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At least 775 records · Page 43Linked to original sources
PubMed1999

Sex-related differences in response of plasma lipids to simvastatin: the Saitama Postmenopausal Lipid Intervention Study. S-POLIS Group.

The Saitama Postmenopausal Lipid Intervention Study was a multicenter, uncontrolled, collaborative study that investigated tolerability and sex-related differences in the response of serum lipids to simvastatin administered for 12 months in 122 postmenopausal women and 55 men with serum total cholesterol (TC) levels > or =220 mg/dL. With simvastatin treatment, TC and low-density lipoprotein cholesterol (LDL-C) levels decreased significantly at 1 month in both groups, and these decreased levels were maintained throughout treatment (P < 0.001). A significant decrease in triglyceride (TG) levels was also observed in both groups (P < 0.05). The mean percentage decreases in TC and LDL-C levels in women (20% and 28%, respectively) were significantly greater than those in men (15% and 20%, respectively) (P < 0.001). Mean percentage changes in TC and LDL-C levels in subgroups defined by stratification for baseline TC and LDL-C levels were also greater in women. There were no sex-related differences in the percentage changes in TG or high-density cholesterol levels, although the changes were influenced by baseline levels. Although the median dose of simvastatin (milligrams per kilogram of body weight) in women was significantly higher than in men (P < 0.001), the percentage changes in serum lipids were not correlated with the doses of simvastatin calibrated by body weight. Adverse reactions occurred in 8 men and 7 women, so there appeared to be no significant sex-related difference. Eleven patients had abnormal laboratory values. Simvastatin therapy for 12 months is well tolerated and effective for both women and men with hypercholesterolemia. Sex-related differences occurred in the response to simvastatin therapy of serum lipids, especially TC and LDL-C, with greater changes in lipid levels occurring in women.

Aged↗
PubMed2002

Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in cosmetic and dermatological preparations.

Solid lipid nanoparticles (SLN) were developed at the beginning of the 1990 s as an alternative carrier system to emulsions, liposomes and polymeric nanoparticles. The paper reviews advantages-also potential limitations-of SLN for the use in topical cosmetic and pharmaceutical formulations. Features discussed include stabilisation of incorporated compounds, controlled release, occlusivity, film formation on skin including in vivo effects on the skin. As a novel type of lipid nanoparticles with solid matrix, the nanostructured lipid carriers (NLC) are presented, the structural specialties described and improvements discussed, for example, increase in loading capacity, physical and chemical long-term stability, triggered release and potentially supersaturated topical formulations. For both SLN and NLC, the technologies to produce the final topical formulation are described, especially the production of highly concentrated lipid nanoparticle dispersions >30-80% lipid content. Production issues also include clinical batch production, large scale production and regulatory aspects (e. g. status of excipients or proof of physical stability).

Administration, Topical↗
PubMed2002

Extraction of lipids from Mortierella alpina and enrichment of arachidonic acid from the fungal lipids.

Mortierella alpina is known as an arachidonic acid (AA) producing oleaginous fungus. Extraction of lipids from wet and dry M. alpina biomass was compared. Lipids yield of extraction from dry cells was higher than that of extraction from wet. Wet extraction mainly extracted lipid bodies and lipids in membranes did not extract effectively. Enrichment of AA from the fungal lipids by a urea inclusion method was studied. Most of the saturated and monounsaturated fatty acids, 93.0% and 84.6%, respectively, were removed by forming urea inclusion compounds. AA was concentrated after urea inclusion. Its content in total fatty acids increased 6.2-folds and reached 57.1% with a recovery of 81.9%.

Arachidonic Acid↗
PubMed2001

Fluorescence anisotropy measurements of lipid order in plasma membranes and lipid rafts from RBL-2H3 mast cells.

Specialized plasma membrane domains known as lipid rafts participate in signal transduction and other cellular processes, and their liquid ordered (L(o)) phase appears to be important for their function. To quantify ordered lipids in biological membranes, we investigated steady-state fluorescence anisotropy of two lipid probes, 2-[3-(diphenylhexatrienyl)propanoyl]-1-hexadecanoyl-sn-glycero-3-phosphocholine (DPH-PC) and N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine (NBD-PE). We show using model membranes with varying amounts of cholesterol that steady-state fluorescence anisotropy is a sensitive measure of cholesterol-dependent ordering. The results suggest that DPH-PC is a more sensitive probe than NBD-PE. In the presence of cholesterol, ordering also depends on the degree of saturation of the phospholipid acyl chains. Using DPH-PC, we find that the plasma membrane of RBL-2H3 mast cells is substantially ordered, roughly 40%, as determined by comparison with anisotropy values for model membranes entirely in a liquid ordered (L(o)) phase and in a liquid disordered (L(alpha)) phase. This result is consistent with the finding that approximately 30% of plasma membrane phospholipids are insoluble in 0.5% Triton X-100. Furthermore, detergent-resistant membranes isolated by sucrose gradient fractionation of Triton X-100 cell lysates are more ordered than plasma membrane vesicles, suggesting that they represent a more ordered subset of the plasma membrane. Treatment of plasma membrane vesicles with methyl-beta-cyclodextrin resulting in 75% cholesterol depletion leads to commensurate decreases in lipid order as measured by anisotropy of DPH-PC and NBD-PE. These results demonstrate that steady-state fluorescence anisotropy of DPH-PC is a useful way to measure the amount of lipid order in biological membranes.

Animals↗
PubMed2005

Lipid rafts prepared by different methods contain different connexin channels, but gap junctions are not lipid rafts.

Cell extraction with cold nonionic detergents or alkaline carbonate prepares an insoluble membrane fraction whose buoyant density permits its flotation in discontinuous sucrose gradients. These lipid "rafts" are implicated in protein sorting and are attractive candidates as platforms that coordinate signal transduction pathways with intracellular substrates. Gap junctions form a direct molecular signaling pathway by end-to-end apposition of hemichannels containing one (homomeric) or more (heteromeric) connexin isoforms. Residency of channels composed of Cx26 and/or Cx32 in lipid rafts was assessed by membrane insolubility in alkaline carbonate or different concentrations of Triton X100, Nonidet P40 and Brij-58 nonionic detergents. Using Triton X100, insoluble raft membranes contained homomeric Cx32 channels, but Cx26-containing channels only when low detergent concentrations were used. Results were similar using Nonidet P40, except that Cx26-containing channels were excluded from raft membranes at all detergent concentrations. In contrast, homomeric Cx26 channels were enriched within Brij-58-insoluble rafts, whereas Cx32-containing channels partitioned between raft and nonraft membranes. Immunofluorescence microscopy showed prominent colocalization only of nonjunctional connexin channels with raft plasma membrane; junctional plaques were not lipid rafts. Rafts prepared by different extraction methods had considerable quantitative and qualitative differences in their lipid compositions. That functionally different nonjunctional connexin channels partition among rafts with distinct lipid compositions suggests that unpaired Cx26 and/or Cx32 channels exist in membrane domains of slightly different physicochemical character. Rafts may be involved in trafficking of plasma membrane connexin channels to gap junctions.

Cell Extracts↗
PubMed2002

Role of beer lipid-binding proteins in preventing lipid destabilization of foam.

The negative effect of fatty acids on the foam stability of beer has been assessed. Long-chain fatty acids are far more damaging than short-chain fatty acids on the foam stability of beer at the concentrations employed. Polypeptides have been isolated from an all malt beer by hydrophobic interaction chromatography. Using this technique five groups of polypeptides were isolated, group 1 being the least hydrophobic and group 5 the most hydrophobic, all of which exhibited similar polypeptide compositions by SDS-PAGE. All five hydrophobic polypeptide groups bound [(14)C]linoleic acid; however, group 5, the most hydrophobic group, bound the most linoleic acid. Groups 1 and 5 were titrated with cis-parinaric acid (CPA) to produce binding curves, which were compared with a binding curve obtained for bovine serum albumin (BSA). Groups 1 and 5 both produced binding curves that saturated at approximately 5.5 microM and 4 microM CPA and had association constants (K(a)) of 6.27 x 10(7) and 1.62 x 10(7) M(-1), respectively. In comparison, BSA produced a binding curve that saturated at 6 microM CPA and had a K(a) of 3.95 x 10(7) M(-1). Further investigation has shown that group 1 is pH sensitive and group 5 pH insensitive with respect to lipid binding. The lipid-binding activity of group 5 was also shown to be unaffected by ethanol concentration. Linoleic acid (5 microM) when added to beer resulted in unstable foam. Group 5 was added to the lipid-damaged beer and was shown to restore the foam stability to values that were obtained for the control beer. It has therefore been demonstrated that proteins isolated from beer have a lipid-binding capacity and that they can convey a degree of protection against lipid-induced foam destabilization.

Beer↗
PubMed2005

Electron spin resonance spin trapping for analysis of lipid oxidation in oils: inhibiting effect of the spin trap alpha-phenyl-N-tert-butylnitrone on lipid oxidation.

The electron spin resonance (ESR) spin trapping technique was investigated as an analytical approach to follow lipid oxidation of rapeseed oil, sunflower oil, and fish oil during storage at 40 degrees C. Unlike previous investigations, alpha-phenyl-N-tert-butylnitrone (PBN), used as spin trap, was added to the fresh oils and formation of radicals was monitored during storage. Results were compared with the development in peroxide value (PV) and the thiobarbituric acid index (TBA). Increasing radical development was detected during the initial stages of oxidation, during which no significant changes in PV and TBA were observed. Evidence of spin adduct depletion was found during prolonged storage, suggesting that although spin trapping of radicals may be used to follow early events in lipid oxidation, it is not a suitable parameter for long periods of time. Addition of the spin trap after sequential samplings is recommended for getting an insight of oxidative changes during storage. Further, the influence of the spin trap (PBN) on lipid oxidation was studied in detail by application of PV and TBA and by following the depletion of naturally occurring tocopherol. PBN was found to possess a profound inhibiting effect on lipid oxidation. Such an effect was found to be dependent on the nature of the oil, and it was observed that the lower the oxidative stability, the larger the effect of PBN on lipid oxidation. This effect was interpreted in terms of the capability of PBN to react with peroxyl radicals, which in turn depends on the initial tocopherol content of the oils.

Cyclic N-Oxides↗
PubMed2000

Evaluation of lipid ultraviolet absorption as a parameter to measure lipid oxidation in dark chicken meat.

The application of lipid UV absorption (235, 269, and 280 nm) to follow up lipid oxidation in dark chicken meat has been evaluated using raw and cooked samples with different alpha-tocopherol contents (modulated by dietary supplementation). To this purpose, when absorption was measured at 235 nm, second-derivative spectrophotometry did not show any significant advantage over nonderivative spectrophotometry. For absorption at 269 and 280 nm, nonderivative spectrophotometry more sensitively monitored lipid oxidation than second- and third-derivative spectrophotometry. In addition, only direct measurements at 235 and 269 nm and second-derivative measurements at 235 nm showed a limited usefulness to follow up lipid oxidation in our samples. However, these UV absorption parameters were much less effective than lipid hydroperoxide values measured through a ferrous oxidation-xylenol orange method and 2-thiobarbituric acid values determined by a third-derivative spectrophotometric method with acid aqueous extraction.

Animals↗
PubMed1997

Effect of tamoxifen on lipids and lipid metabolising marker enzymes in experimental atherosclerosis in Wistar rats.

Tamoxifen, a non-steroidal anti-oestrogen, is used in the treatment of breast cancer, both receptor positive and negative tumours. It also possesses weak oestrogenic activity which forms the basis of this study. Tamoxifen (2 different dosages) was administered through diet (10 mg/kg diet and 20 mg/kg diet) to experimental atherosclerosis induced female rats to assess the effect of tamoxifen on plasma lipid levels, lipoprotein cholesterol level and on the activity of lipid metabolising enzymes. The plasma total lipid level was increased in atherosclerosis suffering animals compared to control animals with concomitant changes in the activity of lipid metabolising enzymes. HDL-cholesterol was decreased while LDL-cholesterol and VLDL-cholesterol were increased in the atherosclerosis induced group. Cholesterol and free cholesterol were decreased in tamoxifen treated groups while the other lipids show a moderate increase. HDL-cholesterol was increased but LDL-cholesterol was decreased in the tamoxifen treated groups. The higher dosage tamoxifen given group animals show significantly favourable results from therapy stand point when compared to diseased group.

Animals↗
PubMed2005

Lipid peroxides in obese patients and effects of weight loss with orlistat on lipid peroxides levels.

OBJECTIVE: Obesity is a well-known risk factor of atherosclerosis. Recent studies showed that obesity is associated with enhanced lipid peroxidation. The aim of this study is to investigate the effect of weight reduction with orlistat treatment on lipid peroxidation levels. We assessed lipid peroxidation by measuring the concentration of plasma malondialdehyde (MDA). DESIGN: A randomized, controlled, open-label 6-month study. SUBJECTS: In total, 36 obese (body mass index (BMI) >30 kg/m2) and 11 healthy age-matched control subjects were enrolled in the study. MEASUREMENTS: Fasting glucose, triglyceride, total cholesterol, HDL cholesterol and LDL cholesterol and MDA levels were measured in both groups. Obese subjects received orlistat, 120 mg three times daily together with hypocaloric diet. After 6 months of treatment laboratory tests were repeated. RESULTS: MDA levels were significantly higher in obese patients than the control group (P<0.0001). After 6 months of treatment in obese subjects, the mean weight of the patients decreased by 6.8 kg, the BMI by 3.2 kg/m2. Plasma MDA levels were significantly reduced by weight loss from 2+/-0.77 to 0.89+/-0.41 nmol/ml (P<0.001). BMI correlated with MDA levels at baseline (r=0.6, P<0.0001). Changes in BMI was positively associated with plasma MDA level reduction (r=0.36, P<0.05). CONCLUSION: These results indicate that obesity is associated with increases in endogenous lipid peroxides. Our data show that the indicator of lipid peroxidation-MDA-falls markedly in association with weight loss with orlistat. The demonstration of decreased free radical generation has important implications for oxidative mechanism underlying obesity-associated disorders.

Adult↗
PubMed2006

Basis for improved permeability barrier homeostasis induced by PPAR and LXR activators: liposensors stimulate lipid synthesis, lamellar body secretion, and post-secretory lipid processing.

Previously, we demonstrated that topical applications of peroxisome proliferator-activated receptors (PPARs) and liver X receptor (LXR) activators improve permeability barrier homeostasis. We showed further that stimulation of epidermal differentiation provides one mechanism that could account for such improvement. Here, we studied the effects of these agents on the lipid matrix of the stratum corneum. Hairless mice were treated topically with activators of PPARalpha (WY14643), PPARdelta (GW1514), PPARgamma (ciglitazone), and LXR (22(R)-cholesterol or TO901317) or vehicle twice daily for 3 days. All activators significantly increased epidermal cholesterol, fatty acid, and sphingolipid synthesis, including the production of barrier-specific ceramide species. In addition, lamellar body (LB) formation, secretion, and post-secretory processing accelerated significantly following acute barrier disruption in PPAR/LXR-activator-treated animals. Finally, the activity of epidermal beta-glucocerebrosidase, a key lipid-processing enzyme, increased in PPAR/LXR-activator-treated animals. Thus, topical PPAR and LXR activators stimulate epidermal lipid synthesis, increase LB secretion, and accelerate extracellular lipid processing, providing additional mechanisms that further account for their ability to improve epidermal permeability barrier homeostasis. Since the liposensors are activated by endogenous lipid metabolites, they may serve as unique regulators of barrier homeostasis.

Animals↗
PubMedDate not supplied

Relation between dietary lipid level and voluntary feed intake, growth, nutrient gain, lipid deposition and hepatic lipogenesis in rainbow trout.

Four diets with differing lipid contents (15, 20, 25 or 30% DM) were tested on small (initial body weight: 27 g) and larger (IBW: 93 g) rainbow trout (Oncorhynchus mykiss) fed on demand or by hand, respectively. In both trials, voluntary feed intake was inversely related to dietary lipid levels. Protein efficiency increased when dietary fat content increased. Final whole-body lipid content was positively related to dietary lipid levels. The main sites of lipid storage were visceral adipose tissue and to a lesser extent muscle. Increased fat deposition in the visceral cavity of young trout was due to both hyperplasic and hypertrophic responses and in larger trout mostly due to a hypertrophic response. Liver activities of glucose-6-phosphate dehydrogenase and fatty acid synthetase were negatively correlated with fat intake and positively with starch intake, whereas malic enzyme was little affected by dietary treatments.

Adipose Tissue↗
PubMed2006

Correction of apparent finite size effects in the area per lipid of lipid membranes simulations.

Molecular dynamics simulations of lipids bilayers have reported that the average area per lipid increases with the size of the simulated unit cell under constant temperature, pressure, and number of molecules. Here we show that the cause of this finite size effect are artifacts associated with the heat bath coupling. This can be corrected by coupling individually each degree of freedom to the heat bath, instead of coupling globally the system. We present the results of the investigation on three aspects of molecular dynamics simulations and their effect on the computed average area per lipid: (I) the accuracy in the computation of electrostatic interactions, the energy, and the virial, (II) long range Lennard-Jones interactions for systems with symmetry in one plane, and (III) thermodynamic baths. We show that the average area per lipid remains constant for simulations of systems containing 32, 64, and 256 lipids.

Artifacts↗
PubMed1981

Specific antibody-dependent interactions between macrophages and lipid haptens in planar lipid monolayers.

The binding of guinea pig peritoneal macrophages to planar lipid monolayers on alkylated glass is shown to be highly specific, requiring lipid hapten in the monolayer and specific anti-hapten IgG antibody. This is true for both "fluid" and "solid" monolayer membranes, in which the lateral diffusion coefficients of fluorescent lipid probes and bound fluorescent antibodies differ by at least two orders of magnitude. The region of the (macrophage membrane)--(monolayer membrane) contact is readily observed by using an epifluorescence microscope and fluoresceinated IgG antibodies or fluorescent lipids. The fluorescence intensity of IgG antibodies bound to lipid haptens in fluid monolayer membranes in the region of the (macrophage membrane)--(monolayer membrane) contact was significantly enhanced in the early stages of binding (first 10 min at 24 degrees C), due to a diffusive flux of the fluorescent antibodies into the region of membrane--membrane contact. Cellular activation takes place immediately during a 10-min warm-up to 37 degrees C and can be recognized by rapid symmetrical cell spreading, the formation of "black holes" around the cells (probably due to superoxide-facilitated photochemical bleaching of the fluorophore), and the release of the lysozomal enzyme cathepsin B. Specific antibody-dependent [1-14C]-glucose oxidation by these macrophages on fluid and solid monolayers is quite similar to that reported previously for fluid and solid bilayer vesicle target membranes. These results are significant for understanding the molecular interactions between membranes that are necessary for a macrophage cytotoxic response.

Animals↗
PubMed1996

Physical states of surface and core lipids in lipid emulsions and apolipoprotein binding to the emulsion surface.

Plasma triglyceride-rich lipoproteins vary in lipid composition during their metabolism. We investigated the effects of the lipid composition of emulsion particles, specifically those of cholesterol enrichment and core replacement (replacing core triglyceride with cholesteryl oleate), on the physical states of surface and core lipids. Steady-state and time-resolved fluorescence anisotropies were measured in lipid emulsions using 1,6-diphenylhexatriene to probe the core and 1,6-diphenylhexatriene analogues for the outer and inner hydrophobic portions of surface phospholipids. In the absence of cholesterol, core replacement had little effect on the surface rigidity, despite the large difference in core mobility. However, core replacement caused a marked increase in surface rigidity in the presence of cholesterol. Quenching experiments using the fluorescent cholesterol analogue, dehydroergosterol, indicated that core replacement allowed surface dehydroergosterol to redistribute from the inner to the outer regions in the emulsion surface. These results indicated that core replacement modulates the surface properties of the emulsion particles through the redistribution of cholesterol in the surface layers. Furthermore, core replacement significantly decreased the binding of apolipoprotein E to the emulsion surface, whereas the binding of apolipoprotein CII responded to the cholesterol enrichment. This binding behavior of exchangeable apolipoproteins may closely correlate with the location of surface cholesterol and the mobility of core lipids.

Apolipoproteins↗
PubMed1998

A minimally lipidated form of cell-derived apolipoprotein E exhibits isoform-specific stimulation of neurite outgrowth in the absence of exogenous lipids or lipoproteins.

Within the central nervous system, apolipoprotein E (apoE) synthesis is increased in response to nerve injury, a finding that may reflect a role for apoE in neuronal remodeling. Recent studies show that apoE3 promotes and apoE4 inhibits neurite outgrowth in cultured neuronal cells. Interestingly, these isoform-specific effects are observed only when apoE is presented to cells in the presence of an exogenous lipid source such as rabbit beta-very low density lipoprotein (beta-VLDL), making it difficult to discern the biologically active form of apoE or to understand the role of the lipid source. In the present study we tested whether a cell-derived lipidated form of apoE can alter neurite outgrowth in the absence of beta-VLDL by constructing Neuro-2a cell lines expressing high levels of apoE. Our results showed that endogenous apoE3 stimulated neurite outgrowth, whereas the endogenous apoE4 isoform was neutral. Furthermore, beta-VLDL antagonized the stimulatory effects of the endogenous apoE3. Characterization of the secreted apoE3 indicated that the neurite outgrowth-stimulating activity could be recovered from culture medium with an anti-apoE immunoaffinity column and was present in a poorly lipidated particle with a density between 1.19 and 1.26 g/ml. These results indicated that the biological activity of apoE3 in stimulating neurite outgrowth was inherent in the cell-derived apoE particle and was not dependent on either (a) an interaction of apoE3 with an artificial lipid source or (b) independent actions of apoE3 and beta-VLDL.

Animals↗
PubMed2001

Barley lipid transfer protein, LTP1, contains a new type of lipid-like post-translational modification.

In plants a group of proteins termed nonspecific lipid transfer proteins are found. These proteins bind and catalyze transfer of lipids in vitro, but their in vivo function is unknown. They have been suggested to be involved in different aspects of plant physiology and cell biology, including the formation of cutin and involvement in stress and pathogen responses, but there is yet no direct demonstration of an in vivo function. We have found and characterized a novel post-translational modification of the barley nonspecific lipid transfer protein, LTP1. The protein-modification bond is of a new type in which an aspartic acid in LTP1 is bound to the modification through what most likely is an ester bond. The chemical structure of the modification has been characterized by means of two-dimensional homo- and heteronuclear nuclear magnetic resonance spectroscopy as well as mass spectrometry and is found to be lipid-like in nature. The modification does not resemble any standard lipid post-translational modification but is similar to a compound with known antimicrobial activity.

Amino Acids↗
PubMed2001

Lipid-protein interactions at the nicotinic acetylcholine receptor. A functional coupling between nicotinic receptors and phosphatidic acid-containing lipid bilayers.

The structural and functional properties of reconstituted nicotinic acetylcholine receptor membranes composed of phosphatidyl choline either with or without cholesterol and/or phosphatidic acid have been examined to test the hypothesis that receptor conformational equilibria are modulated by the physical properties of the surrounding lipid environment. Spectroscopic and chemical labeling data indicate that the receptor in phosphatidylcholine alone is stabilized in a desensitized-like state, whereas the presence of either cholesterol or phosphatidic acid favors a resting-like conformation. Membranes that effectively stabilize a resting-like state exhibit a relatively large proportion of non-hydrogen-bonded lipid ester carbonyls, suggesting a relatively tight packing of the lipid head groups and thus a well ordered membrane. Functional reconstituted membranes also exhibit gel-to-liquid crystal phase transition temperatures that are higher than those of nonfunctional reconstituted membranes composed of phosphatidylcholine alone. Significantly, incorporation of the receptor into phosphatidic acid-containing membranes leads to a dramatic increase in both the lateral packing densities and the gel-to-liquid crystal phase transition temperatures of the reconstituted lipid bilayers. These results suggest a functional link between the nicotinic acetylcholine receptor and the physical properties of phosphatidic acid-containing membranes that could underlie the mechanism by which this lipid preferentially enhances receptor function.

Animals↗