Alpha-linolenic acid, long-chain n-3 fatty acids, and neonatal brain development.

There appear to be mechanisms that enable the developing brain to regulate its concentration of 22:6n-3 in response to both dietary deficiencies and excesses. This appears to be true whether the n-3 fatty acids are supplied as 18:3n-3 or the long-chain derivatives, suggesting that the presence of 22:6n-3 during development may be of functional consequence to the operation of the nervous system. Although there is experimental support for specific effects of n-3 fatty acids on retinal function, further studies with better methodological controls are needed before effects on cognitive function in rodents can be considered unequivocal.     

Dietary fatty acids temporarily alter liver very long-chain fatty acid composition in mice.

To determine the influence of dietary fatty acids on tissue very long-chain fatty acid (VLFA) composition, mice were fed four diets containing 15 g fat/100 g diet derived largely from either safflower oil, peanut oil, olive oil or glycerol trioleate oil. The diets varied widely in the composition of VLFA and other fatty acids. Digestibility of total dietary VLFA ranged from 84.6% in mice fed the glycerol trioleate diet to 96.7% in those fed the safflower oil diet. After 3 mo, the saturated VLFA composition of liver total lipids and sphingomyelin was lower in animals fed the glycerol trioleate oil diet than in mice fed most other diets. Although the saturated VLFA content of the peanut oil diet was more than 15-fold greater than that of the other diets, animals fed the peanut oil diet showed little or no selective increase in liver saturated VLFA. The VLFA composition of brain was comparable in all dietary groups. After 8 mo of feeding, the liver saturated VLFA composition tended to increase and differences between groups disappeared. Liver peroxisomal beta-oxidation of lignocerate (24:0) was similar among all dietary groups. These results demonstrate that dietary fatty acids shorter than VLFA temporarily influence the saturated VLFA composition of liver.     

Dietary fatty acids and cholesterol differentially modulate HDL cholesterol metabolism in Golden-Syrian hamsters

Dietary fatty acids alter HDL cholesterol concentrations, presumably through mechanisms related to reverse cholesterol transport. The effect of dietary fats (coconut oil, butter, traditional stick margarine, soybean oil, canola oil) differing in fatty acid profile on this antiatherogenic process was assessed with respect to plasma lipids; exogenous and endogenous lecithin-cholesterol acyltransferase (LCAT), cholesterol ester transfer protein (CETP), phospholipid transfer protein (PLTP) activities; and LCAT, apolipoprotein (apo) A-I and scavenger receptor B class-1 (SR-B1) mRNA abundance. Golden-Syrian hamsters were fed a nonpurified (6.25 g/100 g fat) diet containing an additional 10 g/100 g experimental fat and 0.1 g/100 g cholesterol for 6 wk. Canola and soybean oils significantly lowered serum HDL cholesterol concentrations relative to butter. Canola oil, relative to butter, resulted in higher exogenous LCAT activity, and both soybean and canola oils significantly increased hepatic apo A-I and SR-B1 mRNA abundance. Butter, relative to margarine, coconut and soybean oils, significantly increased serum non-HDL cholesterol concentrations. Endogenous and exogenous LCAT, CETP, and PLTP activities did not differ in hamsters fed margarine or saturated fat diets, despite lower hepatic LCAT, apo A-I, and SR-B1 mRNA abundance, suggesting that changes in available substrate and/or modification to the LCAT protein may have been involved in lipoprotein changes. These results suggest that lower HDL cholesterol concentrations, as a result of canola and soybean oil feeding, may not be detrimental due to increases in components involved in the reverse cholesterol transport process in these hamsters and may retard the progression of atherosclerosis.     

Dietary long-chain polyunsaturated fatty acids from different sources affect fat and fatty acid excretions in rats.

Several sources of long-chain polyunsaturated fatty acids (LCP) have been evaluated for infant-formula supplementation. These sources differ in their chemical structure [triglyceride (TG) or phospholipid (PL)], arrangement of fatty acids on the TG or PL backbone, fatty acid composition and presence of other lipid components. All of these characteristics influence fat digestion, may affect fat and fatty acid absorption, and hence, LCP bioavailability and metabolism in infancy. The main objective of this work was to establish the influence of different dietary LCP sources on overall fat and LCP absorption in early life. We compared fat and fatty acid excretions at weaning in rats fed control diets or diets supplemented with LCP as TG or PL. Two separate experiments were conducted. In Experiment 1, weanling rats were fed for 3 wk a control diet (C1), a diet with TG from tuna and fungal oils (TF-TG) or a diet with PL from pig brain concentrate (PB-PL). In Experiment 2, weanling rats were fed for 3 wk a control diet (C2), a diet containing egg-TG (EG-TG) or a diet containing egg-PL (EG-PL). Fat, mineral and saturated fatty acid excretions in feces were higher in rats fed PB-PL compared with those fed TF-TG diet. In Experiment 2, groups did not differ in fat and mineral excretions. However, the EG-PL group had lower fecal excretions of saturated fatty acids than the C2 and EG-TG groups. The 16:1(n-7), 18:1(n-9), 18:2(n-6) and 22:6(n-3) levels in feces were higher in the EG-TG group than in the EG-PL group. In summary, total fat and LCP excretions differed among rats fed diets supplemented with LCP from different sources.     

Alpha-linolenic acid deficiency in patients on long-term gastric-tube feeding: estimation of linolenic acid and long-chain unsaturated n-3 fatty acid requirement in man

Alpha-linolenic acid deficiency is described in four adults fed by gastric tube. In plasma and erythrocytes, total lipid 20:3n-9 was slightly increased but total n-6 fatty acids, arachidonic acid, and dihomo-gamma-linolenic acid were normal. Total n-3 fatty acids, 18:3n-3, 20:5n-3, 22:5n-3, and 22:6n-3 were decreased in both plasma and erythrocytes. Patients had a slight but definite scaly dermatitis, which disappeared with essential fatty acids supplementation. Simultaneously, levels of 18:3n-3, 20:5n-3, 22:5n-3, 22:6n-3, 20:3n-9, and total n-3 fatty acids became normal while 18:2n-6, 20:3n-6, 20:4n-6, and total n-6 acids were unchanged or slightly lowered. Estimated minimal daily requirement of linolenic acid and of long-chain unsaturated n-3 acids in adults is approximately 0.2-0.3% and 0.1-0.2%, respectively, of total energy intake. Results suggest that conversion of linolenic acid to 22:6n-3 is increased in linolenic acid deficiency.     

Synthesis of long-chain polyunsaturated fatty acids in preterm newborns fed formula with long-chain polyunsaturated fatty acids

BACKGROUND: Docosahexaenoic acid (DHA) and arachidonic acid (AA) are long-chain polyunsaturated fatty acids (LCPs) that play pivotal roles in growth and neurodevelopment. OBJECTIVE: We aimed to quantify the synthesis of LCPs in preterm infants fed infant formula containing LCPs. DESIGN: Twenty-two preterm infants were randomly assigned to either the no-LCP group (fed formula without LCPs; n = 11) or the LCP group (fed formula with LCPs; n = 11). Dietary LCPs had higher (13)C content than did the endogenously synthesized LCPs, which were derived from linoleic and alpha-linolenic acids. The (13)C content of major selected plasma fatty acids was measured by using gas chromatography-isotope ratio mass spectrometry at birth and at age 1, 3, and 7 mo. Absolute LCP synthesis and the percentage of LCP synthesis relative to dietary intake were calculated. RESULTS: Percentage AA synthesis was 67.2 +/- 7.8%, 35.9 +/- 9.8%, and 29.0 +/- 10.3%, and that of DHA was 41.7 +/- 14.9%, 10.5 +/- 8.1%, and 7.4 +/- 6.2% at 1, 3, and 7 mo old, respectively. Absolute AA synthesis was 26.7 +/- 4.2, 14.4 +/- 3.9, and 11.6 +/- 4.1 mg x kg(-1) x d(-1) and that of DHA was 12.6 +/- 4.5, 3.2 +/- 2.5, and 2.3 +/- 1.9 mg x kg(-1) . d(-1) at 1, 3, and 7 mo old, respectively. AA and DHA synthesis decreased significantly (P < 0.01) with time, and AA synthesis was significantly (P < 0.01) greater than DHA synthesis. CONCLUSIONS: By this novel approach, we measured endogenous LCP synthesis in infants receiving dietary LCPs over long periods. By age 7 mo, LCP synthesis was dramatically lower in preterm infants fed LCPs.     

Monounsaturated fatty acids and cholesterol metabolism: implications for dietary recommendations

Dietary fat is known to affect serum concentrations of total and lipoprotein cholesterol. However, all components of dietary triglycerides--saturated, monounsaturated, and polyunsaturated fatty acids--do not have identical effects on serum cholesterol levels. Until recently, most attention has been given to saturated fatty acids, which raise cholesterol levels, and polyunsaturated fatty acids, which are thought by many to lower cholesterol levels. Monounsaturates in contrast have been given little attention. However, recent studies carried out in our laboratory and in others have shown that monounsaturates can have favorable effects when substituted for saturated fatty acids in the diet. In this exchange, the monounsaturates reduce low density lipoprotein (LDL) cholesterol levels, but do not lower high density lipoprotein (HDL) cholesterol levels. In contrast, an HDL-lowering action has been noted for polyunsaturates. Also, monounsaturates appear to alter lipoproteins more favorably than carbohydrates, which can raise triglycerides and lower HDL cholesterol levels. Therefore, monounsaturated fatty acids appear to have more potential for use in cholesterol-lowering diets than previously recognized.     

Perspectives on alcohol consumption: liver polyunsaturated fatty acids and essential fatty acid metabolism.

In this article, subjects diagnosed with alcoholic liver disease are shown to have lower concentrations of several polyunsaturated fatty acids (PUFAs), including 18:2n6, 18:3n6, 20:3n6, 18:3n3, 22:5n3, and 22:6n3, but not 20:4n6 and 22:4n6, nor 22:5n6, in the total lipid extracts of their livers compared with findings for specimens obtained from patients diagnosed with primary biliary cirrhosis and from control subjects. Findings of studies in animals have demonstrated that prolonged alcohol consumption reduces liver polyunsaturate content. However, the effect of ethanol on the elongation/desaturation of essential fatty acids is complex, as in vitro study results indicate that the direction of the effect of alcohol may be related to the dose of alcohol. Findings of studies in hepatocyte cell culture indicate that ethanol increased delta-5 and delta-6 desaturase activities throughout a broad concentration range. In contrast, lower liver desaturase activity has been reported in animals consuming high concentrations of alcohol (36%-40% energy) over a period of several months. Findings from in vivo isotope tracers studies in nonhuman primates and felines indicate that prolonged periods of moderate (mean consumption 2.6 g kg(-1) d(-1) and 1.2 g kg(-1) d(-1), respectively) alcohol consumption had no effect on the uptake of either linoleic (18:2n6) or alpha-linolenic (18:3n3) acids into the plasma and lead to an increased incorporation of these deuterated precursors into 20:4n6 and 22:6n3. Thus, this likely reflects a stimulated, rather than an inhibited, production of long-chain PUFAs. In numerous studies in various species, investigators have documented that alcohol consumption can increase the level of lipid peroxidation in tissues, and sustained periods of ethanol-induced peroxidation can deplete tissues of PUFAs. A hypothesis to rationalize the long-term effects of alcohol consumption on liver PUFA concentration that takes into consideration the effect of ethanol on essential fatty acid metabolism is presented.     

Short term effects of dietary medium-chain fatty acids and n-3 long-chain polyunsaturated fatty acids on the fat metabolism of healthy volunteers

Background

The amount and quality of dietary fatty acids can modulate the fat metabolism.

Objective

This dietary intervention is based on the different metabolic pathways of long-chain saturated fatty acids (LCFA), which are mostly stored in adipocytic triacylglycerols, medium-chain fatty acids (MCFA) which are preferentially available for hepatic mitochondrial β-oxidation and n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) suggested to modulate fat oxidation and storage by stimulating the peroxisomal β-oxidation. Combined dietary MCFA and n-3 LCPUFA without LCFA may synergistically stimulate fatty acid oxidation resulting in blood lipid clearance and LCFA release from adipocytes.

Design

In a short term, parallel, randomized, double-blind trial effects on the fatty acid metabolism of 10 healthy volunteers (Body Mass Index 25–30) of a formula containing 72% MCFA and 22% n-3 LCPUFA without LCFA (intake: 1.500 kcal/day; fat: 55.5% of energy) were measured in comparison to an isoenergetic formula with equal fat amount and LCFA dominated lipid profile.

Results

The plasma triacylglycerol (p < 0.1) and cholesterol (p < 0.05) content decreased in the test group. The n-3/n-6 LCPUFA (≥ C 20) ratio increased (p < 0.0001) after 4 days treatment. The LCFA content was similar in both groups despite missing LCFA in the test formula indicating LCFA release from adipocytes into the plasma. Both groups significantly reduced body weight considerably 4 kg (p < 0.01) and fat mass up to 50% of weight loss (p < 0.05).

Conclusion

Combined dietary 72% MCFA and 22% n-3 LCPUFA without LCFA stimulate the fatty acid oxidation and release from adipocytes without affecting any safety parameters measured.