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Effect of dietary n-3 fatty acids on weight gain and liver polar lipid fatty acid composition of fingerling channel catfish.

A 10-wk experiment was conducted to determine the effect of supplementing a 5% tristearin basal diet with linoleic acid [18:2(n-6)], linolenic acid [18:3(n-3)], an n-3 highly unsaturated fatty acid (n-3 HUFA) mixture, cod liver oil, corn oil or linseed oil on growth and fatty acid composition of the liver polar lipid fraction of fingerling channel catfish (Ictalurus punctatus). The lowest weight gain was observed in fish fed the basal diet. Weight gain was improved by certain levels of supplemental n-3 fatty acids. Fish fed a diet containing 2% 18:3(n-3) grew at the same rate as fish fed a diet containing 2.5% cod liver oil plus 2.5% corn oil. The best growth rate was observed in fish fed diets containing either 5% cod liver oil or 5% linseed oil. Growth rate was depressed by supplementation with 4% 18:3(n-3) or 1.25% n-3 HUFA mix. No improvement in growth rate was observed with dietary 18:2(n-6). Dietary linolenate was converted to docosahexaenoic acid [22:6(n-3)]. The ratio of 20:3(n-9) to 22:6(n-3) of the fish showing good growth was less than 0.4. The data obtained in this experiment indicate that n-3 fatty acids are essential for channel catfish and that the 18:3(n-3) or n-3 HUFA dietary requirement is 1.0-2.0% or 0.5-0.75%, respectively.

Animals↗

Quantitative analysis of fatty acid methyl esters and dimethyl acetals on a polar (free fatty acid phase) capillary column.

Separation of fatty acid methyl esters and dimethyl acetals from complex biological samples has been achieved by gas-liquid chromatography on a capillary column coated with free fatty acid phase. Response-correcting factors were determined, showing rather large variations with fatty acid length. Polyunsaturated fatty acid methyl esters were shown to have lower responses than saturated species, whereas dimethyl acetals and equivalent methyl esters were found to give similar responses. Total fatty acid and aldehyde compositions of human and simian erythrocytes were determined and compared, showing a somewhat higher level of linoleate and arachidonate, and a lower level of plasmalogens in simian erythrocytes.

Acetals↗

Augmentation of Ca2+-stimulated insulin release by glucose and long-chain fatty acids in rat pancreatic islets: free fatty acids mimic ATP-sensitive K+ channel-independent insulinotropic action of glucose.

Glucose augments Ca2+-stimulated insulin release from the pancreatic beta-cell in an ATP-sensitive K+ channel (K(ATP) channel)-independent manner. In studying the mechanisms underlying this action, we used rat pancreatic islets and examined the effects of exogenous free fatty acids (FFAs), which are precursors of long-chain acyl-CoA (LC-CoA), on KCl-induced Ca2+-stimulated insulin release. Myristate, palmitate, and stearate augmented insulin release induced by 50 mmol/l KCl in the presence of 2.8 mmol/l glucose. Added acutely, their potency was weak compared with that of glucose-induced augmentation. The FFA-induced augmentation became much greater, however, when islets were preincubated with FFAs under stringent Ca2+-free conditions (with 1 mmol/l EGTA) before the KCl stimulation. Under these conditions, 16.7 mmol/l glucose augmented 13-fold insulin release induced by 50 mmol/l KCl, whereas palmitate or myristate (both at a free concentration of 10 micromol/l) produced 5.8- and 5.2-fold augmentations. Effects of FFAs and glucose were concentration-dependent. The temporal profiles of augmentation induced by 11.1 mmol/l glucose and 10 micromol/l palmitate were similar. Glucose and palmitate caused almost identical augmentation patterns for the initial 10 min of stimulation; subsequently, glucose augmentation was better sustained than palmitate augmentation. This suggests the existence of a longer-term glucose-specific signaling moiety that cannot be mimicked by FFAs. Our results provide direct evidence that FFAs can mimic the K(ATP) channel-independent action of glucose. Taking these results together with previous results, we conclude that glucose augments Ca2+-stimulated insulin release, at least in part, by increasing malonyl-CoA and cytosolic LC-CoA. However, one or more other glucose-specific signaling molecules are required for the full expression of augmentation.

Adenosine Triphosphate↗

Dual mechanisms for telomerase inhibition in DLD-1 human colorectal adenocarcinoma cells by polyunsaturated fatty acids.

Polyunsaturated fatty acids (PUFAs) have been reported to have antitumor activity. In this study, we have tested whether telomerase might be a target for the antitumor effect of fatty acids using DLD-1 colorectal adenocarcinoma cells. In a cell-free approach, fatty acids were added directly to cell lysates, and we confirmed that increasing fatty acid unsaturation correlates with increased inhibition of telomerase activity. Using a cell culture approach, DLD-1 cells were cultured with fatty acids. In a time and dose dependent manner, EPA and DHA suppressed cellular telomerase activity and the mRNAs encoding hTERT (human telomerase reverse transcriptase) and c-myc. Based on these observations, we suggest that PUFAs inhibit telomerase activity through dual mechanisms: direct inhibition of enzymatic activity and down regulation of hTERT, one of the telomerase components.

Adenocarcinoma↗

Plasma lipoprotein fatty acids are altered by the positional distribution of fatty acids in infant formula triacylglycerols and human milk.

BACKGROUND: Triacylglycerol digestion involves hydrolysis of fatty acids esterified at the glycerol 1,3 positions by gastric and pancreatic lipase to produce 2-monoacylglycerols and unesterified fatty acids, which are then absorbed, reesterified to triacylglycerol, and secreted in chylomicrons. Palmitic acid (16:0) is predominantly esterified to the 2 position of human milk triacylglycerol but to the 1,3 positions in the oils used in infant formulas. OBJECTIVE: We aimed to determine whether the position of 16:0 in human milk and infant formula triacylglycerol influences the position of fatty acids in postprandial plasma chylomicron triacylglycerol. DESIGN: Full-term infants were fed formula with 25-27% 16:0 with either 39% of the 16:0(synthesized triacylglycerol) or 6% of the 16:0 (standard formula) esterified at the triacylglycerol 2 position, or were breast-fed (23% 16:0, 81% at the triacylglycerol 2 position) from birth to 120 d of age. Chylomicron fatty acids and plasma lipids were assessed at 30 and 120 d of age. RESULTS: Infants fed the synthesized triacylglycerol formula, standard formula, or breast milk had 15.8%,8.3%, and 28.0% 16:0 in the chylomicron triacylglycerol 2 position (P < 0.05). These results suggest that >/=50% of the dietary triacylglycerol 2-position 16:0 is conserved through digestion, absorption, and chylomicron triacylglycerol synthesis in breast-fed and formula-fed infants. Infants fed the synthesized triacylglycerol formula had significantly lower HDL-cholesterol and apolipoprotein A-I and higher apolipoprotein B concentrations than infants fed the standard formula. CONCLUSION: Dietary triacylglycerol fatty acid distribution may alter lipoprotein metabolism in young infants.

Cholesterol Esters↗

Methylene-interrupted double bond in polyunsaturated fatty acid is an essential structure for metabolism by the fatty acid chain elongation system of rat liver.

Some plant oils contain non-methylene-interrupted polyunsaturated fatty acids (NMIFAs). Pinolenic acid (all cis delta-5,9,12/18:3) and columbinic acid (trans,cis,cis delta-5,9,12/18:3) are NMIFAs that exist in pine seed oil and columbine seed oil, respectively. We investigated the double bond position of fatty acid recognized by the fatty acid chain elongation system (FACES) of rat liver using NMIFAs as experimental tools. In the total elongation assay, amounts of C2 unit chain-elongated metabolites of pinolenic acid and columbinic acid were 32% and 11%, respectively, compared to that of gamma-linolenic (all cis delta-6,9,12/18:3) as the substrate. In the condensation reaction assay, the rate limiting step of FACES, the conversion rates of pinolenic acid and columbinic acid to the corresponding C20 beta-keto fatty acids were 19% and 9% of that of gamma-linolenic acid, respectively. The formation of elongated metabolite of podocarpic acid (all cis delta-5,11,14/20:3) was only 7% of that of arachidonic acid (all cis delta-5,8,11,14/20:4). From these results it was concluded that the condensing enzyme of FACES could recognize the methylene-interrupted cis double bond structure vicinal to the carboxyl group in the fatty acid molecule.

Acetyltransferases↗

Preparation and purification of soybean lipoxygenase-derived unsaturated hydroperoxy and hydroxy fatty acids and determination of molar absorptivities of hydroxy fatty acids.

A method was developed for the preparation and purification of polyunsaturated hydroperoxy and hydroxy fatty acids from 18:2n-6, 18:3n-6, 18:3n-3, 20:3n-6, 20:3n-3, and 20:4n-6 with soybean lipoxygenase. This method involved incubation of unsaturated fatty acids in Tris-HCl buffer with soybean lipoxygenase and extraction of reaction products on C18 solid-phase columns. The yields of conversion of fatty acid substrate to oxygenated products were in all cases greater than or equal to 95%. C18 solid-phase extracted reaction products were purified by C18 HPLC, yielding 3-4 mg of products with purities of greater than or equal to 98%. Purified polyunsaturated hydroxy fatty acids were characterized by HPLC and mass spectral analysis and showed absorption spectra with maximum absorption occurring between 234.5 and 237.5 nm due to the presence of a conjugated diene function. Polyunsaturated hydroxy fatty acid potassium salts were converted to (4-bromobenzoyl)methyl esters by reaction with 2,4'-dibromoacetophenone in the presence of 18-crown-6. Molar absorptivities for the conjugated diene functions were determined by relating their absorbance to the absorbance contributed by the 4-bromobenzoyl chromophore and its molar absorption intensity of 17.6 X 10(3) (M.cm)-1. The molar absorptivities determined for 13-OH-9,11-18:2, 13-OH-6,9,11-18:3, 13-OH-9,11,15-18:3, 15-OH-11,13-20:2, 15-OH-8,11,13-20:3, 15-OH-11,13,17-20:3, and 15-OH-5,8,11,13-20:4 ranged from 23.2 x 10(3) to 24.6 x 10(3) (M.cm)-1. The molar absorbtivity values of 18.8 x 10(3) and 20.3 x 10(3) (M.cm)-1 determined for commercial, chemically synthesized 12-OH-5,8,10,14-20:4 [12-(S)-hydroxyeicosa-5,8,10,14-tetraenoic acid (12(S)-HETE)] and 5-OH-6,8,11,14-20:4 ((+/-)-5-HETE) were lower than that of soybean lipoxygenase-derived 15-OH-5,8,11,13-20:4 (15-HETE), which exhibited a molar absorptivity of 23.3 x 10(3) (M.cm)-1. The molar absorptivity values determined for 5-, 12-, and 15-HETE are considerably lower than 30.5 x 10(3) (M.cm)-1, which was reported previously.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Intersubunit transfer of fatty acyl groups during fatty acid reduction.

Fatty acid reduction in Photobacterium phosphoreum is catalyzed in a coupled reaction by two enzymes: acyl-protein synthetase, which activates fatty acids (+ATP), and a reductase, which reduces activated fatty acids (+NADPH) to aldehyde. Although the synthetase and reductase can be acylated with fatty acid (+ATP) and acyl-CoA, respectively, evidence for acyl transfer between these proteins has not yet been obtained. Experimental conditions have now been developed to increase significantly (5-30-fold) the level of protein acylation so that 0.4-0.8 mol of fatty acyl groups are incorporated per mole of the synthetase or reductase subunit. The acylated reductase polypeptide migrated faster on sodium dodecyl sulfate-polyacrylamide gel electrophoresis than the unlabeled polypeptide, with a direct 1 to 1 correspondence between the moles of acyl group incorporated and the moles of polypeptide migrating at this new position. The presence of 2-mercaptoethanol or NADPH, but not NADP, substantially decreased labeling of the reductase enzyme, and kinetic studies demonstrated that the rate of covalent incorporation of the acyl group was 3-5 times slower than its subsequent reduction with NADPH to aldehyde. When mixtures of the synthetase and reductase polypeptides were incubated with [3H] tetradecanoic acid (+ATP) or [3H]tetradecanoyl-CoA, both polypeptides were acylated to high levels, with the labeling again being decreased by 2-mercaptoethanol or NADPH. These results have demonstrated that acylation of the reductase represents an intermediate and rate-limiting step in fatty acid reduction. Moreover, the activated acyl groups are transferred in a reversible reaction between the synthetase and reductase proteins in the enzyme mechanism.

Acyl Coenzyme A↗

[Comparative bioavailability of eicosapentaenoic acid and docasahexaenoic acid from triglycerides, free fatty acids and ethyl esters in volunteers].

Comparative Bioavailability of Eicosapentaenoic Acid and Docosahexaenoic Acid from Triglycerides, Free Fatty Acids and Ethyl Esters in Volunteers. The bioavailability of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from triglycerides, free fatty acids and ethyl esters was investigated in 8 female volunteers in a randomized triple cross-over trial with baseline control. EPA/DHA was administered in capsules in form of triglycerides (1.68/0.72 g), free fatty acids (1.35/1.065 g) and ethyl esters (1.86/1.27 g). The resulting EPA/DHA plasma levels were determined and evaluated. The mean relative bioavailability of EPA/DHA compared to triglycerides was 186/136% from free fatty acids and 40/48% from ethyl esters. Maximal plasma levels were about 50% higher with free fatty acids and about 50% lower with ethyl esters as compared to triglycerides. The tolerability of the free fatty acids was much worse than that of triglycerides and ethyl esters. The main side effect was eructation.

Adult↗

Supplementation of omega-3 fatty acids in parenteral nutrition beneficially alters phospholipid fatty acid pattern.

BACKGROUND: The clinical safety and the uptake of omega-3 polyunsaturated fatty acids (PUFA) into the serum phospholipids and erythrocyte membranes after administration of fish-oil-supplemented parenteral nutrition (PN) was investigated in colorectal surgical patients. METHODS: Forty patients undergoing colorectal surgery (n = 40) and with an indication for PN were enrolled in a prospective, double-blind, randomized study to receive an omega-3 PUFA-supplemented 20% lipid emulsion (Lipoplus; B. Braun Melsungen, Melsungen, Germany; test group, n = 19) for 5 days postoperatively. The control group received a standard 20% fat emulsion (Lipofundin MCT/LCT, B. Braun Melsungen, Melsungen, Germany, control group, n = 21). Clinical outcome parameters and safety were assessed by means of adverse events recording clinical parameters and hematologic analyses. The contents of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), as well as arachidonic acid (AA), in phospholipid fractions in plasma and in erythrocytes were analyzed preoperatively, on postoperative days 1, 6, and 10 using liquid gas chromatography. RESULTS: Both fat emulsions were well tolerated, and none of the adverse events was considered to be related to treatment. Postoperative infectious complications occurred in 4 patients of the omega-3 PUFA group vs 7 patients in the control group. As compared with the control group, the omega-3 PUFA group had significantly increased levels of EPA in the membranes of the erythrocytes in postoperative day 6 (2.0% +/- 0.9% vs 0.8% +/- 0.5% fatty acid methyl esters, [FAME]) and postoperative day 10 (2.1% +/- 0.8% vs 0.9% +/- 0.7% FAME, p < .05). Also, the EPA levels in the serum phospholipids were significantly higher than in the control group on the same postoperative days (7.0% +/- 2.6% vs 1.3% +/- 0.8% and 3.6% +/- 1.0% vs 1.0% +/- 0.4% FAME, p < .05). The DHA levels in the serum phospholipids were significantly higher in the omega-3 PUFA group compared with the control on postoperative days 6 and 10 (11.8% +/- 1.9% vs 8.4% +/- 1.5% and 11.2% +/- 1.6% vs 8.5% +/- 1.4% FAME, p < .05). AA levels were not significantly different in the both groups. CONCLUSIONS: Omega-3-fatty-acids-supplemented fat emulsions for parenteral administration are safe and very well tolerated. This study demonstrates that parenteral administration of omega-3-PUFA-enriched fat emulsions leads to increased incorporation of EPA and DHA into phospholipids in serum and erythrocytes, whereas AA levels remain unchanged. Thus, postoperative parenteral administration of omega-3-PUFA-enriched lipid emulsions could have an impact on the postoperative inflammatory response after abdominal surgery and could be used in standard postoperative care when PN is indicated.

Adult↗

Application of high-performance liquid chromatography of plasma fatty acids as their phenacyl esters to evaluate splanchnic and renal fatty acid balance in vivo.

Plasma fatty acids from renal and hepatic veins, and arterialized hand vein obtained in 20 subjects before and after insulin infusion were separated by reversed-phase high-performance liquid chromatography following phenacyl esterification. Separation and quantification over the range 1.0-100 nmol per injection of nine fatty acids was achieved within 60 min using [2H31]palmitic acid as internal standard. Analytical recoveries were greater than 90% and the intra- and inter-assay coefficients of variation were less than 2.5 and 4.0%, respectively. Following insulin infusion, net splanchnic uptake of total fatty acids decreased from 3.0+/-0.3 to 1.0+/-0.1 micromol/kg min (p<0.01), whereas net renal balance remained neutral (-0.04+/-0.04 vs. -0.06+/-0.03 micromol/kg min, p=N.S.). Individual fatty acid balance varied from a low of 0.012+/-0.005 (myristic acid) to a high of 0.95+/-0.08 (oleic acid) micromol/kg min across the splanchnic tissues and from 0.005+/-0.002 (stearic acid) to 0.21+/-0.1 (oleic acid) micromol/kg min across the kidney. There is a substantial diversity in changes in plasma concentration and regional balance of individual fatty acid during short-term fasting and hyperinsulinemia. This method is simple, accurate, and can be applied to assess individual fatty acid metabolism in vivo.

Chromatography, High Pressure Liquid↗

Identification and expression of a rat fatty acid elongase involved in the biosynthesis of C18 fatty acids.

A major part of the palmitic acid (C16:0) generated by fatty acid synthase is converted into stearic acid (C18:0) via carbon chain elongation. Here, we describe the cloning and expression of a rat hepatic enzyme, rELO2, responsible for the elongation of C16:0, presumably at the condensing reaction. Heterologous expression experiments in a yeast, Saccharomyces cerevisiae, demonstrated the elongation activity of rELO2 on C16:0 and to a lesser extent, C18:0 and fatty acids with low desaturation degree. This was distinct from that rELO1, a rat homolog of HELO1, which preferably catalyzed the elongation of mono- and polyunsaturated fatty acids of C16-C20. The Northern analysis showed that the expression of rELO2, but not rELO1, in hepatocytes was activated by the cycles of fasting and refeeding rats on a fat-free diet. Under these conditions, the rELO1 was expressed constitutively in various tissues but the rELO2 transcripts were detected predominantly in liver.

Acetyltransferases↗

Level of polyunsaturated fatty acids and the n-6 to n-3 polyunsaturated fatty acid ratio in the rat diet alter serum lipid levels and lymphocyte functions.

In order to further examine the effects of dietary polyunsaturated fatty acids (PUFA) upon blood lipid levels and lymphocyte functions, weanling rats were fed for 6 weeks on high fat (178 g/kg) diets which differed in the ratio of n-6:n-3 PUFA (100, 20, 10, 5, 1) and in the absolute level of PUFA (17.5 or 35 g/100 g fatty acids). The n-6:n-3 PUFA ratio of the diets was decreased by replacing linoleic acid with alpha-linolenic acid while the PUFA content of the diets was decreased by replacing PUFA with palmitic acid. Serum cholesterol concentrations decreased as the n-6:n-3 PUFA ratio of the low PUFA diet decreased. The ex vivo proliferation of spleen lymphocytes from rats fed the low PUFA diets decreased as the n-6:n-3 PUFA ratio of the diet decreased; the proliferation of spleen lymphocytes from high PUFA-fed rats was less affected by the n-6:n-3 PUFA ratio of the diet. Natural killer cell activity was lower for spleen lymphocytes from rats fed high PUFA diets with n-6:n-3 PUFA ratios of 100 or 20 than for those from rats fed low PUFA diets with these ratios. The natural killer cell activity of spleen lymphocytes decreased as the n-6:n-3 PUFA ratio of the low PUFA diet decreased. These findings indicate that dietary alpha-linolenic acid has significant blood lipid-lowering and immunomodulatory effects in rats, but that the effect is dependent upon the total PUFA content of the diet. The ratios of linoleic and alpha-linolenic acids to other fatty acids (e.g. palmitic, oleic) are important in determining the precise effect of manipulations of the fatty acid composition of the diet.

Analysis of Variance↗

Effects of dietary supplementation of saturated fatty acids and of n-6 or n-3 polyunsaturated fatty acids on plasma and red blood cell membrane phospholipids and deformability in weanling guinea pigs.

The fatty acid composition of plasma cholesteryl esters, plasma phospholipids, red blood cell (RBC) membrane phosphatidylcholine (corresponding to the outer membrane leaflet), and phosphatidylethanolamine (corresponding to the inner membrane leaflet) was investigated in weanling guinea pigs fed with diets of cacao (saturated fatty acids), sunflower oil [n-6 polyunsaturated fatty acids (PUFA)] or fish oil (n-3 PUFA) for 20 wk. RBC deformation was measured by means of a cell-transit analyzer (filtration) and a cone-plate rheoscope. The contents of saturated fatty acids in plasma phospholipids and RBC membrane leaflets were similar in all three groups. Diets with sunflower oil resulted in a high content of linoleic acid in plasma cholesteryl esters and in the outer leaflet of RBC membranes. Fatty acids of fish oil were mainly incorporated in plasma phospholipids and in the inner leaflet of RBC membranes. The arachidonic acid content was high in all groups in the plasma phospholipids and in the inner leaflet. The n-6 and n-3 PUFA were mainly incorporated in the inner leaflet. In all groups the polyunsaturated/saturated fatty acid ratio and the total PUFA content were similar in the inner RBC membrane. The RBC filtration times and the RBC deformation indices were not affected by the dietary treatment.

Animals↗

[Dietary habits and serum fatty acid compositions of women college students--changes in serum lipids and fatty acids by dietary education].

To obtain fundamental information for prevention of coronary heart disease in young adults, frequency of dietary intake, blood lipid and serum fatty acid compositions were examined for 114 female students. The relationship of selected food intake to serum fatty acid composition was also examined. Results of a nutritional survey were used to identify students who had a frequency of fish intake of "none" or "1-2 times/week" from whom random selection into two groups was accomplished: control group (n = 31) and education group (n = 31). The education group received a recommendation for increasing fish intake for 3 months. The effect of the education program was evaluated by examination of blood lipids, serum fatty acid compositions and frequency of dietary intake. Fifty-four percent of the students reported "none" or "1-2 times/week" for the frequency of fish intake, and 76% of them reported "1 and more times/day" for oil intake. The proportion of serum saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids were 28.9%, 24.4%, 46.8%, respectively. Of the polyunsaturated fraction, 41.4% was omega 6-polyunsaturated fatty acids, and that of omega 3-polyunsaturated fatty acids was 5.4%. The omega 3/omega 6 ratio was 0.13. Serum omega 3-polyunsaturated fatty acids was directly related to frequency of fish intake, and serum omega 6-polyunsaturated fatty acid, especially linoleic acid, was directly related to frequency of oil intake. After a 3-month education program, the frequency of fish intake and meat intake increased, while frequency of oil intake decreased in the education group. Serum omega 3-polyunsaturated fatty acid (in particular eicosapentaenoic acid, docosahexaenoic acid) increased in the education group, but not in the control group. The omega 3/omega 6 ratio increased from 0.13 to 0.18 in the education group. These results indicate that dietary education for fish intake is effective in increasing serum omega 3-polyunsaturated fatty acids, and the omega 3/omega 6 ratio for female students with initial low intake of fish and a high intake of omega 6-polyunsaturated fatty acids.

Adult↗

Risk of colorectal cancer is linked to erythrocyte compositions of fatty acids as biomarkers for dietary intakes of fish, fat, and fatty acids.

Consumption of fish rich in n-3 polyunsaturated fatty acids (PUFAs), such as docosahexaenoic acid, is suggested to reduce colorectal cancer risk through inhibition of the arachidonic acid (AA) cascade related to tumorigenesis and cell proliferation. High intake of saturated fatty acids (SFAs) may increase the risk. To examine associations between colorectal cancer risk and fatty acid compositions in erythrocyte membranes, as biomarkers for dietary intakes of fish, fat, and fatty acids, we conducted a case-control study with 74 incident cases and 221 noncancer controls (matched by age, sex, and season of sample collection). Erythrocyte fatty acids were measured using an accelerated solvent extraction and a gas-liquid chromatography. Colorectal cancer had no association with dietary intakes of meat, fish, fat, and fatty acids. However, the risk was inversely associated with erythrocyte compositions of docosahexaenoic acid, AA, and PUFAs [the highest to the lowest tertile, odds ratios, 0.36, 0.42, and 0.15; 95% confidence intervals, 0.14-0.93, 0.18-0.95, and 0.05-0.46; P(trend) < 0.05, respectively] and positively with those of palmitic acid, SFAs, and the ratio of SFAs/PUFAs (odds ratios, 6.46, 8.20, and 9.45; 95% confidence intervals, 2.41-17.26, 2.86-23.52, and 2.84-31.43; P(trend) < 0.005, respectively). In conclusion, we could clearly show decreased and increased risks for colorectal cancer related to PUFAs and SFAs compositions in erythrocyte membranes, respectively, but further research is needed to investigate the discrepancy between our findings and the generally accepted role of the AA cascade.

Adult↗

Inactivation of the peroxisomal multifunctional protein-2 in mice impedes the degradation of not only 2-methyl-branched fatty acids and bile acid intermediates but also of very long chain fatty acids.

According to current views, peroxisomal beta-oxidation is organized as two parallel pathways: the classical pathway that is responsible for the degradation of straight chain fatty acids and a more recently identified pathway that degrades branched chain fatty acids and bile acid intermediates. Multifunctional protein-2 (MFP-2), also called d-bifunctional protein, catalyzes the second (hydration) and third (dehydrogenation) reactions of the latter pathway. In order to further clarify the physiological role of this enzyme in the degradation of fatty carboxylates, MFP-2 knockout mice were generated. MFP-2 deficiency caused a severe growth retardation during the first weeks of life, resulting in the premature death of one-third of the MFP-2(-/-) mice. Furthermore, MFP-2-deficient mice accumulated VLCFA in brain and liver phospholipids, immature C(27) bile acids in bile, and, after supplementation with phytol, pristanic and phytanic acid in liver triacylglycerols. These changes correlated with a severe impairment of peroxisomal beta-oxidation of very long straight chain fatty acids (C(24)), 2-methyl-branched chain fatty acids, and the bile acid intermediate trihydroxycoprostanic acid in fibroblast cultures or liver homogenates derived from the MFP-2 knockout mice. In contrast, peroxisomal beta-oxidation of long straight chain fatty acids (C(16)) was enhanced in liver tissue from MFP-2(-/-) mice, due to the up-regulation of the enzymes of the classical peroxisomal beta-oxidation pathway. The present data indicate that MFP-2 is not only essential for the degradation of 2-methyl-branched fatty acids and the bile acid intermediates di- and trihydroxycoprostanic acid but also for the breakdown of very long chain fatty acids.

3-Hydroxyacyl CoA Dehydrogenases↗