bluuebunny/crossref_metadata_2025 huggingface dataset:
Abietoid seed fatty acid composition—A review of the genera Abies, Cedrus, Hesperopeuce, Keteleeria, Pseudolarix, and Tsuga and preliminary inferences on the taxonomy of Pinaceae
Authors: Wolff Robert L. , Lavialle Oliver , Pédrono Frédérique , Pasquier Elodie , Destaillats Frédéric , Marpeau Anne M. , Angers Paul , Aitzetmüller Kurt
Published: November 2006

The seed fatty acid (FA) compositions of Abietoids (Abies, Cedrus, Hesperopeuce, Keteleeria, Pseudolarix, and Tsuga) are reviewed in the present study in conclusion to our survey of Pinaceae seed FA compositions. Many unpublished data are given. Abietoids and Pinoids (Pinus, Larix, Ficea, and Pseudotsuga)—constituting the family Pinaceae—are united by the presence of several Δ5‐olefinic acids, taxoleic (5,9–18∶2), pinolenic (5,9,12–18∶3) coniferonic (5,9,12,15–18∶4), keteleeronic (5,11–20∶2), and sciadonic (5,11,14–20∶3) acids, and of 14‐methyl hexadecanoic (anteiso‐17∶0) acid. These acids seldom occur in angiosperm seeds. The proportions of individual Δ5‐olefinic acids, however, differ between Pinoids and Abietoids. In the first group, pinolenic acid is much greater than taxoleic acid, whereas in the second group, pinolenic acid is greater than or equal to taxoleic acid. Moreover, taxoleic acid in Abietoids is much greater than taxoleic acid in Pinoids, an apparent limit between the two subfamilies being about 4.5% of that acid relative to total FA. Tsuga spp. appear to be a major exception, as their seed FA compositions are much like those of species from the Pinoid group. In this respect, Hesperopeuce mertensiana, also known as Tsuga mertensiana, has little in common with Abietoids and fits the general FA pattern of Pinoids well. Tsuga spp. and H. mertensiana, from their seed FA compositions, should perhaps be separated from the Abietoid group and their taxonomic position revised. It is suggested that a “Tsugoid” subfamily be created, with seed FA in compliance with the Pinoid pattern and other botanical and immunological criteria of the Abietoid type. All Pinaceae genera, with the exception of Pinus, are quite homogeneous when considering their overall seed FA compositions, including Δ5‐olefinic acids. In all cases but one (Pinus), variations from one species to another inside a given genus are of small amplitude. Pinus spp., on the other hand, have highly variable levels of Δ5‐olefinic acids in their FA compositions, particularly when sections (e.g., Cembroides vs. Pinus sections) or subsections (e.g., Flexiles and Cembrae subsections from the section Strobus) are compared, although they show qualitatively the same FA patterns characteristic of Pinoids. Multicomponent analysis of Abietoid seed FA allowed grouping of individual species into genera that coincide with the same genera otherwise characterized by more classical botanical criteria. Our studies exemplify how seed FA compositions, particularly owing to the presence of Δ5‐olefinic acids, may be useful in sustaining and adding some precision to existing taxonomy of the major family of gymnosperms, Pinaceae.
Assessment of dietary and genetic factors influencing serum and adipose fatty acid composition in obese female identical twins
Authors: Kunešová Marie , Hainer Vojtěch , Tvrzická Eva , Phinney Stephen D. , Štich Vladimír , Pařízková Jana , Zák Aleš , Stunkard Albert J.
Published: November 2006

Fourteen pairs of obese female monozygotic twins were recruited for a study of genetic influences on serum and adipose fatty acid (FA) composition. Following 1 wk of inpatient stabilization, fasting serum and adipose tissue obtained by surgical excision were analyzed by thin‐layer and gas chromatography. Intrapair resemblances (IPR) for individual FA were assessed by Spearman rank correlation and by analysis of variance and were found in serum cholesteryl esters (CE), triglycerides (TG), and adipose TG. With two exceptions (CE linoleate and adipose eicosapentaenoate), these IPR were limited to the nonessential FA. Palmitate had significant IPR in four lipid fractions; in serum CE and adipose TG palmitate was strongly correlated with multiple measures of adiposity. In contrast to other lipid fractions, serum phosphatidylcholine (PC) FA had 12 IPR, of which 6 were essential FA including arachidonate (r=0.76, P<0.0005), eicosapentaenoate (r=0.78, P<0.0005), and docosahexaenoate (r=0.86, P<0.0001). The PC IPR could not be explained by analysis of preadmission 7‐d food records. After dividing the pairs into two groups differing and nondiffering according to fat intake of individuals in the pair, there was no evidence of a gene‐environment interaction between fat intake and FA composition. The IPR for nonessential FA indicate that there is active genetic control of either food choices or postabsorptive metabolic processing. The high level of IPR in the PC fraction in contrast to the other lipid fractions suggests strong genetic influence over selection of specific FA for this membrane fraction independent of diet.
Plant sterol esters lower plasma lipids and most carotenoids in mildly hypercholesterolemic adults
Authors: Judd Joseph T. , Baer David J. , Chen Shirley C. , Clevidence Beverly A. , Muesing Richard A. , Kramer Matthew , Meijer Gert W.
Published: November 2006

The ability of plant sterol esters (PSE) in salad dressing to modify plasma lipids and carotenoids was determined in 26 men and 27 women fed controlled, weight‐maintaining, isocaloric diets. Diets contained typical American foods that provided 32% of energy from fat. Dressings contained 8 g (ranch) or 4 g (Italian) of fat per serving. PSF (3.6 g/d) were provided in two servings/d of one of the dressings. Diets with ranch or Italian dressing without and with PSE were fed for 3 wk/diet and crossed over randomly within dressings. Diets were adjusted to similar fat and fatty acid concentrations. Type of salad dressing did not affect plasma lipids, lipoproteins, carotenoids, or fat‐soluble vitamins (P>0.05). Switching from a self‐selected baseline diet to the control diet resulted in reduction in low density lipoprotein (LDL) cholesterol of 7.9%, a decrease in high density lipoprotein (HDL) cholesterol of 3.1%, and a decrease in triglycerides (TG) of 9.3%. Consumption of 3.6 g of PSE resulted in further decreases in LDL cholesterol (9.7%) and TG (7.3%) but no additional change in HDL cholesterol. Total plasma carotenoids decreased 9.6% with PSE. An automated stepwise procedure was developed to produce candidate mixed models relating plasma carotenoid response to PSE. These models adjusted for preintervention plasma carotenoid levels and effects of diets on blood lipids. There were significant decreases in β‐carotene, α‐carotene, and β‐cryptoxanthin (females only) not associated with changes in plasma lipids. Plasma carotenoids on all diets remained within normal ranges. We conclude that low‐fat foods, such as salad dressings, are effective carriers for PSE.
Selective effect of cholesterylphosphoserine on intracellular cholesterol transport
Authors: Cusinato F. , Bruni A.
Published: November 2006

Cholesteryl‐3β‐phosphoserine (CPHS) is a synthetic steroid affecting intracellular cholesterol transport. To compare CPHS with the well‐known inhibitors progesterone and U18666A, we examined cholesterol transport in three human cell lines: the monocytic U‐937, the endothelial ECV‐304, and the lymphoid Jurkat. Under low density lipoprotein (LDL) loading, CPHS inhibited cholesterol esterification in U‐937 and ECV‐304 cells but not in Jurkat cells. In contrast, CPHS inhibited the mobilization of plasma membrane cholesterol induced by 25‐hydroxycholesterol, brefeldin A, or sphingomyelinase in all cell lines. In cells pulse‐labeled with [3H] cholesterol, CPHS decreased incorporation of cholesterol and inhibited its esterification. In prelabeled cells, CPHS promoted cholesterol efflux and enhanced the cyclodextrin‐mediated removal of plasma membrane cholesterol. CPHS did not affect endogenous cholesterol synthesis nor acylcoenzyme A: cholesterol acyltransferase activity. These data suggest that, unlike progesterone and U18666A, CPHS inhibits intracellular cholesterol transport by specifically affecting the movements of cholesterol in the plasma membrane. Owing to this restricted site of action, CPHS may help to clarify the role of the plasma membrane in cholesterol trafficking. For example, the lack of an effect of CPHS on the esterification of LDL‐derived cholesterol in Jurkat cells suggests that most of the LDL‐derived cholesterol in these cells is directly delivered to the endoplasmic reticulum without cycling through the plasma membrane.
Reduced secretion of triacylglycerol in CaCo‐2 cells transfected with intestinal fatty acid‐binding protein
Authors: Gedde‐Dahl Ane , Kulseth Mari Ann , Ranheim Trine , Drevon Christian A. , Rustan Arild C.
Published: November 2006

The fatty acid‐binding proteins are hypothesized to be involved in cellular fatty acid transport and trafficking. We established CaCo‐2 cells stably transfected with intestinal fatty acid‐binding protein (I‐FABP) and examined how the expression of this protein may influence fatty acid metabolism. I‐FABP expression was detectable in I‐FABP‐transfected cells, whereas parent CaCo‐2 cells as well as mock‐transfected cells failed to express detectable levels of I‐FABP mRNA or protein at any stage of differentiation. For studies of lipid metabolism, cells were incubated with [14C]oleic acid in taurocholate micelles containing monoolein, and distribution of labeled fatty acid in cellular and secreted lipids was examined. In one transfected cell clone, expressing the highest level of I‐FABP, labeled cellular triacylglycerol increased approximately twofold as compared to control cells. The level of intracellular triacylglycerol in two other I‐FABP‐transfected clones resembled that of control cells. However, secretion of triacylglycerol was markedly reduced in all the I‐FABP‐expressing cell lines. Our data suggest that increased expression of I‐FABP leads to reduced triacylglycerol secretion in intestinal cells.
Regulation of phosphatidic acid phosphohydrolase 1 by fatty acids
Authors: Elabbadi Noureddine , Day Christopher P. , Virden Richard , Yeaman Stephen J.
Published: November 2006

In the starved state and during metabolic stress, free fatty acids (FFA) are the principal hepatic energy supply, undergoing β‐oxidation. Accordingly, it appears paradoxical that H‐A have been reported to increase the liver's esterification capacity by translocating the rate‐limiting enzyme phosphatidic acid phosphohydrolase (PAP‐1) from the cytosol to the endoplasmic reticulum. We have therefore investigated the regulation of rat liver PAP‐1. Oleic acid inhibited PAP activity in all subcellular fractions, with PAP‐1 activity in cytosol being the most sensitive. Inhibition was also observed with oleoyl‐CoA, linoleate, and palmitate. Fatty acids and their derivatives show detergent effects at high concentrations, and such effects can lead to enzyme inhibition. Inhibition by oleate, however, was reversed by phosphatidic acid and albumin and exhibited sigmoidal kinetics. These results demonstrate that PAP‐1 is reversibly inhibited by FFA and their CoA esters, which may play a role in directing hepatic FFA to β‐oxidation during times of increased energy demand.
Formation of triacylglycerol core aldehydes during rapid oxidation of corn and sunflower oils with tert‐butyl hydroperoxide/Fe2+
Authors: Sjövall Olli , Kuksis Arnis , Kallio Heikki
Published: November 2006

The lipid ester core aldehydes formed during a rapid oxidation (7.8 M tert‐butyl hydroperoxide, 90 min at 37°C) of the triacylglycerols of purified corn and sunflower oils were isolated as dinitrophenylhydrazones by preparative thin‐layer chromatography and identified by reversed‐phase high‐performance liquid chromatography with on‐line electrospray ionization mass spectrometry and by reference to standards. A total of 113 species of triacylglycerol core aldehydes were specifically identified, accounting for 32–53% of the 2,4‐dinitrophenylhydrazine (DNPH)‐reactive material of high molecular weight representing 25–33% of the total oxidation products. The major core aldehyde species (50–60% of total triacylglycerol core aldehydes) were the mono(9‐oxo)nonanoyl‐ and mono(12‐oxo)‐9,10‐epoxy dodecenoyl‐ or (12‐oxo)‐9‐hydroxy‐10,11‐dodecenoyl‐diacylglycerols. A significant proportion of the total (9‐oxo)nonanoyl and epoxidized (12‐oxo)‐9,10‐dodecenoyl core aldehydes was found in complex combinations with hydroperoxy or hydroxy fatty acyl groups (6–10% of total triacylglycerol core aldehydes). Identified were also di(9‐oxo)nonanoylmonoacylglycerols (0.5% of total) and tri(9‐oxo)nonanoylglycerols (trace). The identification of the oxoacylglycerols was consistent with the products anticipated from tert‐butyl hydroperoxide oxidation of the major species of corn and sunflower oil triacylglycerols (mainly linoleoyl esters). However, the anticipated (13‐oxo)‐9,11‐tridecadienoyl aldehyde‐containing acylglycerols were absent because of further oxidation of the dienoic core aldehyde. A significant proportion of the unsaturated triacylglycerol core aldehydes contained tert‐butyl groups linked to the unsaturated fatty chains via peroxide bridges (2–9%). The study demonstrates that rapid peroxidation with tert‐butyl hydroperoxide consitutes an effective method for enriching natural oils and fats in triacylglycerol core aldehydes for biochemical and metabolic testing.
Dietary cis and trans monounsaturated and saturated FA and plasma lipids and lipoproteins in men
Authors: Judd Joseph T. , Baer David J. , Clevidence Beverly A. , Kris‐Etherton Penny , Muesing Richard A. , Iwane Marika
Published: November 2006

Trans monounsaturated fatty acids (TFA) are hypercholesterolemic compared to oleic acid to a degree approaching or equivalent to saturated FA. However, it is unknown to what extent these effects may be due to cholesterol lowering by oleic acid rather than elevation by saturated FA and TFA. In order to better understand the impact of replacing TFA in foods, it is first necessary to know the relative lipid‐modifying effects of the major FA that change as TFA are lowered or removed. For 5 wk, 50 normocholesterolemic men were fed controlled diets providing approximately 15% of energy from protein, 39% from fat, and 46% from carbohydrate in a randomized, 6×6, crossover design. Eight percent of energy was replaced across diets with the following: carbohydrate (CHO) (1∶1 simple to complex); oleic acid (OL); TFA; stearic acid (STE); TFA/STE (4% of energy from each); carbon 12∶0 16∶0 saturated FA (LMP). LDL cholesterol concentrations (mmol/l) were as follows (different superscripts indicate significance at P≤0.01): OL 2.95a; CHO 3.05a,b; STE 3.10b,c; LMP 3.21c,d; TFA+STE 3.32d,e; and TFA 3.36e. HDL cholesterol concentrations (mmol/L) were as allows: STE 1.16a; IFA 1.16a,b; TFA/STE 1.17a,b; CHO 1.19b; OL 1.24c; and LMP 1.30d. Triacylglycerides were highest after STE (1.13) and lowest after OL (0.88) (P<0.001). Thus, compared to the carbohydrate control diet, TFA raised LDL cholesterol at least equivalent to LMP but had no effect on HDI cholesterol; STE had no effect on LDL cholesterol but lowered HDL cholesterol; LMP raised both LDL cholesterol and HDL cholesterol; and oleic acid raised HDL cholesterol but had no effect on LDL cholesterol.
Maternal supplementation with CLA decreases milk fat in humans
Authors: Masters Nicole , McGuire Mark A. , Beerman Kathy A. , Dasgupta Nairanjana , McGuire Michelle K.
Published: November 2006

CLA refers to isomers of octadecadienoic acid with conjugated double bonds. The most abundant form of CLA (rumenic acid (RA): c9,t11‐18∶2) is found in milk and beef fat. Further, CLA supplements containing RA and t10,c12−18∶2 are now available. Consumption of commercially produced CLA has been shown to decrease adipose accretion in growing laboratory and production animals and cause milk fat depression in cows. We tested the hypothesis that CLA supplementation would increase milk CLA concentration and decrease milk fat content in humans. Breastfeeding women (n=9) participated in this double‐blind, placebo‐controlled, crossover study divided into three periods: intervention l (5 d), washout (7 d), and intervention II (5 d). Women were randomized to treatment order. During each intervention period, women consumed 1.5 g of CLA supplement or placebo (olive oil) daily; during the washout period, no supplements were consumed. Milk was collected by complete breast expression on the final day of each period; milk output was estimated by 24‐h weighing on the penultimate day of each intervention period. Milk RA and t10,c12−18∶2 concentrations were greater (P<0.05) during the CLA treatment period as compared to the placebo period. Milk fat content was significantly lower during the CLA treatment, as compared to the placebo treatment (P<0.05). Data indicate no effect of treatment on milk output. Therefore, it would be prudent that lactating women not consume commercially available CLA supplements at this time.
Characterization of the adipose tissue atrophy induced by peroxisome proliferators in mice
Authors: Xie Yi , Yang Qian , Nelson B. Dean , DePierre Joseph W.
Published: November 2006

In the present study, we characterized the effects of peroxisome proliferators (PP) on adipose tissue in mice. Treatment with potent PP, such as perfluorooctanoic acid (PFOA), 2‐methyl‐2‐(p(1,2,3,4‐tetrahydroxy‐naphthyl)‐phenoxy)propionic acid, (4‐chloro‐6‐(2,3‐xylidino)2‐pyrimidinylthio) acetic acid, and di(2‐ethylhexyl)phthalate, caused dramatic decreases in adipose tissue weight, whereas the moderately potent PP, acetylsalicylic acid, had a relatively weak effect. This decrease in weight reflects a loss of fat from adipocytes rather than a loss of cells, as demonstrated by constant DNA content. The dose‐dependency and time‐course experiments indicate that peroxisome proliferation occurs simultaneously with or prior to adipose tissue atrophy. Thus, hepatic peroxisome proliferation might result in the increased mobilization of lipids and lipid utilization in liver. The enhanced adipose tissue hormonesensitive lipase (HSL) activity and down‐regulated lipoprotein lipase (LPL) activity observed upon PP treatment might, at least in part, explain the loss of fat via increase FA release from adipocytes and/or decreased FA uptake from the circulation, respectively. In addition, the possible involvement of the increased tumor necrosis factor α expression found upon PFOA treatment in reducing the insulin sensitivity of adipose tissue and thereby altering LPL and HSL activities is discussed.
Improvement of vascular dysfunction and blood lipids of insulin‐resistant rats by a marine oil‐based phytosterol compound
Authors: Russell James C. , Ewart H. Stephen , Kelly Sandra E. , Kralovec Jaroslav , Wright Jeffrey L. C. , Dolphin Peter J.
Published: November 2006

The syndrome that is characterized by obesity, insulin resistance, and hyperlipidemia is increasingly prevalent in all prosperous societies. It is now recognized as a major contributor to cardiovascular disease. Vascular dysfunction in the form of hypercontractility and impaired nitric oxide‐mediated relaxation is a significant component of cardiovascular disease, predisposing to ischemic events. The JCR:LA‐cp strain of rats exhibits all major aspects of the obesity/insulin resistance syndrome, including vascular dysfunction and ischemic lesions of the heart. Dietary lipid intake may have a marked effect on plasma lipid levels and, potentially, on vascular disease. We have investigated the effects of a novel preparation, ONC101 (a phytosterol esterified with fish oil), on plasma lipids and vascular function in the insulin‐resistant JCR:LA‐cp rat. Treatment of obese male rats with ONC101 from 8 to 12 wk of age resulted in no change in plasma lipid concentrations at 0.5 g/kg body weight. At the higher dose of 2.6 g/kg, plasma TG fell 50% (1.26 vs. 2.59 mmol/L, P<0.002) and cholesterol esters were significantly reduced (1.34 vs. 1.61 mmol/l, P<0.002). Food intake and body weights were unaffected by ONC101 treatment. At the low dose of 86 mg/kg, the hypercontractility of aortic rings in response to phenylephrine was normalized and the relaxant response to acetylcholine was significantly improved. The results indicate that ONC101 at high doses has significant hypolipidemic effects and, at very low doses, has beneficial effects on endothelial and vascular smooth muscle cell function.
Evidence that leptin contributes to intestinal cholesterol absorption in obese (ob/ob) mice and wild‐type mice
Authors: Igel M. , Lindenthal B. , Giesa U. , von Bergmann K.
Published: November 2006

In the present study, the effect of leptin on intestinal cholesterol absorption was investigated in C57 BL/6 OlaHsd Lepob/Lepob obese (ob/ob) mice and lean C57 BL/6 (wild‐type) mice. Animals were treated either with or without recombinant leptin for 2 wk. Cholesterol absorption was measured by the constant isotope feeding method and indirectly by the ratio of campesterol to cholesterol in serum. In ob/ob mice, cholesterol absorption was significantly higher compared to wild‐type mice [83.4±2.3% (SD) vs. 77.6±1.5%, P<0.01]. Treatment with leptin significantly reduced cholesterol absorption in both ob/ob and wild‐type mice by 8.5 (P<0.001) and 5.2% (P<0.05), respectively. Serum concentrations of campesterol and the ratio of campesterol to cholesterol in ob/ob mice were significantly higher compared to wild‐type mice (2.2±0.3 mg/dL vs. 1.2±0.3 mg/dL, P<0.001; and 36.8±2.8 μg/mg vs. 28.0±3.3 μg/mg, P<0.001). After treatment of ob/ob mice with leptin, concentrations of campesterol and its ratio to cholesterol were significantly lower (2.2±0.3 mg/dL vs. 1.0±0.2 μg/mg, P<0.001; and 36.8±2.8 μg/mg vs. 13.2±2.2 μg/mg, P<0.001, respectively). In wild‐type mice, the ratio of campesterol to cholesterol in serum was also significantly lower after treatment with leptin (28.0±3.3 μg/mg vs. 22.6±5.0 μg/mg, P<0.05). A significant positive correlation (r=0.701, P<0.01) between cholesterol absorption and the ratio of campesterol to cholesterol, in serum was found. It is concluded that leptin contributes to intestinal cholesterol absorption in ob/ob mice and lean wild‐type mice.
Acute pancreatitis decreases pancreas phospholipid levels and increases susceptibility to lipid peroxidation in rat pancreas
Authors: Ferreira Laura , Pérez‐González Nieves , Llanillo Marcial , Julián Calvo Jose , Sánchez‐Bernal Carmen
Published: November 2006

The objective of this study was to analyze whether acute pancreatitis leads to changes in the lipid composition and susceptibility to lipid peroxidation of pancreatic membranes. Total lipids, cholesterol, phospholipids, FA, and lipid peroxidation were determined in the pancreatic tissue of rats treated with cerulein and of control rats. In pancreatitic rats, significant decreases in membrane total phospholipid contents (P<0.05) and in choline and ethanolamine glyceorphospholipid levels (P<0.05 and P<0.01, respectively), with concomitant significantly higher values of their lysoderivative forms, were found. The cholesterol/phospholipid molar ratio increased by 26%. The unsaturation index of the FA profile decreased significantly (P<0.01) as a consequence of a decrease in the arachidonic acid content. Incubation of membranes with xanthine oxidase/hypoxanthine‐Fe2+/ADP resulted in an increase in the production of TBARS in pancreatitic rats compared to controls. In summary, acute pancreatitis causes changes in the lipid composition of rat pancreatic crude membranes and a greater susceptibility of these membranes to lipid peroxidation.
γ‐Tocopheryl quinone stimulates apoptosis in drug‐sensitive and multidrug‐resistant cancer cells
Authors: Jones Kenneth H. , Liu Jennifer J. , Roehm Jennifer S. , Eckel Jason J. , Eckel Tobin T. , Stickrath Chad R. , Triola Craig A. , Jiang Zongcheng , Bartoli Gianna M. , Cornwell David G.
Published: November 2006

Chemotherapy‐induced cell death is linked to apoptosis, and there is increasing evidence that multidrug‐resistance in cancer cells may be the result of a decrease in the ability of a cell to initiate apoptosis in response to cytotoxic agents. In previous studies, we synthesized two classes of electrophilic tocopheryl quinones (TQ), nonarylating α‐TQ and arylating γ‐and δ‐TQ, and found that γ‐and δ‐TQ, but not α‐TQ, were highly cytotoxic in human acute lymphoblastic leukemia cells (CEM) and multidrug‐resistant (MDR) CEM/VLB100. We have now extended these studies on tumor biology with CFM, HL60 and MDR HL60/MX2 human promyelocytic leukemia, U937 human monocytic leukemia, and ZR‐75‐1 breast adenocarcinoma cells. γ‐TQ, but not α‐TQ or tocopherols, showed concentration and incubation time‐dependent effects on loss of plasma membrane integrity, diminished viable cell number, and stimulation of apoptosis. Its cytotoxicity exceeded that of doxorubicin in HL60/MX2 cells, which express MRP, an MDR‐associated protein. Apoptosis was confirmed by TEM, TUNEL, and DNA gel electrophoresis. Kinetic studies showed that an induction period was required to initiate an irreversible multiphase process. γ‐TQ released mitochondrial cytochrome c to the cytosol, induced the cleavage of poly(ADP‐ribose)polymerase, and depleted intracellular glutathione. Unlike xenobiotic electrophiles, γ‐TQ is a highly cytotoxic arylating electrophile that stimulates apoptosis in several cancer cell lines including cells that express MDR through both P‐glycoprotein and MRP‐associated proteins. The biological properties of arylating TQ electrophiles are closely associated with cytotoxicity and may contribute to other biological effects of these highly active agents.
Farnesol and geranylgeraniol: Prevention and reversion of lovastatin‐induced effects in NIH3T3 cells
Authors: Ownby Susan E. , Hohl Raymond J.
Published: November 2006

Mevalonic acid‐derived intermediates in the cholesterol biosynthetic pathway have been recognized as being critical to the isoprenylation of a variety of growth‐regulating proteins, including those of the RAS superfamily. Treatment of cells with lovastatin, a hydroxymethylglutaryl coenyme A (HMG‐CoA) reductase inhibitor, depletes cells of mevalonic acid and thus blocks the isoprenylation of proteins in the RAS superfamily. In NIH3T3 cells pretreated with lovastatin, subsequent addition of farnesol (FOH), but not geranylgeraniol (GGOH), reverses lovastatin's block of RAS isoprenylation. Neither FOH nor GGOH prevents lovastatin‐induced inhibition of RAS isoprenylation when added to cells concurrently with lovastatin. In intact cells, 167 μM FOH and 125 μM GGOH decrease incorporation of [14C]acetate into cholesterol by approximately 50 and 75%, respectively. Results suggest that the radiolabel from either [3H]FOH or [3H]GGOH is incorporated into cholesterol. Co‐treatment of cells with lovastatin or mevalonic acid did not significantly alter [3H]FOH or [3H]GGOH incorporation into cholesterol. Lovastatin induces cell rounding; GGOH, but not FOH, both prevents and reverses lovastatin‐induced cell rounding. These results provide additional evidence for the existence of a novel “isoprenoid shunt” that differentially utilizes FOH and GGOH as metabolic precursors for isoprenoids that have been depleted by lovastatin treatment.
Biosynthesis of arachidonic acid in the oleaginous microalga Parietochloris incisa (Chlorophyceae): Radiolabeling studies
Authors: Bigogno Chiara , Khozin‐Goldberg Inna , Adlerstein Daniel , Cohen Zvi
Published: November 2006

The fresh‐water green alga Parietochloris incisa is the richest plant source of the PUFA arachidonic acid (20∶4n−6, AA). To elucidate the biosynthesis of AA in this alga we labeled cultures of P. incisa with radioactive precursors. Pulse chase labeling with acetate resulted in its incorporation via the de novo biosynthesis pathway of FA. However, labeled acetate was also utilized for the elongation of C16 and C18 PUFA. Labeling with [1‐14C]oleic acid has shown that the first steps of the lipid‐linked FA desaturations utilize cytoplasmic lipids. PC and diacylglyceryltrimethylhomoserine are the major lipids involved as acyl carriers for the Δ12 and Δ6 desaturations of oleic acid, leading sequentially to linoleic and γ‐linolenic acids. The latter is released from its lipid carrier and elongated to 20∶3n−6, which is reincorporated primarily into PF and PC and finally desaturated to AA. Galactolipids, mostly monogalctosyldiacylglycerol (MGDG), serve as substrates for the chloroplastic Δ12 desaturase and, apparently, the ω3 desaturation, common to higher plants and many green algae. The predominant sequence desaturates the 18∶1/16∶0 molecular species of MGDG stepwise to the 18∶3n−3/16∶3n−3 molecular species similar to the prokaryotic pathway of higher plants and green algae.
Detection of the 15‐acetate of prostaglandin E2 methyl ester as a prominent component of the prostaglandins in the gorgonian coral Plexaura homomalla
Authors: Schneider Claus , Manier M. Lisa , Hachey David L. , Brash Alan R.
Published: November 2006

15R‐Prostaglandin E2 (PGE2) methyl ester 15‐acetate (1) was isolated from the R‐variety of the Caribbean sea whip coral, Plexaura homomalla collected in the Florida Keys. It was present in coral samples from separate collections in 2–10% of the abundance of the major prostaglandin component, PGA2 methyl ester 15‐acetate. The structure of 1 was assigned based on one‐ and two‐dimensional 1H NMR, HPLC, and LC‐MS analyses. A sample of the S‐variety of P. homomalla was found to contain a similar abundance of the corresponding 15S product, prostaglandin E2 methyl ester 15‐acetate. The significance of PGE acetylation is discussed in relation to the proposed mechanism of PGA synthesis in the coral.
Synthesis of (S)‐α‐amino oleic acid
Authors: Magrioti Victoria , Constantinou‐Kokotou Violetta
Published: November 2006

An efficient synthesis of (S)‐α‐amino oleic acid was developed. The fully protected FA derivative was obtained in four steps starting from methyl (2S)‐2‐[bis(tert‐butoxycar‐bonyl)amino]‐5‐oxopentanoate. These steps are (i) olefination of the starting aldehyde with the appropriate phosphonate anion, (ii) hydrogenation of the double bonds, (iii) controlled reduction of ω‐ethyl ester to an aldehyde in the presence of α‐methyl ester, and (iv) a Wittig reaction of the latter aldehyde with the suitable ylide. Free α‐amino oleic acid was prepared after deprotection of the amino group followed by saponification in a total yield of 24%. N‐tert‐Butoxycarbonyl‐protected amino oleic acid and the corresponding amino alcohol were prepared in high yield. The structures of the products have been established by various spectroscopic techniques.
Cardiac and vascular structure and function are related to lipid peroxidation and metabolism
Authors: Steer Peter , Millgård Jonas , Sarabi Dennis M. , Basu Samar , Vessby Bengt , Kahan Thomas , Edner Magnus , Lind Lars
Published: November 2006

The present study investigated possible relationships between left ventricular mass, intima‐media thickness of the carotid artery (IMT), total arterial compliance, and lipid status in a population sample of 58 apparently healthy subjects aged 20 to 69. By stepwise multiple regression analysis, including age, blood pressure, and smoking, left ventricular mass index, measured by M‐mode echocardiography, increased by 13.0 g/m2 for each 1 standard deviation (SD=0.11 μM, r=0.60, P<0.01) increase in plasma malondialdehyde and 9.50 g/m2 per SD increase in plasma 8‐iso‐prostaglandin F2α in women only (SD=8.88 ng/L, r=0.44, P=0.01). Each 1‐SD (SD=0.27 g/L) increase in apolipoprotein B was associated with a 63 μm increase in IMT (r=0.47, P=0.01) and a 0.27 mL/min/m2/mm Hg (r=−0.60, P<0.01) decrease in stroke index/pulse pressure ratio, reflecting total arterial compliance in women. In men, each 1‐SD increase in the proportion of stearic acid (18∶0) in serum cholesterol esters (SD=0.12 percent units) reduced the transmitral E/A ratio, measured by Doppler echocardiography, reflecting left ventricular diastolic function, by 0.10 units (r=−0.29, P<0.05). Thus, important cardiovascular characteristics, such as left ventricular mass, left ventricular diastolic function, carotid IMT, and total arterial compliance, were independently predicted by indices of lipid metabolism and peroxidation in apparently healthy subjects.
Dietary n−3 FA modulate long and very long chain FA content, rhodopsin content, and rhodopsin phosphorylation in rat rod outer segment after light exposure
Authors: Suh Miyoung , Wierzbicki Antony A. , Clandinin M. Thomas
Published: November 2006

A previous study has shown that the long and very long chain FA (VLCFA) content of the rat retina responds to changes in dietary n−6/n−3 ratio of the fat fed (1). The present study tested whether similar changes in these FA are associated with alterations in rhodopsin content and rhodopsin phosphorylation after light treatment. Weanling rats were fed diets containing 20% (w/w, 40% energy) fat with either high (4.8%, w/w) or low (1.2%, w/w) n−3 FA. After 6 wk of feeding, half of the animals in each group were exposed to light for 48 h at 350 lx or were kept in complete darkness. In the rod outer segment, the high n−3 diet treatment increased the level of 20∶5n−3 and 22∶6n−3 and reduced the levels of 20∶4n−6 and 24∶4n−6 in PC, PE, and PS. After the feeding of a high n−3 FA diet, total n−3 pentaenoic VLCFA from C24 to C34 increased in PC, whereas the n−6 tetra‐ and pentaenoic VLCFA decreased. No changes occurred in n−3 hexaenoic VLCFA regardless of the level of 22∶6n−3 in the diet. After light exposure, animals fed a high n−3 FA diet showed reduction in 22∶6n−3 as well as in n−6 and n−3 VLCFA in PC. FFA and TG fractions contained increased levels of both 20∶4n−6 and 22∶6n−3 after light exposure. Dark‐adapted rhodopsin content and rhodopsin phosphorylation in the rod outer segment of rats fed the low n−3 FA diet were higher than in animals fed a high n−3 FA diet. After light exposure, animals fed the low n−3 FA diet lost more rhodopsin compared to animals fed the high n−3 FA diet, resulting in less phosphorylation of rhodopsin. Results indicate that the FA composition, rhodopsin content, and phosphorylation in visual cells is influenced by the dietary n−3 FA fed as well as by light exposure. The results also imply that 22∶6n−3 may not be the precursor for synthesis of hexaenoic VLCFA.
Hypolipidemic action of the soybean isoflavones genistein and genistin in glomerulonephritic rats
Authors: Kojima Takashi , Uesugi Takehiko , Toda Toshiya , Miura Yutaka , Yagasaki Kazumi
Published: November 2006

Effects of genistein and its glycoside genistin were studied in nephritic rats with endogenous hyperlipidemia. Male Wistar rats with glomerulonephritis caused by a single intravenous injection of nephrotoxic serum were orally given 5 mg of genistein or 8 mg of genistin/d/100 g body weight for 12 d. These isoflavones suppressed nephritis‐induced severe hypercholesterolemia and hypertriglyceridemia, and their hypolipidemic action was almost identical. Fecal steroid excretion was unchanged by administration of the two isoflavones. Genistein inhibited the incorporation of [1‐14C]acetate into cholesterol and FA in liver slices from nephritic rats when added to an incubation buffer, whereas genistin did not. These results suggest that genistin may be hydrolyzed to genistein and that genistein itself and/or its metabolite(s) may be intracorporal entities suppressing hepatic lipid syntheses. They also suggest that the suppression of hepatic lipid synthesis may be one mechanism of the hypolipidemic action of genistein.
Egg ovomucin attenuates hypercholesterolemia in rats and inhibits cholesterol absorption in Caco‐2 cells
Authors: Nagaoka Satoshi , Masaoka Motoki , Zhang Qing , Hasegawa Mineo , Watanabe Kenji
Published: November 2006

This experiment was designed to evaluate the effect of casein or ovomucin (OV) on the micellar solubility of cholesterol and the taurocholate binding capacity in vitro. We also evaluated the effects of casein or OV on cholesterol metabolism in rats and Caco‐2 cells. OV has a significantly greater bile acid‐binding capacity than that of casein in vitro. Micellar cholesterol solubility in vitro was significantly lower in the presence of OV compared to casein. The cholesterol micelles containing OV significantly suppressed cholesterol uptake by Caco‐2 cells compared to the cholesterol micelles containing casein. Consistent with these in vitro findings, OV‐feeding significantly increased the fecal excretion of bile acids or cholesterol compared with casein‐feeding. Serum total cholesterol was significantly lower in rats fed OV than in those fed casein. The concentrations of total lipids in liver were significantly lower in the OV‐fed group compared with the casein group. These results suggest that the suppression of cholesterol absorption by direct interaction between cholesterol mixed micelles and OV in the jejunal epithelia is part of the mechanism underlying the hypocholesterolemic action of OV. OV may also inhibit the reabsorption of bile acids in the ileum, thus lowering the serum cholesterol level.
Evidence in favor of a facilitated transport system for FA uptake in cultured L6 cells
Authors: Marra Carlos A. , Girón María Dolores , Suáre María Dolores
Published: November 2006

In this manuscript we report a study of the transport of FA in L6 muscle cells. Cultured L6 cells took up labeled FA (C10 to C20) as a linear function of time up to 15 min. Thereafter, the rate of uptake gradually declined although it persisted for at least 12 h after the addition of the substrate. Kinetic parameters (Km, Vm, and ko) were determined from a fitted Michaelis‐Menten‐type equation modified by a term for a saturable (linear) component of the measured total uptake. Vm values were different for some of the FA studied, and Km data showed significant differences between saturated and unsaturated FA. The maximal rate of uptake was observed at pH 7.40 for decanoate, palmitate, and eicosatrienoate. Uptake was significantly influenced when the pH of the incubation medium was changed. Experiments designed to study the influence of FA/albumin molar ratio indicated that Vm was dependent on the total (bound and free) concentration of the FA. A concentrative uptake was demonstrated in short‐term experiments with an apparent plateau of 20 and 40 μM for palmitate and eicosatrienoate, respectively. A competitive inhibition was also observed between palmitate as substrate and the other FA. From our results we can postulate that the uptake of FA in L6 cells is the sum of passive diffusion plus a saturable component and that the rate of uptake is dependent on one (or more) protein structures, although their precise characteristics and functions remain to be elucidated.
Platelet phospholipids are differentially protected against oxidative degradation by plasmalogens
Authors: Leray Claude , Cazenave Jean‐Pierre , Gachet Christian
Published: November 2006

The oxidative degradation of phospholipids in the presence and absence of plasmalogens (plasmenyl phosphatidylethanolamine: PPE) was followed by chemical analysis. Human platelet phospholipids, either intact or after removal of PPE by acid treatment, were oxidized with 28 mM 2,2′‐azobis(2‐amidinopropane di‐HCl in Triton X‐100 micelles (detergent/phospholipid 5∶1, mol/mol). PPE (12% of all phospholipids, mol/mol) disappeared about three times more rapidly than glycerophospholipids, whereas sphingomyelin remained unaltered and the lysophosphatidylethanolamine (lysoPE) generated became progressively more unsaturated. After 60 min oxidation, the FA compositions of PS, PC, and PI were similar in extracts with or without plasmalogens. In contrast, diacyl phosphatidylethanolamine (DPE) became more saturated in the absence of PPE. The rate of phospholipid destruction was always unique to each class, but for all phospholipids slowed down in the presence of PPE. This protective effect increased in the order DPE<PS<PC<PI and did not seem to be simply related to the class unsaturation. α‐Tocopherol had no influence on the time courses of the quantities and compositions of the phospholipids, even at a molar ratio of α‐tocopherol to phospholipids four times higher than in platelet membranes. Thus, PPE protected phospholipids efficiently but differentially against peroxidative attack, whereas the contribution of α‐tocopherol appeared to be negligible even at a concentration four times greater than in platelet membranes.
Lung lipid composition in zinc‐deficient rats
Authors: Gomez N. N. , Ojeda M. S. , Gimenez M. S.
Published: November 2006

There have been a limited number of studies investigating surfactant lipid changes in lung with trace elements. The present investigation was designed to examine the effect of moderate zinc deficiency on the lipid metabolism in rat lung. We also evaluated whether zinc deficiency, which is a wide‐spread problem, could play a role in adult respiratory distress syndrome (ARDS). For that purpose, adult male Wistar rats were fed two diets differing in zinc concentration. The rats were divided into two groups. One group was fed a zinc‐deficient diet containing 3 mg Zn/kg, and the other group received a zincadequate control diet with 30 mg Zn/kg according to AIN 93‐M. After 2 mon of treatment, we observed that in the zinc‐deficient group (i) total lipids, phospholipids, and cholesterol increased whereas TG decreased in whole lung; (ii) phospholipid (PC) concentration increased in lamellar bodies and alveolar macrophages and decreased in extracellular surfactant but did not change in microsomes; (iii) protein concentration decreased in whole lung, extracellular surfactant, lamellar bodies, and macrophages; (iv) the incorporation of [Me‐14C]choline into PC (phospholipids) of lung slices increased; and (v) the activity of CTP/phosphocholine cytidylyltransferase bound to the microsomes increased in the lung. These results suggest that the lipid concentration in the lung (especially the phospholipids) is modified directly or indirectly by a zinc‐deficient diet. In a zincdeficient diet, the lung changes the pattern of PC for an adaptive or recovery stage. Therefore, zinc deficiency implications are important for the design of therapies and public health interventions involving targeted zinc supplementation for high‐risk groups or groups with certain diseases, such as ARDS.
Lipid metabolism and FA composition in tissues of Eurasian perch Perca fluviatilis as influenced by dietary fats
Authors: Xu Xueliang , Kestemont Patrick
Published: November 2006

Eurasian perch, Perca fluviatilis, were fed a semipurified fat‐free diet for 4 wk, followed by a 16% feeding supplementation of either olive oil (OO), safflower oil (SO), linseed oil (LO), or cod liver oil (CLO) as the only lipid source in each diet for 10 wk. Significant reductions in total lipid of tissues were observed (31.4% in viscera, 66.7% in muscle, and 74.1% in liver) after feeding the fat‐free diet. The SO‐, LO‐, and CLO‐fed fish significantly increased lipid deposition in liver and viscera compared to fish fed the OO diet; however, muscle lipid levels were not significantly affected. Large amounts of dietary 18∶1n−9 were incorporated directly into tissue lipids when fish were fed the OO diet. The LO diet significantly elevated 18∶4n−3, 20∶5n−3, 22∶5n−3, and 22∶6n−3 in the liver compared to fish fed OO or SO diets, and the n−3/n−6 ratio was 16 times that of the SO group, with significantly high desaturation and elongation products of 18∶3n−3. These results suggest that Δ6 and Δ5 desaturases are highly active in Eurasian perch, and that the enzymes at this dietary n−3/n−6 ratio favor 18∶3n−3 over 18∶2n−6 as substrate. The SO diet significantly increased 18∶3n−6, 20∶3n−6, and 22∶5n−6 in the liver and significantly decreased EPA and DHA. This indicates that desaturation enzymes were not specifically favoring n−3 over n−6 acids in perch lipid metabolism, and that these elongation and desaturation enzymes were influenced by n−3 and n−6 FA content in the diet. The present study indicates that high tissue content of DHA in the muscle of Eurasian perch was attributable to the greater ability for n−3 acid bioconversion.
Changes in lipid molecular species and sterols of microsomal membranes during aging of potato (Solanum tuberosum L.) seed‐tubers
Authors: Zabrouskov Vladimir , Knowles N. Richard
Published: November 2006

Changes in sterols and the molecular species composition of polar lipids from microsomal membranes were characterized as a prerequisite to determining how lipid chemistry affects membrane susceptibility to peroxidation during aging of potato tubers. Polar lipid content of the microsomal fraction fell 17% (protein basis) as tubers aged from 2 to 38 mon at 4°C. In younger seed‐tubers, PC concentration (protein basis) was the highest, followed by digalactosyldiacylglycerol (DGDG), PE, monogalactosyldiacylglycerol (MGDG), and PI. PC and PE increased 14 and 27%, respectively, whereas glycolipids fell 64 and PI 43% with advancing age. These changes resulted in PC and PE dominating the microsomal membrane lipids of 38‐mon‐old tubers. Nonpositional analysis of lipid molecular species across lipid pools showed an increase in 16∶0/18∶3, 18∶3/18∶3, and 18∶2/18∶3 (PC and PE only), and a decline in 18∶2/18∶2 and 16∶0/18∶2 (except for MGDG) with advancing tuber age. The increase in 18∶3‐bearing species effected a linear increase in double‐bond index (DBI) of PC and PE during aging. The DBI of DGDG did not change with age; however, it fell 65% for MGDG, resulting in an overall decrease in average microsomal DBI. In addition, Δ5‐avenasterol and stigmasterol concentrations increased 1.6‐ and 3.3‐fold, respectively, effecting a significant increase in the sterol/phospholipid ratio with advancing tuber age. The increase in sterol/phospholipid ratio and the possibility that the increased unsaturation of microsomal membranes reflects a compensatory response to maintain optimal membrane function in light of the age‐induced loss of galactolipid and PI are discussed.
Selective (R)‐3‐hydroxylation of FA by Stenotrophomonas maltophilia
Authors: Weil Kerstin , Gruber Patrick , Heckel Frank , Harmsen Dag , Schreier Peter
Published: November 2006

Soil samples were screened for microorganisms selectively transforming FA. One of the isolated strains was identified as the bacterium Stenotrophomonas maltophilia by its phenotypic features and genotypic characterization by sequencing the ribosomal RNA gene. Using linoleic acid as substrate resulted in the formation of two major compounds. After liquid chromatographic isolation and separation, their structures were elucidated by HPLC‐tandem MS, GC‐MS, and NMR techniques to be 3‐hydroxy‐Z6‐dodecenoic acid and 3‐hydroxy‐Z5, Z8‐tetradecadienoic acid. In additional experiments, other FA, such as α‐linolenic, oleic, palmitoleic, myristoleic, and cis‐vaccenic acids, were converted to 3‐hydroxylated metabolites of shorter chain lengths as well. Determination of the enantiomeric composition revealed highly enriched (R)‐hydroxylation (88–98% enantiomeric excess).
Saturated and unsaturated anteiso‐C19 acids in the seed lipids from Hesperopeuce mertensiana (Pinaceae)
Authors: Destaillats Frédéric , Wolff Robert L. , Angers Paul
Published: November 2006

Minor uncommon FA from Hesperopeuce mertensiana (a gymnosperm species of the Pinaceae family) seed oil were characterized through a combination of silver ion TLC of their FAME, and GLC coupled with MS of their picolinyl derivatives. These uncommon components have the structures 16‐methyloctadecanoic (anteiso‐19∶0), 16‐methyl‐cis‐9‐octadecenoic (anteiso‐19∶1), and 16‐methyl‐cis‐9,cis‐12‐octadecadienoic (anteiso‐19∶2) acids. These branched C19 acids were identified earlier in the wood of Picea abies, which would indicate that such acids could be widespread, though minor, components of Pinaceae lipids.