside and ceramide containing α-hydroxy fatty acids reduced the utilization of exogenous labeled cholesterol as substrate, but had no effect on lipoprotein-bound exogenous cholesterol esterification. Cerebroside and ceramide containing no α-hydroxy fatty acid had no effect on exogenous labeled cholesterol esterification. The methyl esters of lignoceric acid and α-hydroxy lignoceric acid had no effect on the esterification of exogenous cholesterol in plasma. There is a decrease in esterification of exogenous labeled cholesterol with increasing concentration of α-hydroxy fatty acid ceramide. Increasing the concentration of exogenous cholesterol tends to counteract the effect of the ceramide on cholesterol esterification. There was little effect on exogenous cholesterol esterification when the α-hydroxy fatty acid ceramide was exposed to plasma before adding the labeled cholesterol. The findings demonstrate an interaction between free cholesterol and cerebroside or ceramide containing α-hydroxy fatty acids, but the nature of the interaction is not elucidated.     

Uptake and metabolism of fatty acids by Soybean suspension cells

Soybean suspension cultures very rapidly take up C₁₆ and C₁₈ fatty acids by a nonspecific, nonenzymic binding of exogeneously added fatty acids to cell walls and by a subsequent transfer into the cell where they are rapidly incorporated into triacylglycerols, phosphatidylcholines, and phosphatidylethanolamines.¹⁴C-Palmitic and¹⁴C-stearic acids follow this sequence but are not desaturated, wherease¹⁴C-oleic and¹⁴C-linoleic acids are transferred more rapidly than the saturated fatty acids and are then further modified. All the data fit a sequence of events by which free oleic acid is first activated to a CoA thioester, and then desaturated to linoleyl-CoA; both thioesters are then transferred to triacylglycerols, phosphatidylcholine, and phosphatidylethanolamine.     

Comparison of various analytical techniques for the determination of essential fatty acids in hardened fats

In partially hydrogenated fats containing residual linoleic acid, linoleic acid isomers are found which have no essential fatty acid activity but contribute to the C-18 diene acid values; i.e., to the so-called linoleic acid values obtained by the usual physicochemical methods. Such hydrogenated fats and oil blends, particularly margarine oils, have now been analyzed by a biochemical procedure in the attempt to measure specifically the essential fatty acid content by a direct method. The latter procedure makes use of a lipoxidase enzyme specific for thecis, cis, methylene interrupted diene structure in polyunsaturated fatty acids having two or more double bonds. It is concluded that the biochemical method is equally as reliable as the combined use of the spectrophotometric and thiocyanometric procedures for estimating with precision the essential fatty acid content of hydrogenated fats containing residual dienes; the simplicity and speed of the biochemical method make it the procedure of choice.