bluuebunny/crossref_metadata_2025 huggingface dataset:
Lipoproteins modify the macrophage uptake of triacylglycerol emulsion and of zymosan particles by similar mechanisms
Authors: Carvalho Márcia D. T. , Tobias Vanessa E. , Vendrame Célia M. V. , Shimabukuro Alice F. , Gidlund Magnus , Quintão Eder C. R.
Published: November 2006

The uptake of lipids and formation of foam cells are key events in atherosclerosis and in eruptive xanthomata formation in primary hyperchylomicronemia. Here we have compared the influence of low density lipoprotein (LDL), oxidized LDL (oxLDL), high density lipoprotein (HDL), and delipidated HDL (apoHDL) on the uptake by macrophages of zymosan (an insoluble fraction of yeast cell walls) and of triglyceride‐rich emulsion (EM) particles that resemble chylomicrons, but, like zymosan, are equally devoid of protein components. Zymosan internalization is known to occur through unspecific phagocytosis, whereas natural chylomicrons are taken up by several specific lipoprotein receptors. We found that phagocytosis is not promoted as much by oxLDL as by normal LDL. HDL‐coated zymosan was found to be inert and apoHDL slightly enhanced phagocytosis. LDL and apoHDL promoted the uptake of EM while oxLDL and HDL significantly inhibited the uptake. Therefore, the data support that HDL, and not apoHDL, particles inhibit EM uptake. We concluded that by using lipoprotein‐coated zymosan particles, we could demonstrate different biological effects of LDL, oxLDL, HDL, and apoHDL on macrophage phagocytosis and that this method could be useful to delineate components of the various lipoproteins important for the propagation or inhibition of the formation of foam cells.
Dietary docosahexaenoic acid suppresses inflammation and immunoresponses in contact hypersensitivity reaction in mice
Authors: Tomobe Yoko I. , Morizawa Kazuya , Tsuchida Mamoru , Hibino Hidehiko , Nakano Yoshio , Tanaka Yukihisa
Published: November 2006

This study was designed to examine the immunomodulatory effects of dietary docosahexaenoic acid (DHA) in the absence of eicosapentaenoic acid (EPA). We investigated the effects of feeding dietary DHA ethyl ester (DHA‐Et) (97% pure) at levels of 4.8 wt% of the total diet and of feeding EPA ethyl ester (EPA‐Et) (99% pure) at 4.8 wt% on the inflammatory response in the challenge phase of the contact hypersensitivity reaction (CHR) in the ears of mice sensitized with 2,4‐dinitro‐1‐fluorobenzene (DNFB). The effect of DHA‐Et on T lymphocytes at the CHR site was examined using anti‐CD4 antibodies. Furthermore, we examined the cytokines formed at the CHR site on the mRNA level. It was found that 24 h after the challenge, DHA‐Et but not EPA‐Et reduced the ear swelling. Infiltration of inflammatory cells, in particular, CD4‐positive T lymphocytes, into the ears in the challenge phase of CHR was observed. DHA‐Et reduced the infiltration of CD4‐positive T lymphocytes into the ears. DHA‐Et also decreased the expression of interferon‐γ, interleukin (IL)‐6, IL‐1β, and IL‐2 mRNA in ears. These observations suggest that DHA, but not EPA, may exert an antiinflammatory and immunosuppressive effect. The immunosuppressive effectiveness of fish oil may be attributed mainly to DHA.
Effects of different medium‐chain fatty acids on intestinal absorption of structured triacylglycerols
Authors: Mu Huiling , Høy Carl‐Erik
Published: November 2006

To study the effect of the chain length of medium‐chain fatty acids on the intestinal absorption of long‐chain fatty acids, we examined the lymphatic transport of fat following administration of five purified structured triacylglycerols (STAG) containing different medium‐chain fatty acids in the sn‐1, 3 positions and long‐chain fatty acids in the sn‐2 position in a rat model. Significant amounts of medium‐chain fatty acids were found in lymph samples after intragastric administration of 1,3‐dioctanoyl‐2‐linoleyl‐sn‐glycerol (8∶0/18∶2/8∶0), 1,3‐didecanoyl‐2‐linoleyl‐sn‐glycerol, and 1,3‐didodecanoyl‐2‐linoleyl‐sn‐glycerol. The accumulated lymphatic transport of medium‐chain fatty acids increased with increasing carbon chain length. The recoveries of caprylic acid (8∶0), capric acid (10∶0), and lauric acid (12∶0) were 7.3±0.9, 26.3±2.4, and 81.7±6.9%, respectively. No significant differences were observed for the maximal intestinal absorption of linoleic acid (18∶2n−6) when the chain length of medium‐chain fatty acids at the primary positions was varied, and the absorption of 18∶2 and oleic acid (18∶1) from 8∶0/18∶2/8∶0 and 1,3‐dioctanoyl‐2‐oleyl‐sn‐glycerol was similar. We conclude that the chain length of the medium‐chain fatty acids in the primary positions of STAG does not affect the maximal intestinal absorption of long‐chain fatty acids in the sn‐2 position in the applied rat model, whereas the distribution of fatty acids between the lymphatics and the portal vein reflects the chain length of the fatty acids.
Breast‐fed infants achieve a higher rate of brain and whole body docosahexaenoate accumulation than formula‐fed infants not consuming dietary docosahexaenoate
Authors: Cunnane Stephen C. , Francescutti Valerie , Brenna J. Thomas , Crawford Michael A.
Published: November 2006

Docosahexaenoate (DHA) has been increasingly recognized as an important fatty acid for neural and visual development during the first 6 mon of life. One important point of controversy that remains is the degree to which adequate levels of DHA can be acquired from endogenous synthesis in infants vs. what should be provided as dietary DHA. We have approached this problem by a retrospective analysis of published body composition data to estimate the actual accumulation of DHA in the human infant brain, liver, adipose tissue, remaining lean tissue, and whole body. Estimating whether infants can synthesize sufficient DHA required comparison to and extrapolation from animal data. Over the first 6 mon of life, DHA accumulates at about 10 mg/d in the whole body of breast‐fed infants, with 48% of that amount appearing in the brain. To achieve that rate of accumulation, breast‐fed infants need to consume a minimum of 20 mg DHA/d. Virtually all breast milk provides a DHA intake of at least 60 mg/d. Despite a store of about 1,050 mg of DHA in body fat at term birth and an intake of about 390 mg/d α‐linolenate (α‐LnA), the brain of formula‐fed infants not consuming DHA accumulates half the DHA of the brain of breast‐fed infants while the rest of the body actually loses DHA over the first 6 mon of life. No experimental data indicate that formula‐fed infants not consuming DHA are able to convert the necessary 5.2% of α‐LnA intake to DHA to match the DHA accumulation of breast‐fed infants. We conclude that dietary DHA should likely be provided during at least the first 6 mon of life.
Biochemical modifications and transcriptional alterations attendant to sterol feeding in Phytophthora parasitica
Authors: Dotson W. David , Tove Shirley R. , Parks Leo W.
Published: November 2006

Phytophthora species are eukaryotic sterol auxotrophs that possess the ability to grow, albeit poorly, in the complete absence of sterols. Growth of Phytophthora is often improved substantially when an exogenous source of sterol is provided. Additionally, sterols may be required for sexual and asexual sporulation in Phytophthora. Our research has been focused on identifying and characterizing the immediate physiological effects following sterol addition to cultures of P. parasitica. Through gas chromatographic analysis of extracts from P. parasitica cultures that were fed various sterols, we have ob‐tained evidence for sterol C5 desaturase and Δ7 reductase activities in this organism. Zoo blots were probed with DNA sequences encoding these enzymes, from Saccharomyces cerevisiae and Arabidopsis thaliana. Hybridization of a S. cerevisiae ERG3 probe to P. parasitica DNA was observed, implicating sequence similarity between the sterol C5 desaturase encoding genes. Differential display experiments, using RNA from P. parasitica, have demonstrated a pattern of altered gene expression between cultures grown in the presence and absence of sitosterol. Characterization of sterol‐related metabolic effects and sterol functions in Phytophthora should lead to improved measures for control of this important group of plant pathogens.
Design and synthesis of new steroidal inhibitors of estrogen synthase (aromatase)
Authors: Parish Edward J. , Li Shengrong , Rao Zhigang
Published: November 2006

The estrogen synthase (aromatase) enzyme system is responsible for the biosynthesis of estrogen hormones in human females. Estrogens are vital for normal growth and development, but will promote the growth of certain breast cancers. Appromaximately 30–50% of breast cancers are considered to be hormone‐dependent. Consequently regulation of estrogen biosynthesis has advanced as a potential therapeutic strategy. This has led to the development of active‐site inhibitors, which may have potential for the control of breast cancer. We have recently prepared a number of new steroidal inhibitors that have been evaluated as aromatase inhibitors. These include steroidal A/B‐ring isoxazoles and a series of A/B‐ring pyrazoles with alkyl‐ and aryl‐substituted nitrogen. In addition, we have developed new chemical procedures for the synthesis of 6β‐hydroxy steroids, which could be key intermediates in the preparation of C‐19 inhibitors of aromatase activity.
Cholesterol synthesis in the vertebrate retina: Effects of U18666A on rat retinal structure, photoreceptor membrane assembly, and sterol metabolism and composition
Authors: Fliesler S. J. , Richards M. J. , Miller C. ‐Y. , Cenedella R. J.
Published: November 2006

Treatment of neonatal rats with U18666A, an inhibitor of desmosterol Δ24‐reductase, results in accumulation of desmosterol (Δ5,24) and depletion of cholesterol (Δ5) in various bodily tissues and also causes cataracts. We evaluated the effects of U18666A on the sterol composition, de novo sterol synthesis, and histological structure of the retina. Neonatal Sprague‐Dawley rats were injected subcutaneously with U18666A (15 mg/kg, in olive oil) every other day from birth through 3 wk of age; in parallel, control rats received olive oil alone. At 21 d, treated and control groups each were subdivided into two groups: one group of each was injected intravitreally with [3H]acetate; retinas were removed 20 h later and non‐saponifiable lipids (NSL) were analyzed by radio‐high‐performance liquid chromatography. The other group was injected intravitreally with [3H]leucine; 4 d later, one eye of each animal was evaluated by light and electron microscopy and light microscopic autoradiography, while contralateral retinas and rod outer segment (ROS) membranes prepared thereform were analyzed by sodium dodecyl sulfate‐polyacrylamide gel electrophoresis/fluorography. In the treated group, the Δ5/Δ5,24 mole ratio of retinas was ca. 1.0, and >88% of the NSL radioactivity was in Δ5,24; in contrast, control retinas had Δ5/Δ5,24 >170, with >80% of the NSL radioactivity in Δ5. Retinal histology, ultrastructure, ROS renewal rates, and rhodopsin synthesis and intracellular trafficking were comparable in both treated and control animals. These results suggest that desmosterol can either substitute functionally for cholesterol in the retina or it can complement subthreshold levels of cholesterol by sterol synergism.
Rationally designed inhibitors as tools for comparing the mechanism of squalene‐hopene cyclase with oxidosqualene cyclase
Authors: Viola Franca , Ceruti Maurizio , Cattel Luigi , Milla Paola , Poralla Karl , Balliano Gianni
Published: November 2006

The inhibition of squalene‐hopene cyclase (SHC) (E.C. 5.4.99.‐), an enzyme of bacterial membranes catalyzing the formation of pentacyclic sterol‐like triterpenes, was studied by using different classes of compounds originally developed as inhibitors of oxidosqualene cyclase (OCS) (E.C. 5.4.99.7), the enzyme of eukaryotes responsible for the formation of tetracyclic precursors of sterols. The mechanism of cyclization of squalene by SHC, beginning with a protonation of the 2,3 double bond by an acidic residue of the enzyme, followed by a series of electrophilic additions of the carbocationic intermediates to the double bonds, is similar to the mechanism of cyclization of 2,3‐oxidosqualene by OSC. The inhibitors studied included: (i) analogs of the carbocationic intermediates formed during cyclization, such as aza‐analogs of squalene and 2,3‐oxidosqualene; (ii) affinity‐labeling inhibitors bearing a methylidene reactive group; and (iii) vinyldioxidosqualenes and vinylsulfide derivatives of the substrates. Comparison of the results obtained with the two enzymes, SHC and OSC, showed that many of the most effective inhibitors of OSC were also able to inhibit SHC, while some derivatives acted as specific inhibitors. Differences could be easily explained on the basis of the different substrate specificity of the two enzymes.
Structure‐apoptotic potency evaluations of novel sterols using human leukemic cells
Authors: Johnson Betty H. , Russell Michael J. , Krylov Alexander S. , Medh Rheem D. , Ayala‐Torres Sylvette , Regner Justin Lee , Thompson E. Brad
Published: November 2006

Three oxidized analogs of cholesterol have been characterized for their ability to cause apoptotic cell death in CEM‐C7‐14 human leukemic cells. In addition to testing 15‐ketocholestenol (K15), 15‐ketocholestenol hydroxyethyl ether (CK15), and 7‐ketocholesterol hydroxyethyl ether (CK7), an oxysterol of known apoptotic response, 25‐hydroxycholesterol (25OHC), served as a standard for comparison. Growth studies based on dye exclusion by viable cells while using a sublethal concentration of oxysterols ranked their potency for cell kill as 25OHC>K15>CK15>CK7. Both the TUNEL assay (terminal deoxynucleotidyl transferase‐mediated dUTP‐X nick end labeling), which quantifies the amount of DNA nicks caused by a toxic agent, and the MTT assay, which measures cell metabolism and thus reflects cell viability, substantiated the same rank order. An ELISA assay for evaluating release of DNA fragments into the cytosol after treatment gave a similar potency order. The oncogene c‐myc mRNA was suppressed by all three oxysterols. with 25OHC and K15 being the most potent suppressors. Hoechst and Annexin V staining documented that these oxysterols kill cells by an apoptotic pathway as evidenced by condensation of nuclear chromatin and plasma membrane inversion, respectively. From these in vitro studies, we believe that 25OHC, K15, and possibly CK15 have the potential to be chemotherapeutic agents.
C27 to C32 sterols found in Pneumocystis, and opportunistic pathogen of immunocompromised mammals
Authors: Kaneshiro Edna S. , Wyder Michael A.
Published: November 2006

Pneumocystis carinii is the paradigm of opportunistic infections in immunocompromised mammals. Prior to the acquired immunodeficiency syndrome (AIDS) pandemic and the use of immunosuppressive therapy in organ transplant and cancer patients, P. carinii was regarded as a curiosity, rarely observed clinically. Interest in this organism exploded when it was identified as the agent of P. carinii pneumonia (PcP), the direct cause of death among many AIDS patients. Aggressive prophylaxis has decreased the number of acute PcP cases, but it remains among the most prevalent opportunistic infections found within this patient population. The taxonomic assignment of P. carinii has long been argued; molecular genetics data now demonstrate that it is a fungus. Several antimycotic drugs are targeted against ergosterol or its biosynthesis, but these are not as effective against PcP as they are against other fungal infections. This can now be explained in part by the identification of the sterols of P. carinii. The organism lacks ergosterol but contains distinct C28 and C29 Δ7 24‐alkylsterols. Also, 24‐methylenelanost‐8‐en‐3β‐ol (C31) and pneumocysterol, (24Z)‐ethylidenelanost‐8‐en‐3β‐ol (C32) were recently identified in organisms infecting humans. Together, the Δ7 24‐alkylsterols and pneumocysterol are regarded as signature lipids of the pathogen that can be useful for the diagnosis of PcP, since no other lung pathogen is known to contain them. Cholesterol (C27), the dominant sterol component in P. carinii, is probably totally scavenged from the host. De novo synthesis of sterols has been demonstrated by the presence of lovastatin‐sensitive 3‐hydroxy‐3‐methylglutaryl‐CoA reductase activity, the incorporation of radiolabeled mevalonate and squalene into P. carinii sterols, and the reduction in cellular ATP in cells treated with inhibitors of enzymes in sterol biosynthesis.
Plasma oxysterols and tocopherol in patients with diabetes mellitus and hyperlipidemia
Authors: Murakami Hiroshi , Tamasawa Naoki , Matsui Jun , Yasujima Minoru , Suda Toshihiro
Published: November 2006

The plasma levels of free oxysterols (7‐ketocholesterol: 7α‐hydroxy‐, 7β‐hydroxy‐, 25‐hydroxy‐, and 27‐hydroxycholesterol; and 5α,6α‐epoxycholestanol) in patients with diabetes mellitus and hypercholesterolemia were determined using gas chromatography‐mass spectrometry with selective ion monitoring. We studied 39 patients with diabetes mellitus, 20 nondiabetic patients with hypercholesterolemia, and 37 normal controls. Plasma cholesterol levels in diabetic and hypercholesterolemic patients showed no statistical difference. Plasma 7‐ketocholesterol was significantly higher in patients with diabetes (31.6±2.8 ng/mL) or hypercholesterolemia (52.3±5.9) than in the control group (22.4±1.2). The increased plasma cholesterol can be regarded as an oxidation substrate for the oxidant stress and the higher absolute levels of oxysterols in hypercholesterolemic plasma compared with the control plasma. This difference disappeared when 7‐ketocholesterol was expressed in proportion to total cholesterol. The oxidizability of plasma cholesterol was evaluated by comparing the increased ratio of 7‐ketocholesterol after CuSO4 oxidation to the ratio before. We demonstrated that the patients with diabetes showed increased oxidizability (77.5%) compared with the control (36.6%) or hyperlipemic group (45.3%), which is likely due to the lower amounts of α‐tocopherol in the diabetics. Measurement of oxysterols may serve as a marker for in vivo oxidized lipoproteins in diabetes and hyperlipemia.
Use of a 13C tracer to quantify the plasma appearance of a physiological dose of lutein in humans
Authors: Yao Lihang , Liang Yuexia , Trahanovsky Walter S. , Serfass Robert E. , White Wendy S.
Published: November 2006

Increased intake of lutein from vegetables promotes increased density of the macular pigment and therefore may protect against age‐related macular degeneration. Our objective was to use a 13C tracer and high‐precision gas chromatography‐combustion interfaced‐isotope ratio mass spectrometry (GC‐C‐IRMS) to investigate metabolism of a lutein dose equivalent to that absorbed from vegetables. Biosynthetic per‐labeled (>99% 13C) lutein was purified from a commercially available extract of algal biomass. Subjects (n=4) ingested 3 mg of [13C]lutein with a standardized low‐carotenoid breakfast. Blood samples were collected at baseline and then hourly for 12 h; additional blood samples were drawn at 16, 24, 48, 72, 96, 192, 360, and 528 h. To produce perhydro‐β‐carotene suitable for analysis by GC‐C‐IRMS, the plasma lutein fraction was hydrogenated on palladium‐on‐carbon catalyst with acid‐catalyzed hydrogenolysis. The stable carbon isotope (13C/12C) ratio measured by GC‐C‐IRMS was used to calculate the plasma concentration of [13C]lutein. There was a rapid increase in [13C]lutein in plasma until peak enrichment at 16 h followed by a decline to the next measurement at 24 h. At 528 h, small changes in 13C enrichment from baseline could still be measured in plasma lutein. High‐precision GC‐C‐IRMS enables complete definition of the appearance and disappearance of [13C]lutein in plasma after ingestion of a dose similar to that absorbed from foods.
Membrane physical properties do not explain increased cyclic AMP production in hepatocytes from rats fed menhaden oil
Authors: Bizeau Michael E. , Hazel Jeffrey R.
Published: November 2006

To study the effect of altering plasma membrane fatty acid composition on the glucagon signal transduction pathway, cAMP accumulation was measured in hepatocytes from rats fed diets containing either menhaden oil (MO) or coconut oil (CO). Hepatocytes from MO‐fed animals produced significantly more cAMP in response to glucagon and forskolin compared to CO‐fed animals. Glucagon receptor number and affinity were similar in MO‐ and CO‐fed rats. Liver plasma membranes from MO‐fed animals were enriched in long‐chain n‐3 fatty acids and contained significantly lower amounts of saturated C10−C16 and 18∶1n−9 than CO‐fed animals. Membrane physical properties were examined using both Fourier transform infrared spectroscopy (FTIR) and the fluorescent probe 1,6‐diphenyl‐1,3,5‐hexatriene (DPH). FTIR analysis revealed that below 34°C, CO membranes were more ordered than MO membranes. However, as assay temperature approached 37°C, MO and CO membranes became similarly ordered. DPH polarization values indicated no differences in membrane order at 37°C, whereas membrane order was decreased in CO‐fed animals at 25°C. These data indicate the importance of assay temperature in assessing the influence of membrane physical properties on the activity of signal transduction pathways. Whereas increased signal transduction activity has been correlated to reduced membrane order in MO‐fed animals, these data indicate that at physiological temperatures membrane order did not vary between groups. Enhanced cAMP accumulation in response to forskolin indicates that adenylate cyclase activity or content may be elevated in MO‐vs. CO‐fed rats. Enhanced adenylate cyclase activity may result, in part, from changes in specific fatty acids in hepatocyte plasma membranes without demonstrable changes in membrane physical properties.
Dietary cod liver oil decreases arachidonic acid in rat gastric mucosa and increases stress‐induced gastric erosions
Authors: Olafsson Sigurdur Oli , Hallgrimsson Jonas , Gudbjarnason Sigmundur
Published: November 2006

The purpose of this study was to examine the influence of long‐term feeding of dietary fat rich in either n−3 or n−6 fatty acids on the availability of arachidonic acid (20∶4n−6) in major phospholipids of gastric mucosa in rats. Three groups of male Wistar rats were fed either a standard diet, a cod liver oil‐enriched diet (10% by weight), or a corn oil‐enriched diet (10% by weight) for 8 mon. Dietary cod liver oil significantly reduced the level of 20∶4n−6 in phosphatidylcholine (PC) and in phosphatidylethanolamine (PE) of gastric mucosa. The loss of 20∶4n−6 was compensated for by eicosapentaenoic acid (20∶5n−3) in PC, whereas the decrease in 20∶4n−6 in PE corresponded to the increase in three n−3 fatty acids: 20∶5n−3, docosapentaenoic acid (22∶5n−3), and docosahexaenoic acid (22∶6n−3). The level of 20∶5n−3 was higher than the level of 22∶6n−3 both in PC and PE of mucosa in rats fed cod liver oil. Diets supplemented with corn oil increased the level of 18∶2n−6 but decreased the monoene fatty acids 16∶1 and 18∶1n−7 in PC but not in PE of gastric mucosa. The 20∶4n−6 levels of both PC and PE were markedly reduced by dietary cod liver oil, to about one‐third of control levels. Similar changes were also observed in the stomach wall. Gastric erosions were observed in all rats exposed to restriction stress, but this form of stress induced twice the number of erosions in rats fed fish oil compared to control rats or rats fed corn oil. We conclude that a diet rich in fish oil altered the balance between n−6 and n−3 fatty acids in major gastric mucosal phospholipids, markedly reduced the availability of 20∶4n−6, and increased the incidence of gastric erosions induced by restriction or emotional stress.
Low erucic acid canola oil does not induce heart triglyceride accumulation in neonatal pigs fed formula
Authors: Green Timothy J. , Innis Sheila M.
Published: November 2006

Canola oil is not approved for use in infant formula largely because of concerns over possible accumulation of triglyceride in heart as a result of the small amounts of erucic acid (22∶1n−9) in the oil. Therefore, the concentration and composition of heart triglyceride were determined in piglets fed from birth for 10 (n=4–6) or 18 (n=6) d with formula containing about 50% energy fat as 100% canola oil (0.5% 22∶1n−9) or 100% soybean oil, or 26% canola oil or soy oil (blend) with palm, high‐oleic sunflower and coconut oil, providing amounts of 16∶0 and 18∶1 closer to milk, or a mix of soy, high‐oleic sunflower and flaxseed oils with C16 and C18 fatty acids similar to canola oil but without 22∶1. Biochemical analysis found no differences in heart triglyceride concentrations among the groups at 10 or 18 d. Assessment of heart triglycerides using Oil Red O staining in select treatments confirmed no differences between 10‐d‐old piglets fed formula with 100% canola oil (n=4), 100% soy oil (n=4), or the soy oil blend (n=2). Levels of 22∶1n−9 in heart triglyceride and phospholipid, however, were higher (P<0.01) in piglets fed 100% canola oil or the canola oil blend, with higher levels found in triglycerides compared with phospholipids. The modest accumulation of 22∶1n−9 associated with feeding canola oil was not associated with biochemical evidence of heart triglyceride accumulation at 10 and 18 d.
Dehydroepiandrosterone alters lipid profiles in Zucker rats
Authors: Abadie Jude M. , Malcom Gray T. , Porter Johnny R. , Svec Frank
Published: November 2006

High free fatty acid (FFA) levels are common in obesity and in diseases such as diabetes that are associated with the obese state. Dehydroepiandrosterone (DHEA) decreases dietary fat consumption, body fat content, and insulin levels in the obese Zucker rat (ZR), a genetic model of human youth‐onset obesity and type 2 diabetes mellitus. This study was conducted to investigate the effects of DHEA on lean and obese ZR serum, adipose, and hepatic tissue fatty acid (FA) profiles and serum FFA levels. Because DHEA is known to decrease fat consumption and body fat, we postulate that DHEA may also alter FA profiles and FFA levels of the obese ZR such that they more closely resemble the profiles and levels of their lean siblings. In this study there was a DHEA and a pair‐fed (PF) group (n=6) for 12 lean and 12 obese ZR. The diet of the treatment groups was supplemented with 0.6% DHEA, and PF groups were given the same average calories consumed by their corresponding DHEA group for 30 d. Fasted animals were sacrificed, and FA profiles and FFA levels were measured. Serum FFA levels were higher in obese (∼1 mmol/L) compared to lean rats (∼0.6 mmol/L). After 30 d of DHEA treatment, FFA levels were lower (P<0.05) in both lean and obese groups. Although several significant differences in FA profile of serum, hepatic, and adipose lipid components were observed between lean and obese ZR, DHEA‐related changes were only observed in the serum phospholipid (PL) and liver PL and triglyceride fractions. The slight but significant decrease in serum FFA levels may be reflected by changes in serum PL FA profiles. Specific hepatic FA profile alterations may be related to DHEA's known effects in inducing hepatic peroxisomes. We speculate that such FA changes may give insight into a mechanism for the action of DHEA.
Protective effect of olive oil and its phenolic compounds against low density lipoprotein oxidation
Authors: Fitó Montserrat , Covas María Isabel , Lamuela‐Raventós Rosa M. , Vila Joan , Torrents Jaume , de la Torre Carmen , Marrugat Jaume
Published: November 2006

The protective effect of phenolic compounds from an olive oil extract, and of olive oils with (extra‐virgin) and without (refined) phenolic components, on low density lipoprotein (LDL) oxidation was investigated. When added to isolated LDL, phenolics [0.025–0.3 mg/L caffeic acid equivalents (CAE)] increased the lag time of conjugated diene formation after copper‐mediated LDL oxidation in a concentration‐dependent manner. Concentrations of phenolics greater than 20 mg/L inhibited formation of thiobarbituric‐acid reactive substances after AAPH‐initiated LDL oxidation. LDL isolated from plasma after preincubation with phenolics (25–160 mg/L CAE) showed a concentration‐dependent increase in the lag time of conjugated diene formation after copper‐mediated LDL oxidation. Refined olive oil (0 mg/L CAE) and extra‐virgin olive oil (0.1 and 0.3 mg/L CAE) added to isolated LDL caused an increase in the lag time of conjugated diene formation after copper‐mediated LDL oxidation that was related to olive oil phenolic content. Multiple regression analysis showed that phenolics were significantly associated with the increase in lag time after adjustment for effects of other antioxidants; α‐tocopherol also achieved a statistically significant effect. These results indicate that olive oil phenolic compounds protect LDL against peroxyl radical‐dependent and metal‐induced oxidation in vitro and could associate with LDL after their incubation with plasma. Both types of olive oil protect LDL from oxidation. Olive oil containing phenolics, however, shows more antioxidant effect on LDL oxidation than refined olive oil.
Composition of cecal bile acids in ex‐germfree mice inoculated with human intestinal bacteria
Authors: Narushima Seiko , Iton Kikuji , Kuruma Kazuo , Uchida Kiyohisa
Published: November 2006

Germfree (GF) mice were orally inoculated with human fecal suspension or various components of human fecal microbiota. Three weeks after the inoculation, cecal bile acid composition of these mice was examined. More than 80% of total bile acids was deconjugated in the cecal contents of ex‐GF mice associated with human fecal dilutions of 10−2 or 10−6, or anaerobic growth from a dilution of 10−6. In these ex‐GF mice, deoxycholic acid accounted for about 20% of total bile acids. In the cecal contents of ex‐GF mice associated only with clostridia, unconjugated bile acids made up less than 40% of total bile acids, about half of those in other ex‐GF groups. However, the percentage of deoxycholic acid in these mice was the same as that in the other groups. These results indicate that dominant anaerobic bacterial combination is efficient for deconjugation of primary bile acids, and that clostridia in the human feces may play an important role in 7α‐dehydroxylation of unconjugated primary bile acids in the intestine.
Lipid and fatty acid composition and energy partitioning during embryo development in the shrimp Macrobrachium borellii
Authors: Heras Horacio , Gonzalez‐Baró M. R. , Pollero Ricardo J.
Published: November 2006

Energy partitioning, composition of lipids and fatty acids, and their utilization by embryos were determined in the lecithotrophic shrimp Macrobrachium borellii during seven development stages. The biochemical composition at stage I is represented by lipids, proteins, and carbohydrates, with 29.3, 28.7, and 0.2% dry weight, respectively. The former two were identified as the major energy‐providing components, contributing 131 and 60 cal/100 mg egg, dry weight, respectively. The overall conversion efficiency (CE) was 45.0% (calculated as percentage of vitelline energy transformed into embryonic tissues). Lipids were the most important energy reserve (CE 39.3%), followed by proteins (CE 57.1%), both being simultaneously utilized during development while carbohydrates were synthesized de novo (CE 587.5%). Variation in the lipid class composition of embryos and vitellus showed an accumulation of triacylglycerols (TAG) and phospholipids (PL) up to stage IV, a more active accumulation and selective utilization phase (stages V and VI), and a consumption and de novo synthesis period until hatching. Structural lipids (PL and cholesterol) and pigment astaxanthin were selectively conserved in embryos, but TAG, hydrocarbons, and esterified sterols were preferentially depleted. Monounsaturated fatty acids (FA) were the major group in TAG, whereas polyunsaturated FA (PUFA) were the major group in PL after organogenesis. Certain PUFA such as 22∶6n−3 and 20∶5n−3 were selectively accumulated in PL.
Evidence for the presence of 1,2‐cyclic acetal type sn‐glycero‐3‐phosphoethanolamines in the sea anemone, Actiniogeton sp.
Authors: Tanaka Ryuichiro , Ishizaki Hiroaki , Morita Takahiro , Miyahara Kazumoto , Noda Naoki
Published: November 2006

Five 1,2‐cyclic acetal‐type sn‐glycero‐3‐phosphoethanolamines (CGPE) were isolated in a pure state from the sea anemone, Actiniogeton sp. (Coelenterata). Their structures, including the absolute configurations, have been determined on the basis of chemical and spectral data to be so‐called Feulgen's acetalphosphatides, which have been regarded as artifacts derived from original plasmalogens. We examined whether these CGPE are intact constitutents in the animal tissues and obtained reliable confirmation that CGPE are normally present in the sea anemone.
Lipid analog with 2‐nitrophenol trigger designed for liposome fusion at physiological pH
Authors: Shah S. N. , Tomohiro Takenori , Ogawa Yoshikatsu , Kodaka Masato , Okuno Hiroaki
Published: November 2006

A novel lipid analog with two long alkyl (C16) chains, an aspartate skeleton, a connecting alkyl (C8) chain, and 2‐nitrophenol trigger group is synthesized by an efficient synthetic route, which can induce liposome fusion at physiological pH.
Smoking influences the association between apolipoprotein E and lipids: The national heart, lung, and blood institute family heart study
Authors: Djoussé Luc , Myers Richard H. , Coon Hilary , Arnett Donna K. , Province Michael A. , Ellison R. Curtis
Published: November 2006

Apolipoprotein E allele 4 (apo ɛ4) and smoking each have been associated with an unfavorable lipid profile. We used data collected on 1,472 subjects in the National Heart, Lung, and Blood Institute Family Heart Study to assess whether smoking interacts with apo ɛ4 to influence the levels of plasma lipids. We dichotomized smoking and apo ɛ4 and used analysis of covariance to estimate the means of lipids. Smokers had lower body mass index, were younger, and consumed less fruits and vegetables. Among individuals without apo ɛ4, comparing nonsmokers with smokers, mean low density lipoprotein cholesterol (LDL) was 129.3 and 134.4 mg/dL, respectively, for women and 126.1 and 127.6 mg/dL, respectively, for men. Among subjects with an apo ɛ4 allele, corresponding means were 132.0, and 152.9 mg/dL, respectively, for women and 131.3 and 137.3 mg/dL, respectively, for men (P for interaction <0.001 for women and 0.11 for men). A similar interaction was observed for total cholesterol among women (P=0.02). This study shows a statistically significant effect modification of the relation of apo ɛ4 to LDL and total cholesterol by smoking among women. Smoking may enhance genetic susceptibility to an unfavorable lipid profile among subjects with apo ɛ4.
Electrospray ionization mass spectrometric analyses of changes in tissue phospholipid molecular species during the evolution of hyperlipidemia and hyperglycemia in Zucker diabetic fatty rats
Authors: Hsu Fong‐Fu , Bohrer Alan , Wohltmann Mary , Ramanadham Sasanka , Ma Zhongmin , Yarasheski Kevin , Turk John
Published: November 2006

The Zucker diabetic fatty (ZDF) rat is a genetic model of type II diabetes mellitus in which males homozygous for nonfunctional leptin receptors (fa/fa) develop obesity, hyperlipidemia, and hyperglycemia, but rats homozygous for normal receptors (+/+) remain lean and normoglycemic. Insulin resistance develops in young fa/fa rats and is followed by evolution of an insulin secretory defect that triggers hyperglycemia. Because insulin secretion and insulin sensitivity are affected by membrane phospholipid fatty acid composition, we have determined whether metabolic abnormalities in fa/fa rats are associated with changes in tissue phospholipids. Electrospray ionization mass spectrometric analyses of glycerophosphocholine (GPC) and glycerophosphoethanolamine (GPE) molecular species from tissues of prediabetic (6 wk of age) and overtly diabetic (12 wk) fa/fa rats and from +/+ rats of the same ages indicate that arachidonate‐containing species from heart, aorta, and liver of prediabetic fa/fa rats made a smaller contribution to GPC total ion current than was the case for +/+ rats. There was a correspondingly larger contribution from species with sn‐2 oleate or linoleate substituents in fa/fa heart and aorta. The relative contributions of arachidonate‐containing GPC species increased in these tissues as fa/fa rats aged and were equal to or greater than those for +/+ rats by 12 wk. For heart and aorta, relative contributions from GPE species with sn‐2 arachidonate or docosahexaenoate substituents to the total ion current increased and those from species with sn‐2 oleate or linoleate substituents fell as fa/fa rats aged, but these tissue lipid profiles changed little with age in +/+ rats. GPC and GPE profiles for brain, kidney, sciatic nerve, and red blood cells were similar among fa/fa and +/+ rats at 6 and 12 wk or age, and pancreatic islets from fa/fa and +/+ rats exhibited similar GPC and GPE profiles at 12 wk of age. Under‐representation of arachidonate‐containing GPC and GPE species in some fa/fa rat tissues at 6 wk could contribute to insulin resistance, but depletion of islet arachidonate‐containing GPC and GPE species is unlikely to explain the evolution of the insulin secretory defect that is well‐developed by 12 wk of age.
Triacylglycerols of the red microalga Porphyridium cruentum can contribute to the biosynthesis of eukaryotic galactolipids
Authors: Khozin‐Goldberg Inna , Yu Hu Zheng , Adlerstein Daniel , Didi‐Cohen Shoshana , Heimer Yair M , Cohen Zvi
Published: November 2006

A mutant of the red microalga Porphyridium cruentum was selected on the basis of impaired growth at suboptimal temperatures (15 vs. 25°C). Fatty acid and lipid analyses revealed diminished proportions of eicosapentaenoic acid (from 41 to 30%) and of the eukaryotic molecular species (from 38 to 28% of monogalactosyldiacylglycerol (MGDG) and elevated proportion (10 vs. 2%) of triacylglycerols (TAG) in the mutant, as compared with the wild type. Pulse labeling of the wild type cells with radioactive fatty acid precursors indicated an initial incorporation of the fatty acids into phosphatidylcholine (PC) and TAG. Following the pulse, the label of PC and TAG decreased with time (from 25 to 5% of the total dpm in TAG) while that of chloroplastic polar lipids, mainly MGDG, continued to increase. In the mutant, however, the labeling of TAG after the pulse was higher (30% of the total dpm) than that of the wild type and decreased only slightly to 20%. This may indicate that in P. cruentum, TAG can contribute to the biosynthesis of eukaryotic species of MGDG.
Intravenously injected [1‐14C]arachidonic acid targets phospholipids, and [1‐14C]palmitic acid targets neutral lipids in hearts of awake rats
Authors: Murphy Eric J. , Rosenberger Thad A. , Patrick Casey B. , Rapoport Stanley I.
Published: November 2006

The differential uptake and targeting of intravenously infused [1‐14C]palmitic ([1‐14C] 16∶0) and [1‐14C]arachidonic ([1‐14C]20∶4n−6) acids into heart lipid pools were determined in awake adult male rats. The fatty acid tracers were infused (170 μCi/kg) through the femoral vein at a constant rate of 0.4 mL/min over 5 min. At 10 min postinfusion, the rats were killed using pentobarbital. The hearts were rapidly removed, washed free of exogenous blood, and frozen in dry ice. Arterial blood was withdrawn over the course of the experiment to determine plasma radiotracer levels. Lipids were extracted from heart tissue using a two‐phase system, and total radioactivity was measured in the nonvolatile aqueous and organic fractions. Both fatty acid tracers had similar plasma curves, but were differentially distributed into heart lipid compartments. The extent of [1‐14C]20∶4n−6 esterification into heart phospholipids, primarily choline glycerophospholipids, was elevated 3.5‐fold compared to [1‐14C]16∶0. The unilateral incorporation coefficient, k*, which represents tissue radioactivity divided by the integrated plasma radioactivity for heart phospholipid, was sevenfold greater for [1‐14C]20∶4n−6 than for [1‐14C]16∶0. In contrast, [1‐14C]16∶0 was esterified mainly into heart neutral lipids, primarily triacylglycerols (TG), and was also found in the nonvolatile aqueous compartment. Thus, in rat heart, [1‐14C]20∶4n−6 was primarily targeted for esterification into phospholipids, while [1‐14C]16∶0 was targeted for esterification into TG or metabolized into nonvolatile aqueous components.
Incorporation and metabolism of trans 20∶5 in endothelial cells. Effect on prostacyclin synthesis
Authors: Loï C. , Chardigny J. M. , Cordelet C. , Leclere L. , Genty M. , Ginies C. , Noel J. P. , Sébédio J. L.
Published: November 2006

To study the ability of long‐chain trans fatty acids (FA) to be incorporated and metabolized into endothelial cells, bovine aortic endothelial cells were incubated with medium enriched eicosapentaenoic acid (EPA) bound to albumin (M2) or one of its geometrical isomers: 20∶5 5c,8c,11t,14c,17c(M3), 20∶5 5c,8c,11c,14c,17t(M4), or 20∶5 5c,8c,11t,14c,17t(M5). After 48 h of incubation, supernatant and cells were harvested and their lipids were analyzed, including prostacyclin synthesis. EPA and 22∶5n−3 of endothelial cells incubated with M2 were, respectively, three and two times higher than in control cells (incubated in M1, without any fatty acid added), whereas 22∶6n−3 increased only in the supernatant, suggesting its release after biosynthesis. However, 18∶2n−6 and 22∶4n−6 decreased (about 30%). Trans 20∶5 isomers represented 4.7, 3.9, and 5.2% of total phospholipid FA in endothelial cells incubated with M3, M4, and M5, respectively. They were elongated into trans 22∶5 and trans 24∶5, as revealed by gas chromatography‐mass spectrometry and gas chromatography‐Fourier transform infrared analysis. In cells incubated with M2, M3, M4, and M5, prostacyclin synthesis was inhibited by 49.0, 62.5, 60.5, and 72.0%, respectively. This effect may be due to less available arachidonic acid in the cells and to a competition between EPA isomers and AA at the level of cyclooxygenase pathway, as it was demonstrated that 20∶5 Δ17t was metabolized by this enzyme.
Fetal erythrocyte phospholipid polyunsaturated fatty acids are altered in pregnancy complicated with gestational diabetes mellitus
Authors: Wijendran Vasuki , Bendel Robert B. , Couch Sarah C. , Philipson Elliot H. , Cheruku Sunita , Lammi‐Keefe Carol J.
Published: November 2006

Insulin resistance and altered maternal metabolism in gestational diabetes mellitus (GDM) may impair fetal arachidonic acid (AA) and docosahexaenoic acid (DHA) status. The objectives were to test the hypothesis that fetal polyunsaturated fatty acids would be altered with GDM and identify factors related to fetal phospholipid (PL) AA and DHA. Maternal and cord vein erythrocyte PL fatty acids were determined in GDM (n=13) and healthy pregnant women (controls, n=12). Cord vein erythrocyte PL AA and DHA concentrations were significantly lower in GDM vs. controls. Maternal blood hemoglobin A1C was inversely correlated to fetal erythrocyte PL DHA and AA in controls and GDM (n=25). Pregravid body mass index was negatively associated with fetal PL DHA. The data support the hypothesis that there is impairment in fetal accretion of DHA and AA in GDM.
Synthesis of 9,12‐Dioxo‐10(Z)‐dodecenoic acid, a new fatty acid metabolite derived from 9‐hydroperoxy‐10,12‐octadecadienoic acid in lentil seed (Lens culinaris medik.)
Authors: Gallasch Bernd A. W. , Spiteller Gerhard
Published: November 2006

The previously unknown linoleic acid peroxidation product 9,12‐dioxo‐10(Z)‐decenoic acid (Z5) was detected in lentil seed fluor (Lens culinaris Medik.) by electron impact mass spectrometry (El‐MS) after derivatization with pentafluorobenzyl‐hydroxylamine‐hydrochloride, methylation of acidic groups with diazomethane, and protection of hydroxylic groups with N‐methyl‐N‐trimethylsilyl‐trifluoroacetamide. The structure of the natural product was confirmed by synthesis of Z5, 9,12‐dioxo‐10(E)‐decenoic acid, and derivatives. EI‐MS, nuclear magnetic resonance and gas chromatographic data of these compounds and synthetic intermediates are discussed.
Comparison of growth and fatty acid metabolism in rats fed diets containing equal levels of γ‐linolenic acid from high γ‐linolenic acid canola oil or borage oil
Authors: Palombo John D. , DeMichele Stephen J. , Liu Jim‐Wen , Bistrian Bruce R. , Huang Yung‐Sheng
Published: November 2006

We have utilized transgenic technology to develop a new source of γ‐linolenic acid (GLA) using the canola plant as a host. The aim of the present study was to compare the growth and fatty acid metabolism in rats fed equal amounts of GLA obtained from the transgenic canola plant relative to GLA from the borage plant. Young male Sprague‐Dawley rats (n=10/group) were randomized and fed a purified AIN93G diet (10% lipid by weight) containing either a mixture of high GLA canola oil (HGCO) and corn oil or a control diet containing borage oil (BO) for 6 wk. GLA accounted for 23% of the triglyceride fatty acids in both diets. Growth and diet consumption were monitored every 2–3 d throughout the study. At study termination, the fatty acid composition of the liver and plasma phospholipids was analyzed by gas chromatography. The growth and diet consumption of the HGCO group were similar to the BO group. There were no adverse effects of either diet on the general health or appearance of the rats, or on the morphology of the major organs. There was no significant difference between the diet groups for total percentage of n−6 polyunsaturated fatty acids present in either the total or individual phospholipid fractions of liver or plasma. The relative percentage of GLA and its main metabolite, arachidonic acid, in each phospholipid fraction of liver or plasma were also similar between groups. The percentage of 18∶2n−6 in liver phosphatidylethanolamine and phosphatidylinositol/serine was higher (P<0.05) and 22∶5n−6 was lower in the HGCO group than the BO group. This finding could be attributed to the higher 18∶3n−3 content in the HGCO diet than the BO diet. Results from this long‐term feeding study of rats show for the first time that a diet containing transgenically modified canola oil was well‐tolerated, and had similar biological effects, i.e., growth characteristics and hepatic metabolism of n−6 fatty acids, as a diet containing borage oil.