bluuebunny/crossref_metadata_2025 huggingface dataset:
Dietary n−3 polyunsaturated fatty acids increase T‐lymphocyte phospholipid mass and acyl‐CoA binding protein expression
Authors: Collison Lauren W. , Collison Robert E. , Murphy Eric J. , Jolly Christopher A.
Published: November 2006

Dietary flaxseed oil, which is enriched in α‐linolenic acid, and fish oil, which is enriched inEPA and DHA, possess anti‐inflammatory properties when compared with safflower oil, which is enriched in linoleic acid. The influence of flaxseed oil and fish oil feeding on lipid metabolism in T‐lymphocytes is currently unknown. This study directly compared the effects of feeding safflower oil, flaxseed oil, and fish oil for 8 wk on splenic T‐lymphocyte proliferation, phospholipid mass, and acyl‐CoA binding protein expression in the rat. The data show that both flaxseed oil and fish oil increased acyl‐CoA binding protein expression and phosphatidic acid mass in unstimulated T‐lymphocytes when compared with safflower oil feeding. Fish oil feeding increased cardiolipin mass, whereas flaxseed oil had no effect. After stimulation, flaxseed oil and fish oil blunted T‐lymphocyte interleukin‐2 production and subsequent proliferation, which was associated with the lack of incraased acyl‐CoA binding protein expression. The results reported show evidence for a novel mechanism by which dietary flaxseed oil and fish oil suppress T‐lymphocyte proliferation via changes in acyl‐CoA binding protein expression and phospholipid mass.
Milk fat synthesis is unaffected by abomasal infusion of the conjugated diene 18∶3 isomers cis‐6, trans‐10, cis‐12 and cis‐6, trans‐8, cis‐12
Authors: Sæbø A. , Perfield J. W. , Delmonte P. , Yurawecz M. P. , Lawrence P. , Brenna J. T. , Bauman D. E.
Published: November 2006

It has been previously established that trans‐10, cis‐12 CLA is a potent inhibitor of milk fat synthesis. Although the mechanism of this action is not completely understood, it has been speculated that eicosanoid‐like metabolites of this isomer formed by the activity of tissue desaturases may be responsible for its activity. The objective of this study was to investigate the effects of an enrichment containing an 18∶3 conjugated diene, produced in the metabolism of trans‐10, cis‐12 CLA, on milk fat synthesis. Three rumen‐fistulated Holstein cows (210±8 d in milk) were randomly assigned in a 3×3 Latin square experiment. Treatments were (i) control, (ii) trans‐10, cis‐12 CLA supplement (2.1 g/d; positive control), (iii) enrichment providing two conjugated diene 18∶3 isomers (2.6 g/d of cis‐6, trans‐10, cis‐12 and 4.0 g/d of cis‐6, trans‐8, cis‐12) and trans‐10, cis‐12 CLA (2.1 g/d). Treatments were abomasally infused for 5 d at 4‐h intervals, and there was a 7‐d interval between periods. Milk yield, dry matter intake, and milk protein yield were unaffected by treatments. In contrast, the trans‐10, cis‐12 CLA supplement reduced milk fat yield by 27%, whereas the supplement enriched with conjugated diene 18∶3 isomers (treatment iii) had no effect on milk fat yield beyond that attributable to its trans‐10, cis‐12 CLA content. The transfer efficiency of trans‐10, cis‐12 CLA into milk fat was 25 and 24% for treatments ii and iii, respectively. At the same time, the abomasally infused conjugated diene 18∶3 isomers were transferred to milk fat with an efficiency of 33 and 41% for cis‐6, trans‐10, cis‐12 and cis‐6, trans‐8, cis‐12 18∶3, respectively. Overall, short‐term abomasal infusion of the conjugated diene 18∶3 isomers had no effect on milk fat synthesis, thereby offering no support for an involvement of metabolies of trans‐10, cis‐12 CLA in the regulation of milk fat synthesis.
GC‐MS structural characterization of fatty acids from marine aerobic anoxygenic phototrophic bacteria
Authors: Rontani J. ‐F. , Christodoulou S. , Koblizek M.
Published: November 2006

The FA composition of 12 strains of marine aerobic anoxygenic phototrophic bacteria belonging to the genera Erythrobacter, Roseobacter, and Citromicrobium was investigated. GC‐MS analyses of different types of derivatives were performed to determine the structures of the main FA present in these organisms. All the analyzed strains contained the relatively rare 11‐methyloctadec‐12‐enoic acid, and three contained 12‐methyl‐octadec‐11‐enoic acid, which has apparently never been reported before. High amounts of the very unusual octadeca‐5,11‐dienoic acid were present in 9 of the 12 strains analyzed. A FA containing a furan ring was detected in three strains. Analytical data indicated that this FA was 10,13‐epoxy‐11‐methyloctadeca‐10,12‐dienoic acid. A very interesting enzymatic peroxidation of the allylic carbon 10 of cis‐vaccenic acid was observed in three strains. Deuterium labeling and GC‐MS analyses enabled us to demonstrate that this enzymatic process involves the initial dioxygenase‐mediated formation of 10‐hydroperoxyoctadec‐11(cis)‐enoic acid, which is then isomerized to 10‐hydroperoxyoctadec‐11(trans)‐enoic acid and converted to the corresponding hydroxy‐acids and oxoacids. Different biosynthetic pathways were proposed for these different compounds.
Preparation and fractionation of conjugated trienes from α‐linolenic acid and their growth‐inhibitory effects on human tumor cells and fibroblasts
Authors: Igarashi Miki , Miyazawa Teruo
Published: November 2006

Conjugated α‐linolenic acid (ClnA) was prepared from α‐linolenic acid (9,12,15–18∶3n−3, LnA) by alkaline treatment; we fractionated CLnA into three peaks by reversed‐phase column‐HPLC as evidenced by monitoring absorbance at 205, 235, and 268 nm. Peak I was a conjugated dienoic FA derived from LnA, whereas Peaks II and III were conjugated trienoic LnA. Proton NMR analysis showed that Peak III consisted of the all‐trans isomer. The methylated Peak III was further divided into five peaks (Peaks IV–VIII) by silver ion column‐HPLC. Peak V, a major constituent in the Peak III fraction, was identified as conjugated 10t,12t,14t‐LnA by GC‐EIMS and 1H NMR analysis. Peaks III and V, which consisted of conjugated all‐trans trienoic LnA, had stronger growth‐inhibitory effects on human tumor cell lines than the other collected peaks and strongly induced lipid peroxidation as compared with Peaks I, II, and LnA. We propose that conjugated all‐trans trienoic FA have the strongest growth‐inhibitory effect among the conjugated trienoic acids and conjugated dienoic acids produced by alkaline treatment of α‐LnA, and that this effect is mediated by lipid peroxidation.
Astonishing diversity of natural surfactants: 5. Biologically active glycosides of aromatic metabolites
Authors: Dembitsky Valery M.
Published: November 2006

This review article presents 342 aromatic glycosides, isolated from and identified in plants and microorganisms, that demonstrate different biological activities. They are of great interest, especially for the medicinal and/or pharmaceutical industries. These biologically active natural sufactants are good prospects for the future chemical preparation of compounds useful as antioxidant, anticancer, antimicrobial, and antibacterial agents. These glycosidic compounds have been classified into several groups, including simple aromatic compounds, stilbenes, phenylethanoids, phenylpropanoids, naphthalene derivatives, and anthracene derivatives.
Effects of the individual isomers cis‐9,trans‐11 vs. trans‐10,cis‐12 of conjugated linoleic acid (CLA) on inflammation parameters in moderately overweight subjects with LDL‐phenotype B
Authors: Ramakers Julian D. , Plat Jogchum , Sébédio Jean‐Louis , Mensink Ronald P.
Published: November 2006

Immune‐modulating effects of CLA have been reported in animals, but results are inconsistent. In humans, CLA has shown no effects or only minor effects on immune function. The objective of this study was to evaluate the immune‐modulating effects of 3 g cis‐9,trans‐11 (c9,t11) vs. trans‐10,cis‐12 (t10,c12) CLA isomers in a population with a high risk of coronary heart disease characterized by moderate overweight (body‐mass index, 25–32.5 kg/m2) in combination with LDL‐phenotype B (≥35% small LDL cholesterol, density≥1.040 g/mL). After a run‐in period of 1 wk, 42 men and women were randomly allocated to the c9,t11 CLA group, the t10,c12 CLA group, or the placebo group. Effects of 13 wk of consumption of 3 g of CLA isomers on cytokine production by ex vivo lipopolysaccharide (LPS)‐stimulated peripheral blood mononuclear cells (PBMC) and whole blood, and on plasma C‐remononuclear protein (CRP) concentrations were evaluated. To generate hypotheses for future studies, protein expression patterns of 42 cytokines, chemokines, and growth factors were evaluated with an antibody array in pooled, nonstimulated, fasting plasma samples. LPS induced interleukin (IL)‐6, IL‐8, and tumor necrosis factor‐α production by PBMC, and whole blood as well as plasma CRP concentrations were not significantly changed by the c9,t11, and the t10,c12 CLA isomers. The cytokine expression profile in nonstimulated plasma suggested that both CLA isomers induced a specific inflammatory signature, in which the c9,t11 CLA group showed more activity in terms of numbers of proteins regulated. We conclude that daily consumption of 3 g of c9,t11 or t10,c12 CLA isomer did not affect LPS‐stimulated cytokine production by PBMC or whole blood and plasma CRP levels. Inflammatory signatures in fasting, nonstimulated plasma as determined by an antibody array may indicate enhanced immune function by both CLA isomers.
Dietary sitostanol and campestanol: Accumulation in the blood of humans with sitosterolemia and xanthomatosis and in rat tissues
Authors: Connor William E. , Lin Don S. , Pappu Anuradha S. , Frohlich Jiri , Gerhard Glenn
Published: November 2006

Dietary sitostanol has a hypocholesterolemic effect because it decreases the absorption of cholesterol. However, its effects on the sitostanol concentrations in the blood and tissues are relatively unknown, especially in patients with sitosterolemia and xanthomatosis. These patients hyperabsorb all sterols and fail to excrete ingested sitosterol and other plant sterols as normal people do. The goal of the present study was to examine the absorbability of dietary sitostanol in humans and animals and its potential long‐term effect. Two patients with sitosterolemia were fed the margarine Benecol (McNeill Nutritionals, Ft. Washington, PA), which is enriched in sitostanol and campestanol, for 7–18 wk. Their plasma cholesterol levels decreased from 180 to 167 mg/dL and 153 to 113 mg/dL, respectively. Campesterol and sitosterol also decreased. However, their plasma sitostanol levels increased from 1.6 to 10.1 mg/dL and from 2.8 to 7.9 mg/dL, respectively. Plasma campestanol also increased. After Benecol withdrawal, the decline in plasma of both sitostanol and campestanol was very sluggish. In an animal study, two groups of rats were fed high‐cholesterol diets with and without sitostanol for 4 wk. As expected, plasma and liver cholesterol levels decreased 18 and 53%, respectively. The sitostanol in plasma increased fourfold, and sitostanol increased threefold in skeletal muscle and twofold in heart muscle. Campestanol also increased significantly in both plasma and tissues. Our data indicate that dietary sitostanol and campestanol are absorbed by patients with sitosterolemia and xanthomatosis and also by rats. The absorbed plant stanols were deposited in rat tissues. Once absorbed by sitosterolemic patients, the prolonged retention of sitostanol and campestanol in plasma might increase their atherogenic potential.
Monitoring the oxidation of docosahexaenoic acid in lipids
Authors: Lyberg Ann‐Marie , Fasoli Ezio , Adlercreutz Patrick
Published: November 2006

The oxidation of free DHA, DHA mixed with PC, and DHA incorporated into PC, PE, or TG was evaluated to determine which lipid provided DHA with the best protection against oxidation. DHA was either situated at the sn‐1 position, sn‐2 position, or both positions of the phospholipid, whereas the TG contained DHA at all positions. All lipids were incubated as bulk lipids, in chloroform, or as an emulsion in contact with air at 25–30°C for 28 d. Since DHA, which is highly sensitive to oxidation, has a great impact on our health and is desired as a food additive, the stability of this FA is of great importance. This study was mainly focused on the primary oxidation products, which were monitored as eight monohydroperoxy‐DHA isomer groups, the total amount of polyhydroperoxides, and the PV. However, a measure of secondary oxidation products, the carbonyl value, was also monitored. We found that DHA was most protected against hydroperoxide formation when it was incorporated at one position of either PC or PE. In these lipids, hydroperoxide formation at carbon atoms 4, 7, 8, and 11 was completely prevented. DHA mixed with PC was also protected, although to a lesser extent, and all hydroperoxide isomers were detected. In contrast, PC and TG containing DHA at all positions should be avoided, since they were highly oxidized.
Influence of diet on the kinetic behavior of hepatic carnitine palmitoyltransferase I toward different acyl CoA esters
Authors: Power Glen W. , Cake Max H. , Newsholme Eric A.
Published: November 2006

The influence of diet on the kinetics of the overt form of rat liver mitochondrial carnitine palmitoyltransferase (CPT I; EC 2.3.1.21) was studied using rats fed either a low‐fat diet (3% w/w fat), or diets which were supplemented with either olive oil (OO), safflower oil (SO) or menhaden (fish) oil (MO) to 20% w/w of fat (high fat diets). When animals were fed each of these four diets for 10 days, the order of the apparent maximal activity (Vmax) of CPT I toward various individual fatty acyl CoA, when measured under a fixed molar ratio of acyl CoA/albumin, was 16∶1n−7>18∶1n−9>18∶2n−6>16∶0>22∶6n−3, and was thus not affected by the fat composition of the diet. However, in all but one case, the SO and MO diets elicited a higher Vmax for each substrate than either the LF diet or the high fat OO diet. The apparent K0.5 for the different acyl CoA esters was generally lowest in LF‐fed animals, and highest in those fed the high‐fat SO diet. Moreover, when compared with the situation of animals fed high‐fat diets, the K0.5 values of CPT I in LF‐fed animals for palmitoyl CoA and oleoyl CoA were low. This possession by CPT I of a high “affinity” toward these nonessential fatty acyl CoAs, but a lower “affinity” toward linoleoyl CoA, the ester of an essential fatty acid, may enable this latter fatty acid to be spared from oxidation when its concentration in the diet is low. The data also emphasize that palmitoleoyl CoA, if available in the diet, is likely to be utilized by CPT I at a high rate.
Lipid composition of cultured endothelial cells in relation to their growth
Authors: Cansell Maud , Gouygou Jean‐Paul , Jozefonvicz Jacqueline , Letourneur Didier
Published: November 2006

Human endothelial cells in culture were examined in different growth conditions. The human endothelial cell line, EA.hy 926 cell line, was used and cells were studied either in exponential growth phase, at confluence, or growth‐arrested by serum deprivation. Phospholipids were separated and analyzed by high‐performance thin‐layer chromatography, and their fatty acids were quantified by gas‐liquid chromatography. No significant differences in the phospholipid distributions were found between exponentially growing and confluent endothelial cells in which phosphatidylcholine (PC) represented the major phospholipid. In comparison, serum‐deprived cells exhibited higher proportions of sphingomyelin and lower content of PC. We also found that among the total lipids, cholesterol level for dividing endothelial cells was lower than for cells growth‐arrested either by serum deprivation or by contact inhibition at confluence. The global fatty acid distribution was not affected by the growth conditions. Thus, oleate (18∶1n−9 and 18∶1n‐7), palmitate (C16∶0), and stearate (C18∶0) were the main components of endothelial cell membranes. However, the fatty acid distributions obtained from each phospholipid species differed with the growth status. Altogether, the data indicated that subtle modulations of endothelial cell metabolism appear upon cell growth. The resulting membrane‐dependent cellular functions such as cholesterol transport and receptor activities can be expected to be relevant for lipid trafficking within the vessel wall in vitro and in vivo.
Effect of radiotherapy and chemotherapy on composition of tumor membrane phospholipids
Authors: Street James C. , Koutcher Jason A.
Published: November 2006

Phospholipid extracts were made of a murine mammary adenocarcinoma implanted in the dorsum of the foot of C3H/He mice before and 96 h after 17 Gy irradiation or 150 mg/kg cyclophosphamide. Extracts of untreated tumors, which had grown for a further 96 h, were also studied. Although previous studies have shown significant changes in the precursors and catabolites of phosphatidylcholine and phosphatidylethanolamine following therapy, 31P nuclear magnetic resonance analysis of extracts showed no changes in these membrane constituents and other observed phospholipid species. A significant decrease in 1‐alkyl‐2‐acyl‐sn‐glycero‐3‐phosphocholine, however, was observed 96 h following cyclophosphamide treatment.
Dietary very long chain fatty acids directly influence the ratio of tetracosenoic (24∶1) to tetracosanoic (24∶0) acids of sphingomyelin in rat liver
Authors: Bettger W. J. , Blackadar C. B.
Published: November 2006

Twenty‐one groups of weanling male Wistar rats were fed semipurified diets containing 5% (w/w) of different dietary fats. After 2 wk, liver sphingomyelin (SM) fatty acid composition was determined. The ratio of 24∶1 to 24∶0 in liver SM varied over a tenfold range in response to dietary fat type. Stepwise multiple regression analysis indicated that dietary 24∶1, 24∶0, and 22∶1 were the most significant factors in predicting the 24∶1/24∶0 ratio of liver SM. The mathematical relation between the dietary fatty acid composition and liver SM 24∶1/24∶0 was y=1.88 (24∶1)−1.49 (24∶0)+0.21 (22∶1)+0.01 (18∶1)+0.26, r2=0.95, P<0.0001. These results were confirmed by a second experiment in which the rats were fed olive oil‐based diets supplemented with various fatty acid ethyl esters.
Androgen regulation of lung lipids in the male rat
Authors: Ojeda Marta S. , Gomez Nidia , Giménez María S.
Published: November 2006

The aim of this study was to determine whether or not testosterone regulates the lipid concentration in rat lung tissue. Rats were either sham‐operated controls, castrated, or castrated and injected with testosterone. Twenty‐one days after castration, we observed in relation to the control: (i) Total lipids, phospholipids, and total cholesterol increased, while triglycerides decreased in whole lung. (ii) Phospholipid concentration increased in microsomes, lamellar bodies, and alveolar macrophages, but it decreased in extracellular surfactant. (iii) On a percentage basis, the concentration of phosphatidylcholine increased in microsomes, lamellar bodies, and alveolar macrophages, and it decreased in extracellular surfactant. (iv) Protein concentration decreased in extracellular surfactant and increased in microsomes, lamellar bodies, and alveolar macrophages. (v) The incorporation of [14C]glycerol into phospholipids of lung slices increased. (vi) The activity of CTP:phosphocholine cytidylyltransferase bound to the microsomal fraction increased without any change in the activity of the soluble form of the enzyme in the lung. The results obtained when testosterone was administered to castrated rats were similar to those obtained in the control in all cases. These results suggest that the lipid concentration in the lung is regulated at least partly directly or indirectly by androgens.
Visual acuity and blood lipids in term infants fed human milk or formulae
Authors: Innis Sheila M. , Akrabawi Salim S. , Diersen‐Schade Deborah A. , Dobson M. Velma , Guy David G.
Published: November 2006

This multicenter, parallel group study determined plasma phospholipid and red blood cell (RBC) phosphatidylcholine and phosphatidylethanolamine fatty acids, plasma cholesterol, apo A‐1 and B, growth and visual acuity (using the acuity card procedure) in term infants fed from birth to 90 d of age with formula containing palm‐olein, high oleic sunflower, coconut and soy oil (22.2% 16∶0, 36.2% 18∶1, 18% 18∶2n−6, 1.9% 18∶3n−3) (n=59) or coconut and soy oil (10.3% 16∶0 18∶6% 18∶1, 34.2% 18∶2n−6, 4.7% 18∶3n−3) (n=57) or breast‐fed (n=56) with no formula supplementation. Different centers in North America were included to overcome potential bias due to differences in n−6 or n−3 fatty acids at birth or in breast‐fed infants that might occur in a single‐site study. Plasma and RBC phospholipid docosahexaenoic acid (DHA, 22∶6n−3) and arachidonic acid (AA, 20∶4n−6), cholesterol and apo B were significantly lower in the formula‐ than breast‐fed infants. There were no differences in looking acuity or growth among the breast‐fed and formula‐fed infants. No significant relations were found between DHA and looking acuity, or AA and growth within or among any of the infant groups. This study provides no evidence to suggest the formula provided inadequate n−6 or n−3 fatty acids for growth and looking acuity for the first 3 mon after birth.
Tandem mass spectrometric approach for determining structure of molecular species of aminophospholipids
Authors: Chen Su
Published: November 2006

Aminophospholipids, including glycerophosphatidylethanolamine, glycerophosphatidylserine and their Lyso analogous, have been analyzed by positive and negative ion liquid secondary ion ionization coupled to tandem mass spectrometry. The mass spectra of aminophospholipids obtained by tandem mass spectrometers with different configuration (liquid secondary ion‐electric‐magnetic sector coupled to quadrupole mass analyzer (low‐energy collision) or electricmagnetic sector (high‐energy collision), as well as electrospray ionization‐quadrupole mass analyzer combined with quadrupole mass analyzer (low‐energy collision), are compared. The mass spectra produced by low‐energy collisionally induced dissociation of the deprotonated molecules from aminophospholipids contain fragment ions for characterizing polar head moieties as well as fatty acid composition and position. The mass spectra generated by high‐energy collisionally induced dissociation of both protonated and deprotonated molecules from aminophospholipids show numerous product ions for identifying polar heads, composition, and location of fatty acid chains in molecular species. Triple quadrupole mass spectrometer with electrospray ionization exhibits remarkable superiority in detection sensitivity. Liquid secondary ion with electric‐magnetic sector coupled to quadrupole mass analyzer or electric‐magnetic sector instrument has the advantage of the capability of properly determining location of fatty acid chains in molecular species. This paper also describes an approach for structurally analyzing aminophospholipid species as 9‐fluorenylmethyloxy‐carbonyl derivatives by positive and negative ion liquid secondary ion mass spectrometry and high‐energy collisionally induced dissociation tandem mass spectrometry. It has been found that the derivatives of glycerophosphatidylethanolamine and glycerophosphatidylserine can readily be analyzed by the negative ion liquid secondary ion and tandem mass spectrometric methods.
Inhibition of pancreatic cancer growth by the dietary isoprenoids farnesol and geraniol
Authors: Burke Yvette D. , Stark M. Jennifer , Roach Steven L. , Sen Stephanie E. , Crowell Pamela L.
Published: November 2006

Fruits and vegetables have protective effects against many human cancers, including pancreatic cancer. Isoprenoids are one class of phytochemicals which have antitumor activity, but little is known about their effects on cancer of the pancreas. We tested the hypothesis that isoprenoids would inhibit the growth of pancreatic tumor cells. Significant (60–90%) inhibition of the anchorage‐independent growth of human MIA PaCa2 pancreatic tumor cells was attained with 25 μM farnesol, 25 μM geranylgeraniol, 100 μM perillyl amine, 100 μM geraniol, or 300 μM perillyl alcohol. We then tested the relative in vivo antitumor activities of dietary farnesol, geraniol, and perilyl alcohol against transplanted PC‐1 hamster pancreatic adenocarcinomas. Syrian Golden hamsters fed geraniol or farnesol at 20 g/kg diet exhibited complete inhibition of PC‐1 pancreatic tumor growth. Both farnesol and geraniol were more potent than perillyl alcohol, which inhibited tumor growth by 50% at 40 g/kg diet. Neither body weights nor plasma cholesterol levels of animals consuming isoprenoid diets were significantly different from those of pair‐fed controls. Thus, farnesol, geraniol, and perillyl alcohol suppress pancreatic tumor growth without significantly affecting blood cholesterol levels. These dietary isoprenoids warrant further investigation for pancreatic cancer prevention and treatment.
Effects of dietary cholesterol and triglycerides on lipid concentrations in liver, plasma, and bile
Authors: Booker Michael L. , LaMorte Wayne W. , Beer Eve R. , Hopkins Susan R.
Published: November 2006

Dietary cholesterol (CHL) and triglycerides (TG) can influence plasma, hepatic, and biliary lipid composition, but effects on lipids in these three compartments during the early stages of CHL gallstone formation have not been studied in parallel. We fed prairie dogs diets containing one of four tes oils (safflower, coconut, olive, or menhaden) at either 5 or 40% of calories, in the presence of 0 or 0.34% CHL, for 3 wk. In the absence of dietary CHL, increases in dietary TG produced 50–200% increases in the concentrations of biliary CHL and hepatic cholesteryl ester (CE), while the concentrations of hepatic free CHL (FC) as well as plasma FC and CE remained relatively unchanged. Increasing dietary CHL to 0.34% resulted in increases in hepatic FC of approximately 50% for all four fats regardless of whether they were supplied at 5 or 40% of calories. CHL supplementation caused more pronounced increases in biliary CHL (200–400%), hepatic CE (50–200%), plasma FC (up to 100%), and plasma CE (up to 150%), and these increases were exacerbated by concurrent supplementation of dietary fat and CHL (biliary CHL: 300–700%; hepatic CE: 100–250%; plasma FC: up to 165%; plasma CE: 100–350%). These results indicate that enhanced secretion of biliary CHL and, to a lesser extent, increased synthesis of hepatic CE, may be primary mechanisms for maintaining the hepatic FC pool. Furthermore, dietary CHL and high levels of fat intake are independent risk factors for increasing biliary CHL concentrations, and adverse effects on lipid concentrations in plasma and bile tend to be exacerbated by ingestion of diets rich in both fat and CHL.
The influence of dietary lipids on the composition and membrane fluidity of rat hepatocyte plasma membrane
Authors: Clamp A. G. , Ladha S. , Clark D. C. , Grimble R. F. , Lund E. K.
Published: November 2006

Weanling male Wistar rats were fed for five weeks on standard rat chow (23 g fat/kg diet) or one of four synthetic diets with butterfat, coconut oil, corn oil, or fish oil as the main lipid source (100 g fat/kg diet). In all diets, 10% of the fat was provided as corn oil to prevent essential fatty acid deficiency. Significant differences were observed in the saturated, monounsaturated, and polyunsaturated fatty acid composition, and in the ratio of cholesterol to phospholipid, in the hepatocyte membranes. The fluidity of hepatocyte plasma membranes was assessed using the fluorescence recovery after photobleaching technique and steady‐state fluorescence anisotropy of diphenylhexatriene. No significant differences were found in the fluidity of plasma membranes between animals on the different fat diets, despite diet‐induced changes in their fatty acid composition. However, the proportion of lipid free to diffuse in the plasma membrane varied with diet, being significantly greater (P<0.05) in animals fed chow (63.7%), coconut oil (61.5%), and butterfat (57.6%) diets than in those fed the corn oil (47.3%) diet. Animals fed fish oil showed an intermediate (50.0%) proportion of lipid free to diffuse. The data support the hypothesis that dietary lipids can change both the chemical composition and lateral organization (lipid domain structure) of rat hepatocyte plasma membranes.
Linear, steroidal, and triterpene esters, and steryl glycosides from Festuca argentina
Authors: Casabuono Adriana C. , Pomilio Alicia B.
Published: November 2006

Ester waxes and steryl glycosides of the grass Festuca argentina were studied. Saponification of the waxes from the petroleum ether extract led to n‐hexacosanol as the major single linear alcohol, along with pentacyclic triterpenols, such as β‐amyrin, germanicol, isobaurenol, lupeol, hopenol‐a and hopeol, and low amounts of sterols, such as cholesterol, campesterol, stigmasterol, sitosterol and dihydrositosterol, identified by gas chromatography/mass spectrometry (GC/MS). Fatty acids were identified as methyl esters as C12∶0, C14∶0, C16∶0, C18∶0, C18∶2, and C20∶0. The occurrence of a wide chainlength range of fatty acids and a single linear alcohol closely matched for other reports on the tribe Festuceae. On the contrary, pentacyclic triterpenols with a variety of skeletons, especially isobauerenol, are not usual as esters of fatty acids in the Gramineae. Low amounts of steryl glycosides were also obtained from the methylene chloride percolate of the methanol extract. Upon acetylation followed by hydrolysis, aglycones were identified by capillary gas‐liquid chromatography (GLC) and GC/MS. As Δ7‐cholesterol, campesterol, stigmasterol, sitosterol, dihydrositosterol, and the sugars as glucose, xylose, and arabinose by GLC of the respective alditol acetates. This is the first report on the linear, steryl, and triterpenyl esters of F. argentina. It is noteworthy that Δ7‐steryl glycosides are rare, and steryl monoarabinosides have not been proviously reported on the family Gramineae.
[3‐13C] γ‐linolenic acid: A new probe for 13C nuclear magnetic resonance studies of arachidonic acid synthesis in the suckling rat
Authors: Cunnane S. C. , Moine G. , Likhodii S. S. , Vogt J. , Corso T. N. , Brenna J. T. , Demmelmair H. , Koletzko B. , Tovar K. ‐H. , Kohn G. , Sawatzki G. , Muggli R.
Published: November 2006

Our objective was to develop a suitable probe to study metabolism of polyunsaturated fatty acids by 13C nuclear magnetic resonance (NMR) in the suckling rat pup. [3‐13C] γ‐Linolenic acid was chemically synthesized, and a 20 mg (Experiment 1) or 5 mg (Experiment 2) dose was injected into the stomachs of 6–10‐day‐old suckling rat pups that were then killed over a 192 h (8 d) time course. 13C NMR showed that 13C in γ‐linolenate peaked in liver total lipids by 12‐h post‐dosing and that [5‐13C]‐arachidonic acid peaked in both brain and liver total lipids 48–96 h post‐dosing. 13C enrichment in brain γ‐linolenic acid was not detected by NMR, but gas chromatography‐combustion‐isotope ratio mass spectrometry showed that its mass enrichment in brain phospholipids at 48–96 h post‐dosing was 1–2% of that in brain arachidonic acid. 13C was present in liver and brain cholesterol and in perchloric acid‐extractable water‐soluble metabolites in the brain, liver and carcass. We conclude that low but measurable amounts of exogenous γ‐linolenic acid do access the suckling rat brain in vivo. The slow time course of [5‐13C] arachidonic acid appearance in the brain suggests most of it was probably transported there after synthesis elsewhere, probably in the liver. Some carbon from γ‐linolenic acid is also incorporated into lipid products other than n−6 long‐chain polyunsaturated fatty acids.
An esterification protocol for cis‐parinaric acid‐determined lipid peroxidation in immune cells1,2
Authors: McGuire Susan O. , James‐Kracke Marilyn R. , Sun Grace Y. , Fritsche Kevin L.
Published: November 2006

Loss of fluorescence from cis‐parinaric acid (cPnA) is a sensitive indicator of lipid peroxidation. The purpose of this study was to utilize cPnA to determine, at the level of the intact immune cell, whether enrichment of membranes with polyunsaturated fatty acids (PUFA) increased lipid peroxidation. P388D1 macrophages were labeled by addition of cPnA as an ethanolic solution. Within two minutes of addition, in the absence of serum, cPnA rapidly intercalated into the plasma membrane. Lipid peroxidation was initiated by addition of Fe2+‐EDTA resulting in a dose‐dependent decrease in fluorescence with increased oxidant concentration. Cells previously enriched with PUFA and labeled by intercalation showed no differences in spontaneous or Fe2+‐induced lipid peroxidation. In separate experiments, 20 μM cPnA in ethanolic solution was injected into cell culture media containing 0.1% essentially fatty acid free bovine serum albumin (BSA). Cells were resuspended and incubated for 90 min at 37°C. After washing with BSA to remove cPnA which had not incorporated, 0.5% (0.1 μM) of the added cPnA was found esterified within cellular lipids. This level of cPnA provided a 100‐fold increase over basal autofluorescence levels. Cells labeled in this manner also lost fluorescence in a dose‐dependent manner as levels of oxidant stress increased. Cells enriched with PUFA and labeled by esterification had significantly increased rates and total amounts of lipid peroxidation. Co‐incubation with α‐tocopherol and PUFA resulted in a decrease in lipid peroxidation which was not significantly different from control cells. In conclusion, esterification of cPnA into membrane phospholipids can sensitively detect changes in lipid peroxidation induced by alteration of membrane PUFA and/or vitamin E content.
Novel oxylipins from the temperate red alga polyneura latissima: Evidence for an arachidonate 9(S)‐lipoxygenase
Authors: Jiang Zhi‐Dong , Gerwick William H.
Published: November 2006

The oxylipin chemistry of the temperate red alga Polyneura latissima has been investigated. The structures of three novel oxylipins, 8‐[1′(Z),3′(Z),6′(Z)‐dodecatriene‐1′‐oxyl‐5(Z),7(E)‐octadienoic acid, 7(S*)‐hydroxy‐8(S*),9(S*)‐epoxy‐5(Z), 11(Z),14(Z)‐eicosatrienoic acid, 7(R*)‐hydroxy‐8(S*), 9(S*)‐epoxy‐5(Z), 11(Z),14(Z)‐eicosatrienoic acid, together with two known eicosanoids, 9(S)‐hydroxy‐5(Z), 7(E), 11(Z), 14(Z)‐eicosatetraenoic acid, and 9, 15‐dihydroxy‐5(Z),7(E),11(Z),13(E)‐eicosatetraenoic acid, were elucidated by spectroscopic methods and chemical degradation. The oxygenation pattern of these oxylipins suggests that P. latissima metabolizes polyunsaturated fatty acids via a 9(S)‐lipoxygenase.
Photo‐initiated peroxidation of lipids in micelles by azaaromatics
Authors: Barclay L. R. C. , Crowe E. , Edwards C. D.
Published: November 2006

The monoazaaromatics, pyridine (1), hexyl nicotinate (2), and quinoline (3) and diazaaromatics pyrimidine (4) and purine (5), readily act as photo‐initiators for the peroxidation of methyl linoleate in 0.50 M SDS at 37°C giving free radical chain oxidations of linoleate. Quantitative kinetic runs on the order in substrate, RH, and in the rate of chain initiation, Ri, showed that the classical rate law for autoxidation,‐d[O2]/dt=(kp/(2 kt1/2))[RH]xRi1/2, is applicable to these photo‐initiated oxidations. The oxidizability of methyl linoleate under these conditions is 2.92×10−2 M−1/2 s−1/2. These peroxidations were inhibited by chromanol phenolic antioxidants of the vitamin E class, such as lipid‐soluble 2,2,5,7,8‐pentamethyl‐6‐hydroxychroman (PMHC) and water‐soluble 2‐carboxy‐2,5,7,8‐tetramethyl‐6‐hydroxychroman (Trolox) and derived rate constants for inhibition of peroxidation were kinh (PMHC)=4.35×104 M−1 s−1 and kinh (Trolox)=2.81×104 M−1 s−1 during inhibited oxidation of methyl linoleate photo‐initiated by 4. The products from photo‐initiated peroxidation of methyl linoleate by 1 through 5 were determined by reduction and high‐performance liquid chromatography analyses to be the 9‐and 13‐positional hydroperoxides of the four geometrical isomers: cis‐9, trans‐11 (6), trans‐10, cis‐12 (7), trans‐9, trans‐11 (8), and trans‐10, trans‐12 (9)‐octadecadienoates typical of the free radical chain mechanism of lipid peroxidation. Products from dye‐sensitized oxidation by Methylene Blue or Rose Bengal of methyl linoleate gave a product distribution of six hydroperoxides typical of oxidation by singlet oxygen. Thermal or photo‐initiated peroxidation of methyl linoleate in SDS gave some selectivity of oxidation at the 13‐position of the linoleate chain. The ratio of 13‐to 9‐oxidation varied in the range 1.23 to 1.14 as the cis/trans to trans/trans ratio of geometric isomers varied from 0.44 to 1.25 during photooxidation of increased amounts of linoleate in SDS. This selectivity is attributed to loss of the pseudo symmetry around the pentadienyl system in the lipid chain in the SDS system during the peroxidation.
Differentiation of human promyelocytic leukemia cell line HL60 by microbial extracellular glycolipids
Authors: Isoda Hiroko , Shinmoto Hiroshi , Kitamoto Dai , Matsumura Masatoshi , Nakahara Tadaatsu
Published: November 2006

Microbial extracellular glycolipids, succinoyl trehalose lipid (STL), and mannosylerythritol lipid (MEL) inhibited the growth of a human promyelocytic leukemia cell line, HL60, and induced their morphological changes. The results of specific and nonspecific leukocyte esterase activities showed that STL induced monocytotic differentiation while MEL induced granulocytic differentiation. STL and MEL markedly increased common differentiation‐associated characteristics in monocytes and granulocytes, such as nitroblue tetrazolium (NBT) reducing ability, expression of Fc receptors, and phagocytic activities in HL60 cells, respectively. Neither sugar moieties nor fatty acids in the free form, the individual components of STL and MEL, were effective at inducing the differentiation of HL60 cells. The induction of differentiation was not due to surface activities of STL and MEL on the basis of the complete ineffectiveness of the analogues tested. The composition of cell surface glycosphingolipids (GSL) changed such that the GM3/LacCer ratio increased in STL‐treated cells, whereas it decreased in MEL‐treated cells. HL60 cells treated with STL and MEL exhibited a significant decrease in the activity of the intracellular phospholipid‐ and Ca2+‐dependent protein kinase (protein kinase C). Furthermore, the serine/threonine phosphorylations in intact HL60 cells were clearly inhibited by the presence of GM3 and MEL, but not by LacCer and STL. These results suggest that the differentiation‐inducing activity of STL and MEL is not due to a simple detergent‐like effect but due to a specific action on the plasma membrane. The inhibitory effect of STL on protein kinase activity was through increasing GM3, but MEL had a direct inhibitory effect.
Altered phospholipid metabolism in sodium butyrate‐induced differentiation of C6 glioma cells
Authors: Sun Synthia H. , Ou Hsio‐Chung , Jang Te‐Hsuan , Lin Lian‐Bin , Huang Hsueh‐Meei
Published: November 2006

We examined the changes in phospholipid metabolisms in sodium butyrate‐treated C6 glioma cells. Treatment of 2.5 mM sodium butyrate for 24 h induced an increase in the activity of glutamine synthetase, suggesting that these cells were under differentiation. Similar treatment was associated with (i) increased arachidonic acid incorporation into phosphatidylcholine, and (ii) decreased arachidonic acid incorporation into phosphatidylinositol and (iii) phosphatidylethanolamine. These effects were subsequently investigated by examining the acylation process, de novo biosynthesis, and the agonist‐stimulated phosphoinositides hydrolysis in these cells. Our results indicated that sodium butyrate stimulated the acylation of arachidonic acid into lysophosphatidylcholine, lysophosphatidylethanolamine, and lysophosphatidylinositol. The glycerol incorporation into these lipids was not affected, but the inositol incorporation into these lipids was not affected, but the inositol incorporation into total chloroform extracts and Pl and phosphatidylinositol 4‐phosphate was decreased in the sodium butyrate‐treated cells. Moreover, the accumulation of the rapid histamine‐stimulated phosphoinositide metabolites, i.e., inositol monophosphate, inositol diphosphate, and inositol triphosphate (IP3) was decreased in these cells. To elucidate whether the decreased inositol phosphates were due to a decrease in the phosphoinositides hydrolysis, we measured the transient IP3 production directly by a receptor‐binding assay. Our results indicated that histamine‐stimulated transient IP3 formations were decreased. Taken together, these results indicated that multiple changes by multiple mechanisms of phospholipid metabolisms were found in sodium butyrate‐treated C6 glioma cells. The decreased IP3 formation and its subsequent action, i.e., Ca2+ mobilization, may play an early but pivotal role by which sodium butyrate induces C6 glioma cell differentiation.
Incorporation of long‐chain n‐3 fatty acids in tissues and enhanced bone marrow cellularity with docosahexaenoic acid feeding in post‐weanling Fischer 344 rats
Authors: Atkinson Trevor G. , Barker Heather J. , Meckling‐Gill Kelly A.
Published: November 2006

We wanted to examine the effects of an oil rich in docosahexaenoic acid (DHA), without eicosapentaenoic acid, on the composition of membrane phospholipid in a variety of tissues. Our in vitro studies had previously shown that DHA could modify glucose and nucleoside transport in cells in culture and also increase selectivity of the nucleoside drug, arabinosylcytosine (araC) toward tumor cells. Here we wanted to examine what effect DHA supplementation would have in the whole animal in terms of the chemosensitivity of normal bone marrow, the dose‐limiting tissue during chemotherapy, to araC. The purpose was to determine whether fatty acid supplementation might be useful as an adjuvant to chemotherapy. We fed diets containing 5% (w/w) low fat‐corn oil (LF‐CO group), 10% moderate fat‐safflower oil (MF‐SO group), or 10% DHASCOTM (MF‐DHA group) to weanling Fischer 344 rats for 8–9 wk. Feed intake and growth were not different between the different diets. Similarly, treatment of animals with the chemotherapeutic drug araC did not differentially affect growth, feed intake, or tissue fatty acid composition for the different diet groups. Fatty acid compositions of bone marrow, liver, red blood cells, plasma phospholipid and triglyceride, as well as skeletal and cardiac muscle, were substantially different between the dietary groups. The DHASCOTM oil contained 46% DHA (22:6n‐3) and resulted in profound incorporation of DHA in all tissues examined. The most dramatic response was seen in skeletal muscle of MF‐DHA fed animals where DHA represented 46% of membrane phospholipid fatty acids. This is likely to have consequences to muscle function. Although DHASCOTM contains a similar level of saturated fatty acids (42%), few differences in saturates were noted between the various dietary groups for most of the tissues examined. Both LF‐CO and MF‐SO diets were hypercholesterolemic, and the LF‐CO was also hypertriglyceridemic compared to the chow‐fed animals. Animals fed the MF‐DHA diet had the lowest triglyceride levels of any of the treatment groups and cholesterol levels comparable to chow‐fed animals. MF‐DHA had substantially higher numbers of colony‐forming units‐granulocyte macrophage (CFU‐GM) as reflected in a twofold higher bone marrow cellularity than either chow or LF‐CO animals, suggesting expansion of the bone marrow compartment with DHA feeding. Although higher than LF‐SO, the number of CFU‐GM in MF‐SO animals was not significantly higher than animals fed chow. Bone marrow from LF‐CO animals appeared to be more resistant to araC treatment than either MF group. Thus, DHA, fed as DHASCOTM, has advantages over low or moderate n‐6 diets and chow as it is has both hypolipidemic‐ and bone marrow‐enhancing properties in weanling Fischer 344 rats. This suggests that DHA supplementation may be useful in adjuvant chemotherapy.
Non‐insulin dependent diabetes mellitus in Psammomys obesus is independent of changes in tissue fatty acid composition
Authors: Collier G. R. , Collier F. McL , Sanigorski A. , Walder K. , Cameron‐Smith D. , Sinclair A. J.
Published: November 2006

Recently it has been postulated that membrane fatty acid composition may be involved in the pathogenesis of insulin resistance and non‐insulin dependent diabetes mellitus (NIDDM). The aim of this study was to determine whether alterations in tissue phospholipid (PL) fatty acids are present in hyperglycemic and hyperinsulinemic Psammomys obesus. On a native diet of salt bush, P. obesus (Israeli sand rat) remains lean and free of diabetes; however, when placed on a normal laboratory chow, a significant proportion of these animals develops a number of metabolic disorders associated with NIDDM, providing an ideal animal model of obesity and NIDDM. Four groups of mature P. obesus were studied: group A; normoglycemic and normoinsulinemic; group B: normoglycemic and hyperinsulinemic; group C: hyperglycemic and hyperinsulinemic; and group D: hyperglycemic hypoinsulinemic. In liver and red gastrocnemius muscle, there were no significant differences between groups, A, B, and in fatty acid composition of PL. Minor differences in individual fatty acids were demonstrated in group D animals (increased liver 20∶4n‐6 and increased muscle 22∶5n‐3); however, the unsaturation indices in liver and muscle were not significantly different between any of the groups. In considering that the minor changes in group D animals were not demonstrated in hyperinsulinemic group B animals or hyperglycemic, hyperinsulinemic group C animals, it is likely that the differences in group D animals were secondary to the more severe disturbances in glucose homeostasis and hypoinsulinemia present in these animals. The results of this study suggest that in this rodent diabetic model significant disturbances in glucose homeostasis and hyperinsulinemia may develop independently of changes in tissue fatty acid composition.
Phospholipid biosynthetic enzymes in human brain
Authors: Ross Brian M. , Moszczynska Anna , Blusztajn Jan K. , Sherwin Allan , Lozano Andres , Kish Stephen J.
Published: November 2006

Growing evidence suggests an involvement of brain membrane phospholipid metabolism in a variety of neurodegenerative and psychiatric conditions. This has prompted the use of drugs (e.g., CDPcholine) aimed at elevating the rate of neural membrane synthesis. However, no information is available regarding the human brain enzymes of phospholipid synthesis which these drugs affect. Thus, the objective of our study was to characterize the enzymes involved, in particular, whether differences existed in the relative affinity of substrates for the enzymes of phosphatidylethanolamine (PE) compared to those of phosphatidylcholine (PC) synthesis. The concentration of choline in rapidly frozen human brain biopsies ranged from 32–186 nmol/g tissue, a concentration similar to that determined previously for ethanolamine. Since human brain ethanolamine kinase possessed a much lower affinity for ethanolamine (Km=460 μM) than choline kinase did for choline (Km=17 μM), the activity of ethanolamine kinase in vivo may be more dependent on substrate availability than that of choline kinase. In addition, whereas ethanolamine kinase was inhibited by choline, and to a lesser extent by phosphocholine, choline kinase activity was unaffected by the presence of ethanolamine, or phosphoethanolamine, and only weakly inhibited by phosphocholine. Phosphoethanolamine cytidylyl‐transferase (PECT) and phosphocholine cytidylyltransferase (PCCT) also displayed dissimilar characteristics, with PECT and PCCT being located predominantly in the cytosolic and particulate fractions, respectively. Both PECT and PCCT exhibited a low affinity for CTP (Km approximately 1.2 mM), suggesting that the activities of these enzymes, and by implication, the rate of phospholipid synthesis, are highly dependent upon the cellular concentration of CTP. In conclusion, our data indicate different regulatory properties of PE and PC synthesis in human brain, and suggest that the rate of PE synthesis may be more dependent upon substrate (ethanolamine) availability than that of PC synthesis.