bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of myocardial lipoprotein lipase by U‐57,908 (RHC 80267)
Authors: Carroll Rogayah , Severson David L.
Published: November 2006

U‐57,908 (RHC 80267) was shown to inhibit lipoprotein lipase (LPL) activity in cardiac myocytes from rat hearts; the concentrations required for inhibition to 50% of control activity were 1.1 μM and 2.5 μM for myocyte homogenates and a post‐heparin medium preparation, respectively. The inhibition of LPL activity by U‐57,908 was not changed when the concentration of the triolein substrate and apolipoprotein CII activator in the assay was reduced. The availability of U‐57,908 as a potent and selective LPL inhibitor may provide a useful experimental approach in studies on lipoprotein metabolism.
Glycolipids of a human glioma cell line bearing receptors for platelet‐derived growth factor (PDGF)
Authors: Yates Allan J. , Agudelo Javier D. , Sung Ching‐Ching
Published: November 2006

Glycolipids of U‐1242 MG were characterized because results of previous studies showed that exogenous gangliosides, especially GM3, inhibit PDGF‐stimulated growth of this human glioma cell line. GM3 and GM2 are the major gangliosides; both separate as doublets with thin‐layer chromatography. The major neutral glycolipid is glucocerebroside with nonhydroxy fatty acids, but paragloboside, ceramide dihexoside, globoside, and asialoGM2 (GA2) are also present. The coexistence in U‐1242 MG of these gangliosides and the PDGF receptor, whose mitogenic signal is modulated by GM3 in these cells, suggests a possible functional relationship among them with respect to growth regulation.
Liver lipid profiles of adults taking therapeutic doses of aspirin
Authors: Rabinowitz Joseph L. , Baker Daniel G. , Villanueva Thelma G. , Asanza Aurora P. , Capuzzi David M.
Published: November 2006

The distributions of lipids of hepatic specimens obtained at autopsy from 7 adult patients who had been taking large amounts of aspirin for arthritis were compared to 7 control samples obtained from livers of autopsied adults without prior liver disease. The total neutral lipid levels of control livers were approximately one‐third lower than those observed for livers of patients on aspirin. In addition, the phospholipid content of control specimens was significantly greater than that of livers from adult patients that had been on a high dose of aspirin for a long time. Examination of individual lipid classes showed that the concentrations of free fatty acids, triacylglycerols, and mono‐ and diacylglycerols were highest in livers of patients with aspirin exposure, and that all phospholipids were diminished. Phosphatidylcholines and phosphatidylethanolamines showed the greatest decrease. These results suggest that the livers of patients taking large amounts of aspirin may accumulate fatty acids and neutral lipids due to an impairment in the oxidation of fatty acids by hepatocytes. The data obtained also suggest that needle biopsy of the liver with measurement of distribution of hepatic lipids, perhaps together with histopathologic examination, may provide useful diagnostic information.
Effect of fish oil supplementation on the excretion of the major metabolite of prostaglandin E in healthy male subjects
Authors: Ferretti Aldo , Judd Joseph T. , Ballard‐Barbash Rachel , Nair Padmanabhan P. , Taylor Philip R. , Clevidence Beverly A.
Published: November 2006

We investigated the effect of fish oil supplementation on the synthesis of prostaglandin E (PGE)in vivo by measuring the excretion of its catabolite, PGE‐M, in 24‐hr urine by gas chromatography/mass spectrometry. Forty healthy male volunteers (24–57 years of age) consumed a controlled basal diet providing 40% of energy from fat (P/S ratio about 0.8∶1), 130 mg/1000 kcal cholesterol, and a minimum of 22 mg/day of α‐tocopherol (α‐T), for three experimental periods lasting a total of 28 weeks. During period 1 (10 weeks) the diet was supplemented with placebo (PO) capsules (15×1 g/day) consisting of a blend of fats approaching the fatty acid profile of the basal diet. This was followed by a second 10‐week period during which the subjects received 15×1 g/day capsules of fish oil concentrate (FOC). During period 3 (8 weeks) they continued the 15 g/day intake of FOC but received an additional 200 mg/day of α‐T. PO and FOC capsules contained 1 mg α‐T/g fat as antioxidant. A 14% reduction of PGE‐M excretion was observed after 10 weeks of FOC supplementation (period 2), compared to an identical period of placebo supplementation (period 1), P=0.009. PGE‐M excretion during the last week of period 3 was not significantly different from that at the end of period 2. The reduction in PGE synthesis in response to the relatively high marine oil supplementation was large in many subjects participating in this study.
Sesamin is a potent and specific inhibitor of Δ5 desaturase in polyunsaturated fatty acid biosynthesis
Authors: Shimizu Sakayu , Akimoto Kengo , Shinmen Yoshifumi , Kawashima Hiroshi , Sugano Michihiro , Yamada Hideaki
Published: November 2006

Incubation with sesame oil increases the mycelial dihomo‐γ‐linolenic acid content of an arachidonic acid‐producing fungus,Mortierella alpina, but decreases its arachidonic acid content [Shimizu, S., K. Akimoto, H. Kawashima, Y. Shinmen and H. Yamada (1989)J. Am. Oil Chem. Soc. 66, 237–241]. The factor causing these effects was isolated and identified to be (+)‐sesamin. The results obtained in experiments with both a cell‐free extract of the fungus and with rat liver microsomes demonstrated that (+)‐sesamin specifically inhibits Δ5 desaturase at low concentrations, but does not inhibit Δ6, Δ9 and Δ12 desaturases. Kinetic analysis showed that (+)‐sesamin is a noncompetitive inhibitor (Ki for rat liver Δ5 desaturase, 155 μM). (+)‐Sesamolin, (+)‐sesaminol and (+)‐episesamin, also inhibited only Δ5 desaturases of the fungus and liver. These results demonstrate that (+)‐sesamin and related lignan compounds present in sesame seeds or its oil are specific inhibitors of Δ5 desaturase in polyunsaturated fatty acid biosynthesis in both microorganisms and animals.
Acylation of lyso platelet‐activating factor by splenocytes of the rainbow trout,Oncorhyncus mykiss
Authors: Pool G. L. , Samples B. , Turner M. R. , Lumb R. H.
Published: November 2006

In mammalian systems, platelet‐activating factor, 1‐O‐alkyl‐2‐acetyl‐sn‐glycero‐3‐phosphocholine, (PAF) is rapidly inactivated by a deacetylation/reacylation system that produces 1‐O‐alkyl‐2‐acyl‐sn‐glycero‐3‐phosphocholine which is highly enriched in arachidonic acid. There is some evidence that n−3 fatty acids may have an impact on this system in humans but the nature of this impact is unclear. In rainbow trout, n−3 fatty acids are known to be essential dietary components which are derived through the food chain. Substantial quantities of n−3 fatty acids are found in trout membrane phospholipids. We show here that in sharp contrast to mammalian cells, trout cells acylate lyso platelet‐activating factor, alkyl‐GPC, 1‐O‐alkyl‐2‐lyso‐sn‐glycero‐3‐phosphocholine, (lyso‐PAF) with a high degree of specificity for n−3 fatty acids. When [3H]lysoPAF was incubated with these cells, only three molecular species of alkylacylglycerophosphocholine were produced, and 92% contained n−3 fatty acids. Since isolated membranes yielded similar results, it appears that the acylation proceedsvia a coenzyme A‐independent transacylase as found in mammalian systems.
Differential effects of ursodeoxycholic acid and ursocholic acid on the formation of biliary cholesterol crystals in mice
Authors: Uchida Klyohisa , Aklyoshi Takashi , Igimi Hirotsune , Takase Haruto , Nomura Yasuharu , Ishihara Shouichi
Published: November 2006

The preventive effect of 3α,7β,12α‐trihydroxy‐5β‐cholanoic acid (ursocholic acid) and ursodeoxycholic acid on the formation of biliary cholesterol crystals was studied in mice. Cholesterol crystals developed with 80% incidence after feeding for five weeks a lithogenic diet containing 0.5% cholesterol and 0.25% sodium cholate. When 0.25% ursocholic acid or ursodeoxycholic acid was added to the lithogenic diet, the incidence as well as the grade (severity) of the gallstones were reduced. Plasma and liver cholesterol levels were decreased by ursodeoxycholic acid but not by ursocholic acid. Gallbladder cholesterol and phospholipid levels were decreased by both bile acids. The biliary bile acid level was decreased by ursocholic acid but not by ursodeoxycholic acid. After feeding ursocholic acid, its level in the bile was about 25% and the levels of cholic acid and β‐muricholic acid decreased. Fecal sterol excretion was not changed by ursocholic acid, but was increased by ursodeoxycholic acid. After feeding ursocholic acid, fecal excretion of deoxycholic acid, cholic acid, and ursocholic acid increased. No differences were found between mice, with or without gallstones, in plasma and liver cholesterol levels, biliary phospholipid and bile acid levels, fecal sterol and bile acid levels, and biliary and fecal bile acid composition. The results suggest that the lower incidence of crystal formation after treatment with ursocholic acid is probably by a different mechanism than with ursodeoxycholic acid. In the mouse model, ursodeoxycholic acid exerts its effect at least partially, by decreasing cholesterol absorption. Ursocholic acid is well absorbed and excreted into bile and transformed into deoxycholic acid by the intestinal microflora in mice.
Phospholipid requirement of progesterone 5α‐reductase from gastric mucosa microsomes of guinea pig
Authors: Ichihara Kosuke , Tanaka Chikage
Published: November 2006

Progesterone 5α‐reductase partially purified from gastric mucosa microsomes was stimulated by short‐chain synthetic phosphatidylcholines (PC), such as dilauroyl PC, but not by various PC from biological sources. Phosphatidylserine (PS) activated the gastric 5α‐reductase to a limited extent compared to the liver 5α‐reductase described previously [Ichihara, K., and Tanaka, C. (1987)Biochem. Biophys. Res. Commun. 149, 482–487]. In search of more effective phospholipid activators, we tested the effects of various lysophospholipids on 5α‐reductase activity. Strongly stimulatory effects were observed when lysophosphatidylcholine (lysoPC) and lysophosphatidylethanolamine (lysoPE) were used instead of PC and phosphatidylethanolamine. Examination of synthetic lysoPC and lysoPE differing in acyl chain lengths showed that fatty chains of 12 to 16 carbons were effective in stimulating the 5α‐reductase. By contrast, other lysophospholipids such as lysophosphatidic acid, lysophosphatidylglycerol or lysophosphatidylserine (lysoPS) greatly inhibited 5α‐reductase activity. These findings suggest that gastric 5α‐reductase may be under dual regulation; lysoPC and lysoPE may play important roles as positive effectors, whereas lysophosphatidic acid, lysophosphatidylglycerol and lysoPS act as negative effectors in progesterone 5α‐reductase regulation.
Evidence of extensive phospholipid fatty acid methylation during the assumed selective methylation of plasma free fatty acids by diazomethane
Authors: Lin Chu , Blank Edward W. , Ceriani Roberto L. , Baker Nome
Published: November 2006

We compared a conventional method (Method I) for measuring plasma free fatty acid (FFA) concentrations with two more rapid procedures (Method II and Method III). Method I required total lipid extraction, separation of FFA by thin‐layer chromatography, methylation, and gas‐liquid chromatographic analysis of the fatty acid (FA) methyl esters. Method II was a colorimetric procedure. Method III relied upon diazomethane's presumed ability to selectively methylate FFA even in the presence of FA esters. The three methods were compared using plasma from fasted and from fed nude mice, tumor‐bearing mice (MX‐1 and ZR‐75‐1 human mammary carcinomas), and controls. Method II, was less reliable than Method I, but both gave similar mean values for plasma FFA levels in fasted mice. Both Methods I and II also showed similar lowering of plasma FFA levels after feeding previously fasted mice. Method III consistently gave values that were far greater than those obtained using Methods I and II. Moreover, highly significant differences between fasted and fed mice were obscured by direct methylation of plasma FFA with diazomethane (Method III). The excess FA methyl esters formed in Method III were derived from plasma phospholipids, but not from plasma triacylglycerols. After feeding fasted mice, plasma free palmitic acid and oleic acid levels fell (Method I); by contrast, the excess “FFA” formed by methylation of plasma phospholipid FA increased two‐fold and fourteen‐fold, respectively. Caution is therefore advised in the use of direct methylating agents when measuring total and individual plasma FFA levels.
Maternal protein deficiency in rat: Effects on central nervous system gangliosides and their catabolizing enzymes in the offspring
Authors: Prasad V. V. T. S.
Published: November 2006

Maternal protein deficiency imposed on rats a month prior to conception, and during gestation and lactation, resulted in a significant cell loss in cerebrum, cerebellum, brain stem and spinal cord of pups at weaning. The cerebellum was the most affected central nervous system (CNS) region; it contained only 25% of the normal cell number. Undernourished pups were also found to have a lower concentration of total gangliosides in cerebrum as compared to that of controls. However, the total ganglioside concentration was unaffected in the cerebellum, brain stem and spinal cord by maternal undernutrition. In all regions, undernutrition caused significant changes in the proportions of individual gangliosides; these alterations were region‐specific. Sialidase, β‐galactosidase, β‐glucosidase, and β‐hexosaminidase, which are involved in the catabolism of gangliosides, showed higher activities in all the regions of undernourished pups, suggesting that these enzymes may play a role in maintaining the porportions of various ganglioside fractions.
Supplementation with evening primrose oil in atopic dermatitis: Effect on fatty acids in neutrophils and epidermis
Authors: Schäfer Liselotte , Kragballe Knud
Published: November 2006

We investigated the effect of oral supplementation with evening primrose oil, containing 72% linoleic acid (18∶2n−6) and 10% γ‐linolenic acid (18∶3n−6), on the epidermal and neutrophil phospholipid fatty acid composition in 15 patients with atopic dermatitis (AD). Three different dose levels, 4, 8 and 12 capsules per day containing 0.5 g oil, were given to three groups of patients. The only n−6 fatty acid showing a significant (p<0.05) dose‐related increase was dihomo‐γ‐linolenic acid (20∶3n−6) in neutrophil phospholipids. The highest dose increased dihomo‐γ‐linolenic acid by 45% in neutrophil phospholipids, by 46% in lesion‐free epidermal phosphatidylcholine, and by 15% in lesion‐free epidermal phosphatidylethanolamine. In both lesional and lesion‐free epidermis, supplementation resulted in a rise in the ratio between n−6 and monounsaturated fatty acids, reaching significance (p<0.05) in lesional epidermis. This study shows that moderate and favorable fatty acid changes can be obtained in the epidermis of AD patients, when given 6 g per day of oil rich in n−6 fatty acids. The abnormal lipid and fatty acid pattern of the atopic epidermis may be involved in the pathogenesis of the disease, and should therefore be the target for future therapeutic approaches with fatty acid supplements.
Purification and characterization of a cytochrome P450 isozyme catalyzing lanosterol 14α‐demethylation (P45014DM) in hamster liver
Authors: Sekigawa Yoshio , Fukuhara Morio , Sonoda Yoshiko , Sato Yoshihiro
Published: November 2006

To characterize cholesterol synthesis in Syrian golden hamster, an isozyme of cytochrome P450, lanosterol 14α‐demethylase (P45014DM), which catalyzes the initial step in the biosynthesis of cholesterol from lanosterol, was purified and its mode of induction by microsomal enzyme inducers was characterized. P450450DM was purified from hamster livers by chromatography using aminooctyl‐Sepharose CL‐4B, hydroxylapatite, DEAE‐5PW, and CM‐Sephrose CL‐6B columns, to a specific content of 12.8 nmol/mg‐protein. The purified protein displayed a single band on SDS‐polyacrylamide gel electrophoresis with an apparent molecular weight of 52,000. The absorption spectra of the oxidized form of the purified protein howed a Soret peak at 417 nm in a low‐spin state and a Soret peak of reduced CO‐binding complex at 448 nm. In a reconstituted system, the purified protein catalyzed 14α‐demethylation of 24,25‐dihydrolanosterol (1.58 nmol/min/nmol‐P450), although it did not show any activities toward testosterone and 7‐ethoxyresorufin, marker substrates of other P450 families. Immunoblot analysis using an antibody against porcine P45014DM, which inhibited the activity of lanosterol 14α‐demethylation in the hamster liver microsomes, demonstrated that the level of this isozyme protein was markedly decreased in dexamethasone‐treated hamster livers. This was accompanied by a decrease in the enzyme activity. In contrast, the levels and the activity in the phenobarbital‐and 3‐methylcholanthrene‐treated hamsters were almost equal to that in the untreated animals.
Effect of tocotrienols on the growth of a human breast cancer cell line in culture
Authors: Nesaretnam Kalanithi , Guthrie Najla , Chambers Ann F. , Carroll Kenneth K.
Published: November 2006

The tocotrienol‐rich fraction (TRF) of palm oil consists of tocotrienols and some α‐tocopherol (α‐T). Tocotrienols are a form of vitamin E having an unsaturated side‐chain, rather than the saturated side‐chain of the more common tocopherols. Because palm oil has been shown not to promote chemically‐induced mammary carcinogenesis, we tested effects of TRF and α‐T on the proliferation, growth, and plating efficiency (PE) of MDA‐MB‐435 estrogen‐receptor‐negative human breast cancer cells. TRF inhibited the proliferation of these cells with a concentration required to inhibit cell proliferation by 50% of 180 μg/mL, whereas α‐T had no effect at concentrations up to 1000 μg/mL as measured by incorporation of [3H]thymidine. The effects of TRF and α‐T also were tested in longer‐term growth experiments, using concentrations of 180 and 500 μg/mL. We found that TRF inhibited the growth of these cells by 50%, whereas α‐T did not. Their effect on the ability of these cells to form colonies also was studied, and it was found that TRF inhibited PE, whereas α‐T had no effect. These results suggest that the inhibition is due to the presence of tocotrienols in TRF rather than α‐T.
Oxidative susceptibility of low density lipoprotein from rabbits fed atherogenic diets containing coconut, palm, or soybean oils
Authors: Yap S. C. , Choo Y. M. , Hew N. F. , Yap S. F. , Khor H. T. , Ong A. S. H. , Goh S. H.
Published: November 2006

The oxidative susceptibilities of low density lipoproteins (LDL) isolated from rabbits fed high‐fat atherogenic diets containing coconut, palm, or soybean oils were investigated. New Zealand white rabbits were fed atherogenic semisynthetic diets containing 0.5% cholesterol and either (i) 13% coconut oil and 2% corn oil (CNO), (ii) 15% refined, bleached, and deodorized palm olein (RBDPO), (iii) 15% crude palm olein (CPO), (iv) 15% soybean oil (SO), or (v) 15% refined, bleached, and deodorized palm olein without cholesterol supplementation [RBDPO(wc)], for a period of twelve weeks. Total fatty acid compositions of the plasma and LDL were found to be modulated (but not too drastically) by the nature of the dietary fats. Cholesterol supplementation significantly increased the plasma level of vitamin E and effectively altered the plasma composition of long‐chain fatty acids in favor of increasing oleic acid. Oxidative susceptibilities of LDL samples were determined by Cu2+‐catalyzed oxidation which provide the lag times and lag‐phase slopes. The plasma LDL from all palm oil diets [RBDPO, CPO, and RBDPO(wc)] were shown to be equally resistant to the oxidation, and the LDL from SO‐fed rabbits were most susceptible, followed by the LDL from the CNO‐fed rabbits. These results reflect a relationship between the oxidative susceptibility of LDL due to a combination of the levels of polyun‐saturated fatty acids and vitamin E.
Dietary lipid modification of myocardial eicosanoids following ischemia and reperfusion in the rat
Authors: Abeywardena Mahinda Y. , Charnock John S.
Published: November 2006

Several different edible oils were compared for their ability to modify eicosanoid biosynthesis following experimentally‐induced myocardial ischemia and reperfusion in the rat. Two types of palm oil [neutralized, bleached, and deodorized (NBDPO) and refined, bleached, and deodorized (RBDPO)] and partially hydrogenated soybean oil (SBO) were tested against a diet supplemented with sunflower seed oil (SSO) rich in n−6 polyunsaturated fatty acids (PUFA). Fish oil (FO) rich in n−3 PUFA, with its known cardioprotective actions, served as an internal reference point for the study. Test oils were fed as a 12% (w/w) supplement for nine months before the induction of myocardial ischemia and reperfusion. Palm oil diets exerted effects indistinguishable from the SBO group against cardiac arrhythmia, which occurred following alterations to coronary blood flow. Arrhythmic potentials, as expressed by a hierarchical scale (0–9) of arrhythmia score, were: SSO, 1.5±0.5; FO, 0.9±0.4; SBO; 3.1±0.5*; NBDPO, 3.2±0.5*; RBDPO, 3.3±0.6*,*P<0.05 vs. SSO. Following ischemia and reperfusion, both SSO and RBDPO groups tended to show an increase in myocardial prostacyclin, with the effect being more prominent in the RBDPO group (SSO, 10%; RBDPO, 25%). Thromboxane production was reduced in the FO group. Interestingly, cardiac muscle from both FO and palm oil groups displayed a reduced capacity to produce 12‐hydroxyeicosatetraenoic acid SSO, 591.9±95.8; SBO, 375.5±48.9; NBDPO, 287.2±64.7*; RBDPO, 230.9±80.2**; FO, 203.7±81.4** (ng/g dry wt,*P<0.05,**P<0.01). No clear relationship was seen between the availability of 20∶4n−6 in myocardial phospholipids and eicosanoid profile. Data suggests that fatty acid composition of edible oils is not the only determinant of arrhythmic vulnerability and eicosanoid production.
Plasma lipids are affected similarly by dietary lauric or palmitic acid in gerbils and monkeys
Authors: Pronczuk Andrzej , Khosla Pramod , Hajri Tahar , Hayes K. C.
Published: November 2006

To compare the relative impact of dietary lauric acid (12∶0) and palmitic acid (16∶0) on plasma lipids, two fat‐sensitive species, Mongolian gerbils and cebus monkeys, were fed cholesterol‐free, purified diets enriched with either 12∶0‐rich or 16∶0‐rich fats, while all other fatty acids were held constant by selective blending of up to five natural fats or oils. The two gerbil diets (40 en% from fat) allowed for an 8 en% exchange between 12∶0 and 16∶0, and the monkey diets (31 en% from fat) allowed for 6 en% exchange beteen these two fatty acids. Eight gerbils received the diets for eight weeks, and 12 cebus monkeys were fed each diet in a cross‐over design for up to 22 wk. Both diets resulted in similar plasma cholesterol, triglyceride, and high density lipoprotein cholesterol concentrations within each species. Additionally, separation of cebus lipoproteins by discontinuous density‐gradient ultracentrifugation failed to show any dietary differences in concentration or composition of the three major lipoprotein classes (d<1.019, 1.019–1.055, and 1.055–1.168 g/mL). Thus, in two species sensitive to manipulations in dietary fat while consuming cholesterol‐free diets, 16∶0 was not hypercholesterolemic relative to 12∶0.
Response of hypercholesterolemic subjects to administration of tocotrienols
Authors: Qureshi A. A. , Bradlow B. A. , Brace L. , Manganello J. , Peterson D. M. , Pearce B. C. , Wright J. J. K. , Gapor A. , Elson C. E.
Published: November 2006

The cholesterol‐suppressive actions of Palmvitee and γ‐tocotrienol were assessed in hypercholesterolemic subjects after acclimation to the American Heart Association Step 1 dietary regimen for four and eight weeks, respectively. The four‐week dietary regimen alone elicited a 5% decrease (P<0.05) in the cholesterol level of the 36 subjects. Subjects continuing on the dietary regimen for a second four‐week period experienced an additional 2% decrease in their cholesterol levels. Dietary assessments based on unanticipated recalls of 24‐h food intake records suggest that significant reductions in energy and fat, predominantly in saturated fat, intakes are responsible. The subjects experienced significant Palmvitee‐ and γ‐tocotrienol‐mediated decreases in cholesterol. The group of subjects acclimated to the dietary regimen for four weeks responded to Palmvitee (a blend of tocols providing 40 mg α‐tocopherol, 48 mg α‐tocotrienol, 112 mg γ‐tocotrienol, and 60 mg δ‐tocotrienol/day for four weeks) with a 10% decrease in cholesterol (P<0.05). Dietary assessments showed no further change in energy and fat intakes. α‐Tocopherol attenuates the cholesterol‐suppressive action of the tocotrienols. The second group of subjects, acclimated to the dietary regimen for eight weeks, received 200 mg‐γ‐tocotrienol/d for four weeks. The cholesterol‐suppressive potency of this α‐tocopherol‐free preparation was calculated to be equivalent to that of the mixture of tocotrienols (220 mg) used in the prior study. Cholesterol levels of the 16 subjects in the second group decreased 13% (P<0.05) during the four‐week trial. Plasma apolipoprotein B andex vivo generation of thromboxane B2 were similarly responsive to the tocotrienol preparations, whereas neither preparation had an impact on high density lipoprotein cholesterol and apolipoprotein A‐I levels.
Antioxidant effects of tocotrienols in patients with hyperlipidemia and carotid stenosis
Authors: Tomeo A. C. , Geller M. , Watkins T. R. , Gapor A. , Bierenbaum M. L.
Published: November 2006

Antioxidants may have a role in the prevention of atherosclerosis. In the present trial, we investigated the antioxidant properties of Palm Vitee, a γ‐tocotrienol‐, and α‐tocopherol enriched fraction of palm oil, in patients with carotid atherosclerosis. Serum lipids, fatty acid peroxides, platelet aggregation, and carotid artery stenosis were measured over an 18‐month period in fifty patients with cerebrovascular disease. Change in stenosis was measured with duplex ultrasonography. Ultrasound scans were done at six months, twelve months, and yearly thereafter. Bilateral duplex ultrasonography revealed apparent carotid atherosclerotic regression in seven and progression in two of the 25 tocotrienol patients, while none of the control group exhibited regression and ten of 25 showed progression (P<0.002). Serum thiobarbituric acid reactive substances, anex vivo indicator of maximal platelet peroxidation, decreased in the treatment group from 1.08±0.70 to 0.80±0.55 μM/L (P<0.05) after 12 mon, and in the placebo group, they increased nonsignificantly from 0.99±0.80 to 1.26±0.54 μM/L. Both tocotrienol and placebo groups displayed significantly attenuated collagen‐induced platelet aggregation responses (P<0.05) as compared with entry values. Serum total cholesterol, low density lipoprotein cholesterol, and triglyceride values remained unchanged in both groups, as did the plasma high density lipoprotein cholesterol values. These findings suggest that antioxidants, such as tocotrienols, may influence the course of carotid atherosclerosis.
Distribution of cholesterol among its carriers in the bile of male and female hamsters
Authors: Mikami Takahiro , Cohen Bertram I. , Mikami Yasuko , Ayyad Nariman , Mosbach Erwin H.
Published: November 2006

The distribution of cholesterol among its carriers was studied in the bile of male and female hamsters. Sasco hamsters (Sasco Inc., Omaha, NE) were fed a semipurified diet with 0.0% cholesterol and 4% butterfat (group 1, males; group 4, females); a semipurified diet with 0.3% cholesterol and 1.2% plamitic acid (group 2, males; group 5, females); and a semipirified diet with 0.3% cholesterol and 4% safflower oil (group 3, males; group 6, females). At the end of six weeks, gallstones were found only in male hamsters receiving both cholesterol and dietary fat (fatty acid) (incidence of cholesterol stones: 90% in group 2; 22% in group 3). The biliary cholesterol carriers were separated and isolated from the bile of the hamsters by gel filtration chromatography, using the method of Pattinson [Pattinson, N.R., Willis, K.E., and Frampton, C.M. (1991)J. Lipid Res. 32, 205–214]. In those male hamsters that formed cholesterol gallstones, significant amounts of cholesterol were present in the void volume which contained large cholesterol phospholipid vesicles (void volume vesicles) (23% in group 2 and 15% in group 3). Smaller cholesterol/phospholipid vesicles were eluted next (fractions 30–45) and contained 15% of biliary cholesterol in group 2 and 21% in group 3. The remainder of the cholesterol was associated with mixed cholesterol/phospholipid/bile salt micelles. The cholesterol/phospholipid ratio was larger in both the void volume vesicles and small vesicles (2.40 and 1.48 in group 2; 2.56 and 1.33 in group 3, respectively) compared to the micelles (about 0.3 in groups 2 and 3). In contrast, the bile of the female hasmters contained few vesicles (3% small vesciles in group 5) and the cholesterol/phospholipid ratio of these vesicles was lower (0.94). Hamsters fed cholesterol‐free diets (groups 1 and 4) had no biliary cholesterol/phospholipid vesilces; and cholesterol was present in micelles. The results suggest that both the gender and the diet of the hamsters affected the distribution of biliary cholesterol between vesicles and micelles. The development of cholelithiasis in this animal model appears to depend on the rapid nucleation of cholesterol‐rich phospholipid vesicles in bile.
Evidence that palmitic acid is absorbed assn‐2 monoacylglycerol from human milk by breast‐fed infants
Authors: Innis Sheila M. , Dyer Roger , Nelson Carolanne M.
Published: November 2006

Milk fatty acids consist of about 20–25% palmitic acid (16∶0), with about 70% of 16∶0 esterified to thesn‐2 position of the milk triacylglycerols. Hydrolysis of dietary triacylglycerols by endogenous lipases producessn‐2 monoacylglycerols and free fatty acids, which are absorbed, reesterified, and then secreted into plasma. Unesterified 16∶0 is not well absorbed and readily forms soaps with calcium in the intestine. The positioning of 16∶0 at thesn‐2 position of milk triacylglycerols could explain the high coefficient of absorption of milk fat. However, the milk lipase, bile salt‐stimulated lipase, has been suggested to complete the hydrolysis of milk fat to free fatty acids and glycerol. These studies determined whether 16∶0 is absorbed from human milk assn‐2 monopalmitin by comparison of the plasma triacylglycerol total andsn‐2 position fatty acid composition between breast‐fed and formula‐fed term gestation infants. The human milk and formula had 21.0 and 22.3% of 16∶0, respectively, with 54.2 and 4.8% 16∶0 in the fatty acids esterified to the 2 position. The plasma triacylglycerol total fatty acids had 26.0±0.6 and 26.2±0.6% of 16∶0, and thesn‐2 position fatty acids had 23.3±3.3 and 7.4±0.7% of 16∶0 in the three‐month‐old exclusively breast‐fed (n=17) and formula‐fed (n=18) infants, respectively. Marked differences were found in the plasma total and the 2 position phospholipid percentage of 20∶4ω6, i.e., 11.6±0.3 and 6.9±0.6 (total), 17.7±1.4 and 9.7±0.6 (sn‐2 position) and percentage of 22∶6ω3, 4.6±0.3 and 2.1±0.3 (total), 5.6±0.6 and 2.0±0.2 (sn‐2 position) for the breast‐fed and formula‐fed infants, respectively. These studies provide convincing evidence that 16∶0 is absorbed from human milk assn‐2 monoacyl‐glycerol. The metabolic significance of the differences in positional distribution of fatty acids in the plasma lipids of breast‐fed and formula‐fed infants is not known.
In vitro activation of mouse skin protein kinase C by fatty acids and their hydroxylated metabolites
Authors: Lo Herng‐Hsiang , Bartek Gwendolyn A. , Fischer Susan M.
Published: November 2006

To understand how dietary fatty acids differentially modulate mouse skin tumorigenesis, the ability of specific fatty acids and their derivatives to activate murine epidermal protein kinase C (PKC)in vitro was investigated. Total PKC from untreated female SSIN mouse skin was partially purified and incubated with specific fatty acids at concentrations up to 300 μM in the presence of Ca2+ and phosphatidylserine. Thecis‐unsaturated fatty acids tested, ranging from 16∶1 to 22∶6, stimulated PKC activity in a similar dose‐dependent manner with an approximate threefold maximum increase over control. Neither the number ofcis‐double bonds nor the chainlength of these fatty acids affected their relative ability to activate PKC.trans‐Fatty acids, with the exception of linoelaidic acid (t,t‐18∶2n−6), exhibited about half of the potency of their correspondingcis‐isomers in stimulating PKC at the plateau concentration (200 μM) or lower. Substitutions close to the double bond oncis‐fatty acids abolished their ability to activate PKC. The hydroxylated metabolites of arachidonic acid (20∶4n−6) and linoleic acid (c,c‐18∶2n−6), i.e., the hydroxyeicosatetraenoic acids (HETE) and hydroxyoctadecadienoic acids (HODE), also activated mouse skin PKCin vitro, but only about half as effectively as did the respective parent fatty acids. The results suggest that both hydroxyl substitution andtrans‐configuration of HETE and HODE are responsible for their reduced ability to activate PKC. Overall the data suggests that the reduced skin tumor yield observed in mice fed diets high inc,c‐18∶2n−6 is not likely to be due to differences in the ability ofc,c‐18∶2n−6 or 20∶4n−6, or their matabolites, to activate PKC.
Lymphatic absorption of oxidized cholesterol in rats
Authors: Osada Kyoichi , Sasaki Eiji , Sugano Michihiro
Published: November 2006

The absorption of cholesterol and of cholesterol oxidation products (oxidized cholesterols) was compared in lymph‐cannulated rats. We found that the lymphatic absorption of an intragastrically administered, emulsified lipid meal containing 25 mg of cholesterol or 25 mg of oxidized cholesterols, within 24 h, was approximately 67 and 30%, respectively. The absorption rate of individual oxidized cholesterols differed considerably and was approximately 30% for 7α‐hydroxycholesterol, 42% for 7β‐hydroxycholesterol, 32% for 5β‐epoxycholesterol, 28% for 5α‐epoxycholesterol, 15% for cholestanetriol and 12% for 7‐ketocholesterol. Moreover, cholesterol oxidation products delayed the absorption of oleic acid as triolein. Approximately 35 and 48% of cholesterol was recovered in chylomicrons (CM) and very low density lipoprotein (VLDL), respectively. In contrast, 54 and 40% of the oxidized cholesterols was recovered in CM and VLDL, respectively, although there was a significant difference in the distribution of individual oxidized cholesterols. The results of the present study indicate that oxidized cholesterols are absorbed to a lesser extent than is cholesterol, that they disturb fat absorption and that they distribute differently between lymphatic lipoproteins.
Effects of n−3 and n−6 fatty acids on the activities and expression of hepatic antioxidant enzymes in autoimmune‐prone NZB×NZW F1 mice
Authors: Venkatraman Jaya T. , Chandrasekar Bysani , Kim Jong Dai , Fernandes Gabriel
Published: November 2006

Menhaden fish oil (FO) containing n−3 fatty acids dramatically extends the life span and delays the onset and progression of autoimmune disease in (NZB×NZW)F1 (B/W) female mice as compared to those fed corn oil (CO) rich in n−6 lipids. As an inefficient antioxidant defense system has been linked to autoimmune diseases, the present study was undertaken to determine whether the protective action of n−3 lipids is mediated through their antioxidant defense system. Weanling B/W mice were fed a nutritionally adequate, semipurified diet containing CO or krill oil (KO) or FO at 10% level (w/w)ad libitum until the mice were 6.5 months old. All diets contained the same level of vitamin E (21.5 mg/100 g diet). We compared the effects of feeding n−6 and n−3 lipids on survival, kidney disease, hepatic microsomal lipid composition, peroxidation, and on the activity and mRNA expression of the antioxidant enzymes catalase, glutathione peroxidase (GSH‐Px) and superoxide dismutase (SOD) in 6.5‐month‐old B/W mice. The results showed that when compared to livers from CO‐fed mice, livers from KO‐ and FO‐fed mice showed: (i) significantly higher (P<0.001) activities and expression of CAT, GSH‐Px and SOD; (ii) significantly lower (P<0.001) arachidonic acid (20∶4n−6) and linoleic acid (18∶2n−6) and higher (P<0.001) eicosapentaenoic acid (20∶5n−3) and docosahexaenoic acid (22∶6n−3) levels in hepatic microsomes; and (iii) significantly lower (P<0.001) estimated peroxidation indices and thiobarbituric acid reactive substances generation. The data indicate that one of the mechanisms through which the n−3 lipids delay the onset of autoimmune diseases in B/W mice may be through maintenance of higher activities and expression of hepatic antioxidant enzymes.
Serum fatty acid profiles in cystic fibrosis patients and their parents
Authors: Christophe A. B. , Warwick W. J. , Holman R. T.
Published: November 2006

Fatty acid compositions of the major serum lipid classes from 43 cystic fibrosis (CF) homozygotes (CF patients), 36 obligate heterozygotes (parents of CF patients) and 34 controls were determined by capillary gas chromatography. Fatty acid compositions of the homozygote CF patients were skewed in the direction of relative essential fatty acid deficiency in comparison with the controls. Less pronounced, but similar deviations from normal, were observed in the heterozygotes. Homozygotes with normal fatty acid compositions and heterozygotes with considerably disturbed fatty acid profiles were found.
A microprecipitation technique suitable for measuring α‐lipoprotein cholesterol
Authors: Puppione Donald L. , Charugundla Sarada
Published: November 2006

A semi‐automated method has been developed for determining α‐lipoprotein cholesterol values. Precipitation of apolipoprotein B containing lipoproteins takes place in wells of microtiter plates after 100 μL of serum are mixed with 20 μL of a heparin/MnCl2 solution. A Beckman (Fullerton, CA) Biomek 1000 work station is used to transfer sera, supernatants and reagents between tubes and microtiter plates. Supernatant cholesterol is determined enzymatically, and absorbances are read at 490 nm using a Molecular Devices Corporation (Palo Alto, CA) plate reader. Values obtained on both fresh and frozen serum samples agreed with corresponding data obtained at the Centers for Disease Control (CDC; Atlanta, GA). For the fresh samples, the average bias was 2.87%. The within‐run coefficients of variations were between 2.2 and 0.6% for the data obtained on CDC frozen control pools. The results indicate that the semi‐automated method is suitable for obtaining accurate and precise data for α‐lipoprotein cholesterol. The method lends itself to the analysis of large numbers of samples and is particularly suited for the study of lipoproteins of small mammals.
The effects of dietary fish oil on alveolar type II cell fatty acids and lung surfactant phospholipids
Authors: Baybutt Richard Carleton , Smith John Edgar , Yeh Yu‐Yan
Published: November 2006

The purpose of this study was to determine the responsiveness of alveolar type II cells to dietary fish oil and the consequent effects on alveolar and lung surfactant. Rats were fed a corn oil or a fish oil diet for four weeks. Dietary n−3 fatty acids were readily incorporated into the type II cell phospholipids as indicated by higher levels of eicosapentaenoic acid (2.77±0.10%) and docosahexaenoic acid (1.63±0.10%) in the group receiving the fish oil diet. The elevated levels of n−3 fatty acids were accompanied by concomitant reduction in arachidonic acid and linoleic acid. Neither eicosapentaenoic acid nor docosahexaenoic acid was incorporated into type II cell triacylglycerols. Feeding a fish oil containing diet increased surfactant phospholipids, particularly 1,2‐disaturated acyl phosphatidylcholines in whole lung compared to a corn oil diet. However, the amount of surfactant found in the alveolus was not different between the two diet treatment groups. The results suggest that dietary n−3 fatty acids stimulate synthesis and/or inhibit degradation of lung surfactant without altering surfactant secretion in alveoli.
Turnover of cholesterol and dipalmitoyl phosphatidylcholine in surfactant of adult rat lung
Authors: Jones Michael E. , Barr Heather A. , Nicholas Terence E.
Published: November 2006

In order to compare the turnover of two major surfactant components, [1α,2α(n)‐3H]cholesterol and [methyl14C choline] dipalmitoyl phosphatidylcholine (DPPC) were introduced as lamellar bodiesvia the trachea into lightly anesthetized rats which were then allowed to recover. The radiotracers were assumed to have entered the alveolar surfactant pool and to have subsequently recycled in part into the lamellar bodies of alveolar type II cells. For DPPC, the specific activityvs. time curves of tubular myelin rich (alv‐1) and tubular myelin poor (alv‐2) alveolar lavage fractions were similar, and there was a plausible precursor‐product relationship between lamellar bodies and either (or both) of these compartments. In contrast, however, the specific activities of alv‐1 and alv‐2 for cholesterol were quite different, allowing us to reject the hypothesis of a precursor‐product relationship between classical lamellar bodies and alv‐2. The estimated turover time for DPPC in alv‐1 was 240 or 206 min, depending on which subfraction of lamellar bodies one takes to be the precursor. For cholesterol it was 583 or 624 min. These longer turnover times for cholesterol should lead to a greater than twofold increase in the relative concentration of cholesterol in the putative product compartment. Such an increase was not found. We interpret this as reflecting either noncompartmental behavior of the alveolar surfactant pool, or multiple pools of lamellar bodies with different turnover times. We conclude that two major components of pulmonary surfactant, cholesterol and DPPC, are handled differently, and that for at least one of these substances, the widely accepted scenario of a compartmental precursor‐product relationship between lamellar bodies and alveolar surfactant must be rejected.
Hypolipidemic effects of β‐cyclodextrin in the hamster and in the genetically hypercholesterolemic rico rat
Authors: Riottot Michel , Olivier Philippe , Huet Anne , Caboche Jean‐Jacques , Parquet Michel , Khallou Jamila , Lutton Claude
Published: November 2006

The effect of increasing amounts of a cyclic oligosaccharide, β‐cyclodextrin (BCD), included in the diet on plasma cholesterol and triglycerides, was investigated in two animal models, namely in male genetically hypercholesterolemic Rico rats and in male Syrian hamsters. The distribution of bile acids in the gastrointestinal tract and in the feces of hamsters was also determined. In the Rico rats and hamsters, plasma cholesterol and triglycerides decreased linearly with increasing doses of BCD. In these two species, 20% BCD as compared to control diet lowered cholesterolemia (−35%) and triglyceridemia (−70%). In the hamster, the BCD diet caused a marked decrease in cholesterol and triglycerides in chylomicrons and very low density lipoprotein, and in high density lipoproteins cholesterol. Composition and amounts of bile acids were modified in the gastrointestinal tract of hamsters receiving 10% BCD as compared to the control group. The total bile acid content of the gallbladder of treated hamsters was fourfold higher than in the control group, and the bile contained a large amount of hydrophilic bile acids. This trend was also observed in the small intestine, in which percentages and total quantities of cholic plus deoxycholic acids (cholic pathway) were higher than those of chenodeoxycholic plus ursodeoxycholic plus lithocholic acids (chenodeoxycholic pathway). The bile acid contents of the cecum and colon of treated hamsters were 2.7‐fold higher than those of control animals, but the bile acid composition was similar in the two groups of hamsters. Fecal excretion of bile acids was 3.3‐fold higher in the treated group than in the control group, and the percentage of lithocholic acid was markedly increased and close to that observed in the colon. The turnover of the chenodeoxycholic pool was twice as fast in treated hamsters as in control hamsters, whereas that of cholic acid was not significantly modified. These results suggest that BCD does not alter the microbial degradation of bile acids, but rather stimulates their synthesis and increases their pool size. BCD prevents the intestinal absorption of lithocholic acid and washes this cytotoxic bile acid from the colon. The hypocholesterolemic effect of BCD appears to be due to stimulation of bile acid synthesis.
Human platelets release a paf‐acether: Acetylhydrolase similar to that in plasma
Authors: Korth Ruth , Bidualt Jocelyne , Palmantier Remi , Benveniste Jacques , Ninio Ewa
Published: November 2006

Intact washed human platelets aggregated in response to paf‐acether (paf) and did not metabolize [3H]paf at concentrations up to 10 nM. However, when platelets were lysed by exposure to pH 9.5, resulting in 37.5±2.5% (mean ±SD, n=3) lactic dehydrogenase (LDH) release, 20.5±5.7% of the radioactivity was detected as labeled lyso paf and 5.7±3.1% as labeled alkylacylglycerophosphocholine. When platelets were aggregated with 0.5 IU/mL thrombin or high concentrations of paf (100 nM), they released a part of their acetylhydrolase without releasing LDH. In supernatants obtained from aggregated platelets, 21±2% or 10±2% (n=3), respectively, of the total platelet acetylhydrolase activity was detectedvs. none in supernatants of resting cells. The release of acetylhydrolase was concentration‐and time‐dependent and paralleled the release of PF 4, a marker for α‐granules. The acetylhydrolase affinity for paf (Km) measured in sonicates of resting and thrombin‐activated platelets was 8.3±1.5 μMvs. 10.6±1.5 μM, n=5, n.s. in a “Mann Whitney” test. The latter Km was slightly but significantly different (P<0.05, n=5) from that of the thrombin‐released acetylhydrolase (7.9 ±1.5 μM) and that of the latter was itself different from plasma acetylhydrolase (5.3±0.5,P<0.05, n=5). Addition of plasma (acid‐treated to inactivate acetylhydrolase) decreased the Km value of supernatant acetylhydrolase to 6.1±1.4 μM. All preparations of acetylhydrolase exhibited similar pH requirements and sensitvity to various inhibitors. Thus paf and thrombin cause release of acetylhydrolase from platelets in parallel with release of the α‐granule marker PF4. This phenomenon might represent a protective mechanism against paf‐mediated effects in thrombotic and cardiovascular diseases.
Reaction of α‐tocopherol with alkyl and alkylperoxyl radicals of methyl linoleate
Authors: Yamauchi Ryo , Miyake Nobuyuki , Kato Koji , Ueno Yoshimitsu
Published: November 2006

α‐Tocopherol was reacted with alkyl and alkylperoxyl radicals at 37°C in bulk phase. The lipid‐free radicals were generated by the reaction of methyl linoleate with the free radical initiator, 2,2′‐azobis(2,4‐dimethylvaleronitrile) (AMVN) under air‐insufficient conditions. The products were isolated by high‐performance liquid chromatography. Their structures were identified as 2‐(α‐tocopheroxy)‐2,4‐dimethylvaleronitrile (1), a mixture of methyl 9‐(8a‐peroxy‐α‐tocopherone)‐10(E),12(Z)‐octadecadienoate and methyl 13‐(8a‐peroxy‐α‐tocopherone)‐9(Z),11(E)‐octadecadienoate (2), methyl 9‐(α‐tocopheroxy)‐10(E),12(Z)‐octadecadienoate (3a), methyl 13‐(α‐tocopheroxy)‐9(Z),11(E)‐octadecadienoate (3b), α‐tocopherol spirodiene dimer (4) and α‐tocopherol trimer (5). When methyl linoleate containing α‐tocopherol was oxidized with AMVN under airsufficient conditions, the main products were 8a‐alkyl‐peroxy‐α‐tocopherones (2). In addition to these compounds, 6‐O‐alkyl‐α‐tocopherols (1, 3a and 3b) were formed when the reaction was carried out under air‐insufficient conditions. The results indicate that α‐tocopherol can react with both alkyl and alkylperoxyl radicals during the autoxidation of polyunsaturated lipids.