Differentiation of human keratinocytes: changes in lipid synthesis, plasma membrane lipid composition, and 125I-EGF binding upon administration of 25-hydroxycholesterol and mevinolin

International Nuclear Information System (INIS)

Ponec, M.; Kempenaar, J.; Weerheim, A.; Boonstra, J.

1987-01-01

We have studied the relationship between differentiation capacity, plasma membrane composition, and epidermal growth factor (EGF) receptor expression of normal keratinocytes in vitro. The plasma membrane composition of the cells was modulated experimentally by cholesterol depletion, using specific inhibitors of cholesterol synthesis, such as 25-hydroxycholesterol and mevinolin. Exposure of the cells towards these inhibitors resulted in a drastic decrease of cholesterol biosynthesis, as determined from 14 C-acetate incorporation into the various lipid fractions. This effect on cholesterol biosynthesis was reflected by changes in plasma membrane composition, as determined by lipid analysis of isolated plasma membrane fractions, these resulting in a decreased cholesterol-phospholipid ratio. The experimental modulation of plasma membrane composition by 25-hydroxycholesterol or mevinolin were accompanied by a decreased cornified envelope formation and by high expression of EGF binding sites. These phenomena were more pronounced in cells induced to differentiate by exposure of cells grown under low Ca2+ to normal Ca2+ concentrations, as compared to cells grown persistently under low Ca2+ concentrations. These results suggest a close correlation between plasma membrane composition, differentiation capacity, and EGF receptor expression

Effect of dietary cholesterol and plant sterol consumption on plasma lipid responsiveness and cholesterol trafficking in healthy individuals.

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Alphonse, Peter A S; Ramprasath, Vanu; Jones, Peter J H

2017-01-01

Dietary cholesterol and plant sterols differentially modulate cholesterol kinetics and circulating cholesterol. Understanding how healthy individuals with their inherent variabilities in cholesterol trafficking respond to such dietary sterols will aid in improving strategies for effective cholesterol lowering and alleviation of CVD risk. The objectives of this study were to assess plasma lipid responsiveness to dietary cholesterol v. plant sterol consumption, and to determine the response in rates of cholesterol absorption and synthesis to each sterol using stable isotope approaches in healthy individuals. A randomised, double-blinded, crossover, placebo-controlled clinical trial (n 49) with three treatment phases of 4-week duration were conducted in a Manitoba Hutterite population. During each phase, participants consumed one of the three treatments as a milkshake containing 600 mg/d dietary cholesterol, 2 g/d plant sterols or a control after breakfast meal. Plasma lipid profile was determined and cholesterol absorption and synthesis were measured by oral administration of [3, 4-13C] cholesterol and 2H-labelled water, respectively. Dietary cholesterol consumption increased total (0·16 (sem 0·06) mmol/l, P=0·0179) and HDL-cholesterol (0·08 (sem 0·03) mmol/l, P=0·0216) concentrations with no changes in cholesterol absorption or synthesis. Plant sterol consumption failed to reduce LDL-cholesterol concentrations despite showing a reduction (6 %, P=0·0004) in cholesterol absorption. An over-compensatory reciprocal increase in cholesterol synthesis (36 %, P=0·0026) corresponding to a small reduction in absorption was observed with plant sterol consumption, possibly resulting in reduced LDL-cholesterol lowering efficacy of plant sterols. These data suggest that inter-individual variability in cholesterol trafficking mechanisms may profoundly impact plasma lipid responses to dietary sterols in healthy individuals.

Role of cholesterol on the transfection barriers of cationic lipid/DNA complexes

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Pozzi, Daniela; Cardarelli, Francesco; Salomone, Fabrizio; Marchini, Cristina; Amenitsch, Heinz; Barbera, Giorgia La; Caracciolo, Giulio

2014-08-01

Most lipid formulations need cholesterol for efficient transfection, but the precise motivation remains unclear. Here, we have investigated the effect of cholesterol on the transfection efficiency (TE) of cationic liposomes made of 1,2-dioleoyl-3-trimethylammonium-propane and dioleoylphosphocholine in Chinese hamster ovary cells. The transfection mechanisms of cholesterol-containing lipoplexes have been investigated by TE, synchrotron small angle X-ray scattering, and laser scanning confocal microscopy experiments. We prove that cholesterol-containing lipoplexes enter the cells using different endocytosis pathways. Formulations with high cholesterol content efficiently escape from endosomes and exhibit a lamellar-nonlamellar phase transition in mixture with biomembrane mimicking lipid formulations. This might explain both the DNA release ability and the high transfection efficiency. These studies highlight the enrichment in cholesterol as a decisive factor for transfection and will contribute to the rational design of lipid nanocarriers with superior TE.

How cholesterol interacts with proteins and lipids during its intracellular transport

DEFF Research Database (Denmark)

Wüstner, Daniel; Solanko, Katarzyna

2015-01-01

as well as by non-vesicular sterol exchange between organelles. In this article, we will review recent progress in elucidating sterol-lipid and sterol-protein interactions contributing to proper sterol transport in living cells. We outline recent biophysical models of cholesterol distribution and dynamics...... for characterization of sterol-protein interactions and for monitoring intracellular sterol transport. Finally, we review recent work on the molecular mechanisms underlying lipoprotein-mediated cholesterol import into mammalian cells and describe the process of cellular cholesterol efflux. Overall, we emphasize how......Sterols, as cholesterol in mammalian cells and ergosterol in fungi, are indispensable molecules for proper functioning and nanoscale organization of the plasma membrane. Synthesis, uptake and efflux of cholesterol are regulated by a variety of protein-lipid and protein-protein interactions...

The structural role of cholesterol in cell membranes: from condensed bilayers to lipid rafts.

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Krause, Martin R; Regen, Steven L

2014-12-16

CONSPECTUS: Defining the two-dimensional structure of cell membranes represents one of the most daunting challenges currently facing chemists, biochemists, and biophysicists. In particular, the time-averaged lateral organization of the lipids and proteins that make up these natural enclosures has yet to be established. As the classic Singer-Nicolson model of cell membranes has evolved over the past 40 years, special attention has focused on the structural role played by cholesterol, a key component that represents ca. 30% of the total lipids that are present. Despite extensive studies with model membranes, two fundamental issues have remained a mystery: (i) the mechanism by which cholesterol condenses low-melting lipids by uncoiling their acyl chains and (ii) the thermodynamics of the interaction between cholesterol and high- and low-melting lipids. The latter bears directly on one of the most popular notions in modern cell biology, that is, the lipid raft hypothesis, whereby cholesterol is thought to combine with high-melting lipids to form "lipid rafts" that float in a "sea" of low-melting lipids. In this Account, we first describe a chemical approach that we have developed in our laboratories that has allowed us to quantify the interactions between exchangeable mimics of cholesterol and low- and high-melting lipids in model membranes. In essence, this "nearest-neighbor recognition" (NNR) method involves the synthesis of dimeric forms of these lipids that contain a disulfide moiety as a linker. By means of thiolate-disulfide interchange reactions, equilibrium mixtures of dimers are then formed. These exchange reactions are initiated either by adding dithiothreitol to a liposomal dispersion to generate a small amount of thiol monomer or by including a small amount of thiol monomer in the liposomes at pH 5.0 and then raising the pH to 7.4. We then show how such NNR measurements have allowed us to distinguish between two very different mechanisms that have been

Calcium intake, body composition, and lipoprotein-lipid concentrations in adults.

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Jacqmain, Mélanie; Doucet, Eric; Després, Jean-Pierre; Bouchard, Claude; Tremblay, Angelo

2003-06-01

Recent data suggest that variations in calcium intake may influence lipid metabolism and body composition. The association between daily calcium intake and body composition and plasma lipoprotein-lipid concentrations was studied cross-sectionally in adults from phase 2 of the Québec Family Study. Adults aged 20-65 y (235 men, 235 women) were studied. Subjects who consumed vitamin or mineral supplements were excluded. Subjects were divided into 3 groups on the basis of their daily calcium intake: groups A ( 1000 mg). Daily calcium intake was negatively correlated with plasma LDL cholesterol, total cholesterol, and total:HDL cholesterol in women and men after adjustment for variations in body fat mass and waist circumference (P body fat mass and waist circumference. In women, body weight, percentage body fat, fat mass, body mass index, waist circumference, and total abdominal adipose tissue area measured by computed tomography were significantly greater (P < 0.05) in group A than in groups B and C, even after adjustments for confounding variables. Comparable trends were observed in men, but not after adjustment for the same covariates. A low daily calcium intake is associated with greater adiposity, particularly in women. In both sexes, a high calcium intake is associated with a plasma lipoprotein-lipid profile predictive of a lower risk of coronary heart disease risk compared with a low calcium intake.

Down-regulation of lipid raft-associated onco-proteins via cholesterol-dependent lipid raft internalization in docosahexaenoic acid-induced apoptosis.

Science.gov (United States)

Lee, Eun Jeong; Yun, Un-Jung; Koo, Kyung Hee; Sung, Jee Young; Shim, Jaegal; Ye, Sang-Kyu; Hong, Kyeong-Man; Kim, Yong-Nyun

2014-01-01

Lipid rafts, plasma membrane microdomains, are important for cell survival signaling and cholesterol is a critical lipid component for lipid raft integrity and function. DHA is known to have poor affinity for cholesterol and it influences lipid rafts. Here, we investigated a mechanism underlying the anti-cancer effects of DHA using a human breast cancer cell line, MDA-MB-231. We found that DHA decreased cell surface levels of lipid rafts via their internalization, which was partially reversed by cholesterol addition. With DHA treatment, caveolin-1, a marker for rafts, and EGFR were colocalized with LAMP-1, a lysosomal marker, in a cholesterol-dependent manner, indicating that DHA induces raft fusion with lysosomes. DHA not only displaced several raft-associated onco-proteins, including EGFR, Hsp90, Akt, and Src, from the rafts but also decreased total levels of those proteins via multiple pathways, including the proteasomal and lysosomal pathways, thereby decreasing their activities. Hsp90 overexpression maintained its client proteins, EGFR and Akt, and attenuated DHA-induced cell death. In addition, overexpression of Akt or constitutively active Akt attenuated DHA-induced apoptosis. All these data indicate that the anti-proliferative effect of DHA is mediated by targeting of lipid rafts via decreasing cell surface lipid rafts by their internalization, thereby decreasing raft-associated onco-proteins via proteasomal and lysosomal pathways and decreasing Hsp90 chaperone function. © 2013.

Organization of fluorescent cholesterol analogs in lipid bilayers - lessons from cyclodextrin extraction.

Science.gov (United States)

Milles, Sigrid; Meyer, Thomas; Scheidt, Holger A; Schwarzer, Roland; Thomas, Lars; Marek, Magdalena; Szente, Lajos; Bittman, Robert; Herrmann, Andreas; Günther Pomorski, Thomas; Huster, Daniel; Müller, Peter

2013-08-01

To characterize the structure and dynamics of cholesterol in membranes, fluorescent analogs of the native molecule have widely been employed. The cholesterol content in membranes is in general manipulated by using water-soluble cyclodextrins. Since the interactions between cyclodextrins and fluorescent-labeled cholesterol have not been investigated in detail so far, we have compared the cyclodextrin-mediated membrane extraction of three different fluorescent cholesterol analogs (one bearing a NBD and two bearing BODIPY moieties). Extraction of these analogs was followed by measuring the Förster resonance energy transfer between a rhodamine moiety linked to phosphatidylethanolamine and the labeled cholesterol. The extraction kinetics revealed that the analogs are differently extracted from membranes. We examined the orientation of the analogs within the membrane and their influence on lipid condensation using NMR and EPR spectroscopies. Our data indicate that the extraction of fluorescent sterols from membranes is determined by several parameters, including their impact on lipid order, their hydrophobicity, their intermolecular interactions with surrounding lipids, their orientation within the bilayer, and their affinity with the exogenous acceptor. Copyright © 2013 Elsevier B.V. All rights reserved.

Lipid chain saturation and the cholesterol in the phospholipid membrane affect the spectroscopic properties of lipophilic dye nile red

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Halder, Animesh; Saha, Baishakhi; Maity, Pabitra; Kumar, Gopinatha Suresh; Sinha, Deepak Kumar; Karmakar, Sanat

2018-02-01

We have studied the effect of composition and the phase state of phospholipid membranes on the emission spectrum, anisotropy and lifetime of a lipophilic fluorescence probe nile red. Fluorescence spectrum of nile red in membranes containing cholesterol has also been investigated in order to get insights into the influence of cholesterol on the phospholipid membranes. Maximum emission wavelength (λem) of nile red in the fluid phase of saturated and unsaturated phospholipids was found to differ by 10 nm. The λem was also found to be independent of chain length and charge of the membrane. However, the λem is strongly dependent on the temperature in the gel phase. The λem and rotational diffusion rate decrease, whereas the anisotropy and lifetime increase markedly with increasing cholesterol concentration for saturated phosoholipids, such as, dimyristoyl phosphatidylcholine (DMPC) in the liquid ordered phase. However, these spectroscopic properties do not alter significantly in case of unsaturated phospholipids, such as, dioleoyl phosphatidylcholine (DOPC) in liquid disordered phase. Interestingly, red edge excitation shift (REES) in the presence of lipid-cholesterol membranes is the direct consequences of change in rotational diffusion due to motional restriction of lipids in the presence of cholesterol. This study provides correlations between the membrane compositions and fluorescence spectral features which can be utilized in a wide range of biophysical fields as well the cell biology.

Cholesterol autoxidation in phospholipid membrane bilayers

International Nuclear Information System (INIS)

Sevanian, A.; McLeod, L.L.

1987-01-01

Lipid peroxidation in unilamellar liposomes of known cholesterol-phospholipid composition was monitored under conditions of autoxidation or as induced by a superoxide radical generating system, gamma-irradiation or cumene hydroperoxide. Formation of cholesterol oxidation products was indexed to the level of lipid peroxidation. The major cholesterol oxidation products identified were 7-keto-cholesterol, isomeric cholesterol 5,6-epoxides, isomeric 7-hydroperoxides and isomeric 3,7-cholestane diols. Other commonly encountered products included 3,5-cholestadiene-7-one and cholestane-3 beta, 5 alpha, 6 beta-triol. Superoxide-dependent peroxidation required iron and produced a gradual increase in 7-keto-cholesterol and cholesterol epoxides. Cholesterol oxidation was greatest in liposomes containing high proportions of unsaturated phospholipid to cholesterol (4:1 molar ratio), intermediate with low phospholipid to cholesterol ratios (2:1) and least in liposomes prepared with dipalmitoylphosphatidylcholine and cholesterol. This relationship held regardless of the oxidizing conditions used. Cumene hydroperoxide-dependent lipid peroxidation and/or more prolonged oxidations with other oxidizing systems yielded a variety of products where cholesterol-5 beta,6 beta-epoxide, 7-ketocholesterol and the 7-hydroperoxides were most consistently elevated. Oxyradical initiation of lipid peroxidation produced a pattern of cholesterol oxidation products distinguishable from the pattern derived by cumene hydroperoxide-dependent peroxidation

N-stearoylethanolamine restores pancreas lipid composition in obesity-induced insulin resistant rats.

Science.gov (United States)

Onopchenko, Oleksandra V; Kosiakova, Galina V; Oz, Murat; Klimashevsky, Vitaliy M; Gula, Nadiya M

2015-01-01

This study investigates the protective effect of N-stearoylethanolamine (NSE), a bioactive N-acylethanolamine , on the lipid profile distribution in the pancreas of obesity-induced insulin resistant (IR) rats fed with prolonged high fat diet (58% of fat for 6 months). The phospholipid composition was determined using 2D thin-layer chromatography. The level of individual phospholipids was estimated by measuring inorganic phosphorus content. The fatty acid (FA) composition and cholesterol level were investigated by gas-liquid chromatography. Compared to controls, plasma levels of triglycerides and insulin were significantly increased in IR rats. The pancreas lipid composition indicated a significant reduction of the free cholesterol level and some phospholipids such as phosphatidylcholine (PtdCho), phosphatidylethanolamine (PtdEtn), phosphatidylinositol (PtdIns), phosphatidylserine (PtdSer) compared to controls. Moreover, the FA composition of pancreas showed a significant redistribution of the main FA (18:1n-9, 18:2n-6, 18:3n-6 and 20:4n-6) levels between phospholipid, free FA, triglyceride fractions under IR conditions that was accompanied by a change in the estimated activities of Δ9-, Δ6-, Δ5-desaturase. Administration of N-stearoylethanolamine (NSE, 50 mg/kg daily per os for 2 weeks) IR rats triggered an increase in the content of free cholesterol, PtdCho and normalization of PtdEtn, PtdSer level. Furthermore, the NSE modulated the activity of desaturases, thus influenced FA composition and restored the FA ratios in the lipid fractions. These NSE-induced changes were associated with a normalization of plasma triglyceride content, considerable decrease of insulin and index HOMA-IR level in rats under IR conditions.

Cholesterol effect on water permeability through DPPC and PSM lipid bilayers: a molecular dynamics study.

Science.gov (United States)

Saito, Hiroaki; Shinoda, Wataru

2011-12-29

Water permeability of two different lipid bilayers of dipalmitoylphosphatidylcholine (DPPC) and palmitoylsphingomyelin (PSM) in the absence and presence of cholesterol (0-50 mol %) have been studied by molecular dynamics simulations to elucidate the molecular mechanism of the reduction in water leakage across the membranes by the addition of cholesterol. An enhanced free energy barrier was observed in these membranes with increased cholesterol concentration, and this was explained by the reduced cavity density around the cholesterol in the hydrophobic membrane core. There was an increase of trans conformers in the hydrophobic lipid chains adjacent to the cholesterol, which reduced the cavity density. The enhanced free energy barrier was found to be the main reason to reduce the water permeability with increased cholesterol concentration. At low cholesterol concentrations the PSM bilayer exhibited a higher free energy barrier than the DPPC bilayer for water permeation, while at greater than 30 mol % of cholesterol the difference became minor. This tendency for the PSM and DPPC bilayers to resemble each other at higher cholesterol concentrations was similar to commonly observed trends in several structural properties, such as order parameters, cross-sectional area per molecule, and cavity density profiles in the hydrophobic regions of bilayer membranes. These results demonstrate that DPPC and PSM bilayers with high cholesterol contents possess similar physical properties, which suggests that the solubility of cholesterol in these lipid bilayers has importance for an understanding of multicomponent lipid membranes with cholesterol. © 2011 American Chemical Society

Influence of the membrane environment on cholesterol transfer.

Science.gov (United States)

Breidigan, Jeffrey Michael; Krzyzanowski, Natalie; Liu, Yangmingyue; Porcar, Lionel; Perez-Salas, Ursula

2017-12-01

Cholesterol, an essential component in biological membranes, is highly unevenly distributed within the cell, with most localized in the plasma membrane while only a small fraction is found in the endoplasmic reticulum, where it is synthesized. Cellular membranes differ in lipid composition and protein content, and these differences can exist across their leaflets too. This thermodynamic landscape that cellular membranes impose on cholesterol is expected to modulate its transport. To uncover the role the membrane environment has on cholesterol inter- and intra-membrane movement, we used time-resolved small angle neutron scattering to study the passive movement of cholesterol between and within membranes with varying degrees of saturation content. We found that cholesterol moves systematically slower as the degree of saturation in the membranes increases, from a palmitoyl oleyl phosphotidylcholine membrane, which is unsaturated, to a dipalmitoylphosphatidylcholine (DPPC) membrane, which is fully saturated. Additionally, we found that the energetic barrier to move cholesterol in these phosphatidylcholine membranes is independent of their relative lipid composition and remains constant for both flip-flop and exchange at ∼100 kJ/mol. Further, by replacing DPPC with the saturated lipid palmitoylsphingomyelin, an abundant saturated lipid of the outer leaflet of the plasma membrane, we found the rates decreased by a factor of two. This finding is in stark contrast with recent molecular dynamic simulations that predict a dramatic slow-down of seven orders of magnitude for cholesterol flipping in membranes with a similar phosphocholine and SM lipid composition. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

[The composition of lipids and lipid peroxidation in the pancreas of quails exposed to nitrates and correction by the amaranth's seeds].

Science.gov (United States)

Tsekhmistrenko, S I; Ponomarenko, N V

2013-01-01

Researches of features of lipid composition, functioning of the system of antioxidant defense, maintenance of lipid peroxidation products in the quail's pancreas on the early postnatal ontogenesis stages are conducted for actions of nitrates and feeding with amaranth's seeds in mixed fodder. The arrival of nitrates in the organism of quails results in the decline of general lipids maintenance and nonetherified fat acids in the pancreas. Using of amaranth's seeds in mixed fodder on the background of the nitrate loading results in the increase of activity of the enzimes system of antioxidant defence, the growth of general lipid level in the quail's pancreas. Thus in correlation with separate classes of lipid maintenance of cholesterol goes down for certain, whereas the maintenance of triacylglycerols and ethers of cholesterol rises. The results obtained in the researches show the ability of amaranth's seeds to avert oxidative stress in quail's pancreas under nitrates influence.

Free cholesterol is a potent regulator of lipid transfer protein function

International Nuclear Information System (INIS)

Morton, R.E.

1988-01-01

This study investigates the effect of altered lipoprotein free cholesterol (FC) content on the transfer of cholesteryl ester (CE) and triglyceride (TG) from very low- (VLDL), low- (LDL), and high-(HDL) density lipoproteins by the plasma-derived lipid transfer protein (LTP). The FC content of VLDL and HDL was selectively altered by incubating these lipoproteins with FC/phospholipid dispersions of varying composition. FC-modified lipoproteins were then equilibrated with [3H] TG, [14C]CE-labeled lipoproteins of another class to facilitate the subsequent modification of the radiolabeled donor lipoproteins. LTP was added and the extent of radiolabeled TG and CE transfer determined after 1 h. With either LDL or VLDL as lipid donor, an increase in the FC content of these lipoproteins caused a concentration-dependent inhibition (up to 50%) of CE transfer from these particles, without any significant effect on TG transfer. In contrast, with HDL as donor, increasing the HDL FC content had little effect on CE transfer from HDL, but markedly stimulated (up to 2.5-fold) the transfer of TG. This differential effect of FC on the unidirectional transfer of radiolabeled lipids from VLDL and HDL led to marked effects on LTP-facilitated net mass transfer of lipids. During long-term incubation of a constant amount of LTP with FC-modified VLDL and HDL, the extent of net mass transfer was linearly related to lipoprotein FC content; a 4-fold increase in FC content resulted in a 3-fold stimulation of the CE mass transferred to VLDL, which was coupled to an equimolar, reciprocal transfer of TG mass to HDL. Since lipid transfer between lipoproteins is integral to the process of reverse cholesterol transport, we conclude that lipoprotein FC levels are a potent, positive regulator of the pathways involved in sterol clearance. FC may modulate lipid transfer by altering the availability of CE and TG to LTP at the lipoprotein surface

Lipid Oxidation in Carriers of Lecithin: Cholesterol Acyltransferase Gene Mutations

NARCIS (Netherlands)

Holleboom, Adriaan G.; Daniil, Georgios; Fu, Xiaoming; Zhang, Renliang; Hovingh, G. Kees; Schimmel, Alinda W.; Kastelein, John J. P.; Stroes, Erik S. G.; Witztum, Joseph L.; Hutten, Barbara A.; Tsimikas, Sotirios; Hazen, Stanley L.; Chroni, Angeliki; Kuivenhoven, Jan Albert

2012-01-01

Objective-Lecithin:cholesterol acyltransferase (LCAT) has been shown to play a role in the depletion of lipid oxidation products, but this has so far not been studied in humans. In this study, we investigated processes and parameters relevant to lipid oxidation in carriers of functional LCAT

Lipid Oxidation in Carriers of Lecithin : Cholesterol Acyltransferase Gene Mutations

NARCIS (Netherlands)

Holleboom, Adriaan G.; Daniil, Georgios; Fu, Xiaoming; Zhang, Renliang; Hovingh, G. Kees; Schimmel, Alinda W.; Kastelein, John J. P.; Stroes, Erik S. G.; Witztum, Joseph L.; Hutten, Barbara A.; Tsimikas, Sotirios; Hazen, Stanley L.; Chroni, Angeliki; Kuivenhoven, Jan Albert

2012-01-01

OBJECTIVE: Lecithin:cholesterol acyltransferase (LCAT) has been shown to play a role in the depletion of lipid oxidation products, but this has so far not been studied in humans. In this study, we investigated processes and parameters relevant to lipid oxidation in carriers of functional LCAT

Structural properties of lipid reconstructs and lipid composition of normotensive and hypertensive rat vascular smooth muscle cell membranes

Directory of Open Access Journals (Sweden)

T.R. Oliveira

2009-09-01

Full Text Available Multiple cell membrane alterations have been reported to be the cause of various forms of hypertension. The present study focuses on the lipid portion of the membranes, characterizing the microviscosity of membranes reconstituted with lipids extracted from the aorta and mesenteric arteries of spontaneously hypertensive (SHR and normotensive control rat strains (WKY and NWR. Membrane-incorporated phospholipid spin labels were used to monitor the bilayer structure at different depths. The packing of lipids extracted from both aorta and mesenteric arteries of normotensive and hypertensive rats was similar. Lipid extract analysis showed similar phospholipid composition for all membranes. However, cholesterol content was lower in SHR arteries than in normotensive animal arteries. These findings contrast with the fact that the SHR aorta is hyporeactive while the SHR mesenteric artery is hyperreactive to vasopressor agents when compared to the vessels of normotensive animal strains. Hence, factors other than microviscosity of bulk lipids contribute to the vascular smooth muscle reactivity and hypertension of SHR. The excess cholesterol in the arteries of normotensive animal strains apparently is not dissolved in bulk lipids and is not directly related to vascular reactivity since it is present in both the aorta and mesenteric arteries. The lower cholesterol concentrations in SHR arteries may in fact result from metabolic differences due to the hypertensive state or to genes that co-segregate with those that determine hypertension during the process of strain selection.

Effect of lipid composition and packing on the adsorption of apolipoproteins to lipid monolayers

International Nuclear Information System (INIS)

Ibdah, J.A.; Lund-Katz, S.; Phillips, M.C.

1987-01-01

The monolayer system has been used to study the effects of lipoprotein surface lipid composition and packing on the affinities of apolipoproteins for the surfaces of lipoprotein particles. The adsorption of apolipoproteins injected beneath lipid monolayers prepared with pure lipids or lipoprotein surface lipids is evaluated by monitoring the surface pressure of the film and the surface concentration (Gamma) of 14 C-labelled apolipoprotein. At a given initial film pressure (π/sub i/) there is a higher adsorption of human apo A-I to unsaturated phosphatidylcholine (PC) monolayers compared to saturated PC monolayers (e.g., at π/sub i/ = 10 mN/m, Gamma = 0.35 and 0.06 mg/m 2 for egg PC and distearoyl PC, respectively, with 3 x 10 -4 mg/ml apo A-I in the subphase). In addition, adsorption of apo A-I is less to an egg sphingomyelin monolayer than to an egg PC monolayer. The adsorption of apo A-I to PC monolayers is decreased by addition of cholesterol. Generally, apo A-I adsorption diminishes as the lipid molecular area decreases. Apo A-I adsorbs more to monolayers prepared with HDL 3 surface lipids than with LDL surface lipids. These studies suggest that lipoprotein surface lipid composition and packing are crucial factors influencing the transfer and exchange of apolipoproteins among various lipoprotein classes during metabolism of lipoprotein particles

Cholesterol crystallization within hepatocyte lipid droplets and its role in murine NASH.

Science.gov (United States)

Ioannou, George N; Subramanian, Savitha; Chait, Alan; Haigh, W Geoffrey; Yeh, Matthew M; Farrell, Geoffrey C; Lee, Sum P; Savard, Christopher

2017-06-01

We recently reported that cholesterol crystals form in hepatocyte lipid droplets (LDs) in human and experimental nonalcoholic steatohepatitis. Herein, we assigned WT C57BL/6J mice to a high-fat (15%) diet for 6 months, supplemented with 0%, 0.25%, 0.5%, 0.75%, or 1% dietary cholesterol. Increasing dietary cholesterol led to cholesterol loading of the liver, but not of adipose tissue, resulting in fibrosing steatohepatitis at a dietary cholesterol concentration of ≥0.5%, whereas mice on lower-cholesterol diets developed only simple steatosis. Hepatic cholesterol crystals and crown-like structures also developed at a dietary cholesterol concentration ≥0.5%. Crown-like structures consisted of activated Kupffer cells (KCs) staining positive for NLRP3 and activated caspase 1, which surrounded and processed cholesterol crystal-containing remnant LDs of dead hepatocytes. The KCs processed LDs at the center of crown-like structures in the extracellular space by lysosomal enzymes, ultimately transforming into lipid-laden foam cells. When HepG2 cells were exposed to LDL cholesterol, they developed cholesterol crystals in LD membranes, which caused activation of THP1 cells (macrophages) grown in coculture; upregulation of TNF-alpha , NLRP3, and interleukin 1beta ( IL1β ) mRNA; and secretion of IL-1beta. In conclusion, cholesterol crystals form on the LD membrane of hepatocytes and cause activation and cholesterol loading of KCs that surround and process these LDs by lysosomal enzymes.

Trypanosoma cruzi Epimastigotes Are Able to Store and Mobilize High Amounts of Cholesterol in Reservosome Lipid Inclusions

Science.gov (United States)

Pereira, Miria G.; Nakayasu, Ernesto S.; Sant'Anna, Celso; De Cicco, Nuccia N. T.; Atella, Georgia C.; de Souza, Wanderley; Almeida, Igor C.; Cunha-e-Silva, Narcisa

2011-01-01

Background Reservosomes are lysosome-related organelles found in Trypanosoma cruzi epimastigotes. They represent the last step in epimastigote endocytic route, accumulating a set of proteins and enzymes related to protein digestion and lipid metabolism. The reservosome matrix contains planar membranes, vesicles and lipid inclusions. Some of the latter may assume rectangular or sword-shaped crystalloid forms surrounded by a phospholipid monolayer, resembling the cholesterol crystals in foam cells. Methodology/Principal Findings Using Nile Red fluorimetry and fluorescence microscopy, as well as electron microscopy, we have established a direct correlation between serum concentration in culture medium and the presence of crystalloid lipid inclusions. Starting from a reservosome purified fraction, we have developed a fractionation protocol to isolate lipid inclusions. Gas-chromatography mass-spectrometry (GC-MS) analysis revealed that lipid inclusions are composed mainly by cholesterol and cholesterol esters. Moreover, when the parasites with crystalloid lipid-loaded reservosomes were maintained in serum free medium for 48 hours the inclusions disappeared almost completely, including the sword shaped ones. Conclusions/Significance Taken together, our results suggest that epimastigote forms of T. cruzi store high amounts of neutral lipids from extracellular medium, mostly cholesterol or cholesterol esters inside reservosomes. Interestingly, the parasites are able to disassemble the reservosome cholesterol crystalloid inclusions when submitted to serum starvation. PMID:21818313

Cholesterol facilitates interactions between α-synuclein oligomers and charge-neutral membranes

DEFF Research Database (Denmark)

van Maarschalkerweerd, Andreas; Vetri, Valeria; Vestergaard, Bente

2015-01-01

composed of anionic lipids, while the more physiologically relevant zwitterionic lipids remain intact. We present experimental evidence for significant morphological changes in zwitterionic membranes containing cholesterol, induced by α-synuclein oligomers. Depending on the lipid composition, model...... of cholesterol for mediating interactions between physiologically relevant membranes and α-synuclein....

Lipid Extraction and Cholesterol Quantification: A Simple Protocol

Science.gov (United States)

Barreto, M. Carmo

2005-01-01

Enzymatic methods are used to measure cholesterol levels but a simple and inexpensive method is described, which is particularly important when one has repeated lab sessions during the week. It can be carried out on the organic phase containing the lipids, without evaporating the solvent, yielding quick results.

On the interaction between fluoxetine and lipid membranes: Effect of the lipid composition

Science.gov (United States)

Pham, Vy T.; Nguyen, Trinh Q.; Dao, Uyen P. N.; Nguyen, Trang T.

2018-02-01

Molecular interaction between the antidepressant fluoxetine and lipid bilayers was investigated in order to provide insights into the drug's incorporation to lipid membranes. In particular, the effects of lipid's unsaturation degree and cholesterol content on the partitioning of fluoxetine into large unilamellar vesicles (LUVs) comprised of unsaturated 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and saturated 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) were evaluated using second derivative spectrophotometry and Attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR). It was found that fluoxetine partitioned to a greater extent into the liquid-crystalline DOPC LUVs than into the solid-gel DPPC LUVs. The lipid physical state dependence of drug partitioning was verified by increasing the temperature in which the partition coefficient of fluoxetine significantly increased upon the change of the lipid phase from solid-gel to liquid-crystalline. The incorporation of 28 mol% cholesterol into the LUVs exerted a significant influence on the drug partitioning into both DOPC and DPPC LUVs. The ATR-FTIR study revealed that fluoxetine perturbed the conformation of DOPC more strongly than that of DPPC due to the cis-double bonds in the lipid acyl chains. Fluoxetine possibly bound to the carbonyl moiety of the lipids through the hydrogen bonding formation while displaced some water molecules surrounding the PO2- regions of the lipid head groups. Cholesterol, however, could lessen the interaction between fluoxetine and the carbonyl groups of both DOPC and DPPC LUVs. These findings provided a better understanding of the role of lipid structure and cholesterol on the interaction between fluoxetine and lipid membranes, shedding more light into the drug's therapeutic action.

Effect of cholesterol on structural and mechanical properties of membranes depends on lipid chain saturation

International Nuclear Information System (INIS)

Pan Jianjun; Tristram-Nagle, Stephanie; Nagle, John F.

2009-01-01

The effects of cholesterol on membrane bending modulus K C , membrane thickness D HH , the partial and apparent areas of cholesterol and lipid, and the order parameter S xray are shown to depend upon the number of saturated hydrocarbon chains in the lipid molecules. Particularly striking is the result that up to 40% cholesterol does not increase the bending modulus K C of membranes composed of phosphatidylcholine lipids with two cis monounsaturated chains, although it does have the expected stiffening effect on membranes composed of lipids with two saturated chains. The B fluctuational modulus in the smectic liquid crystal theory is obtained and used to discuss the interactions between bilayers. Our K C results motivate a theory of elastic moduli in the high cholesterol limit and they challenge the relevance of universality concepts. Although most of our results were obtained at 30 deg. C, additional data at other temperatures to allow consideration of a reduced temperature variable do not support universality for the effect of cholesterol on all lipid bilayers. If the concept of universality is to be valid, different numbers of saturated chains must be considered to create different universality classes. The above experimental results were obtained from analysis of x-ray scattering in the low angle and wide angle regions.

The effect of N-stearoylethanolamine on plasma lipid composition in rats with experimental insulin resistance

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O. V. Onopchenko

2015-02-01

Full Text Available A model of insulin resistance (IR, induced by prolonged high fat diet with high content of saturated fats was used to investigate the effect of N-stearoylethanolamine (NSE on the composition of free fatty acids (FFA, plasma lipoprotein spectrum and content of proinflammatory cytokine TNFα in rats. The results of this work showed a rise in the content of monounsaturated fatty acids (18:1 n-9 and a reduction in the level of polyunsaturated fatty acids (20:4 n-6 in plasma of rats with experimental IR. These findings are accompanied by the increased TNFα production and significant changes in plasma lipoprotein profile of rats with the fat overload. Particularly, a decreased high-density lipoprotein (HDL cholesterol level and increased low-density (LDL and very low-density lipoprotein (VLDL cholesterol level were detected. The NSE administration to obese rats with IR restored the content of mono- and polyunsaturated FFA, increased HDL cholesterol content and reduced LDL cholesterol level. In addition, the IR rats treated with NSE showed normalization in the serum TNFα level. Our results showed the restoration of plasma lipid profile under NSE administration in rats with obesity-induced IR. Considering the fact that plasma lipid composition displays the lipid metabolism in general, the NSE actions may play a significant role in the prevention of IR-associated complications.

NIR studies of cholesterol-dependent structural modification of the model lipid bilayer doped with inhalation anesthetics

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Kuć, Marta; Cieślik-Boczula, Katarzyna; Rospenk, Maria

2018-06-01

The influence of cholesterol on the structure of the model lipid bilayers treated with inhalation anesthetics (enflurane, isoflurane, sevoflurane and halothane) was investigated employing near-infrared (NIR) spectroscopy combined with the Principal Component Analysis (PCA). The conformational changes occurring in the hydrophobic area of the lipid bilayers were analyzed using the first overtones of symmetric (2νs) and antisymmetric (2νas) stretching vibrations of the CH2 groups of lipid aliphatic chains. The temperature values of chain-melting phase transition (Tm) of anesthetic-mixed dipalmitoylphosphatidylcholine (DPPC)/cholesterol and dipalmitoylphosphatidylglycerol (DPPG)/cholesterol membranes, which were obtained from the PCA analysis, were compared with cholesterol-free DPPC and DPPG bilayers mixed with inhalation anesthetics.

Acid sphingomyelinase activity is regulated by membrane lipids and facilitates cholesterol transfer by NPC2.

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Oninla, Vincent O; Breiden, Bernadette; Babalola, Jonathan O; Sandhoff, Konrad

2014-12-01

During endocytosis, membrane components move to intraluminal vesicles of the endolysosomal compartment for digestion. At the late endosomes, cholesterol is sorted out mainly by two sterol-binding proteins, Niemann-Pick protein type C (NPC)1 and NPC2. To study the NPC2-mediated intervesicular cholesterol transfer, we developed a liposomal assay system. (Abdul-Hammed, M., B. Breiden, M. A. Adebayo, J. O. Babalola, G. Schwarzmann, and K. Sandhoff. 2010. Role of endosomal membrane lipids and NPC2 in cholesterol transfer and membrane fusion. J. Lipid Res. 51: 1747-1760.) Anionic lipids stimulate cholesterol transfer between liposomes while SM inhibits it, even in the presence of anionic bis(monoacylglycero)phosphate (BMP). Preincubation of vesicles containing SM with acid sphingomyelinase (ASM) (SM phosphodiesterase, EC 3.1.4.12) results in hydrolysis of SM to ceramide (Cer), which enhances cholesterol transfer. Besides SM, ASM also cleaves liposomal phosphatidylcholine. Anionic phospholipids derived from the plasma membrane (phosphatidylglycerol and phosphatidic acid) stimulate SM and phosphatidylcholine hydrolysis by ASM more effectively than BMP, which is generated during endocytosis. ASM-mediated hydrolysis of liposomal SM was also stimulated by incorporation of diacylglycerol (DAG), Cer, and free fatty acids into the liposomal membranes. Conversely, phosphatidylcholine hydrolysis was inhibited by incorporation of cholesterol, Cer, DAG, monoacylglycerol, and fatty acids. Our data suggest that SM degradation by ASM is required for physiological secretion of cholesterol from the late endosomal compartment, and is a key regulator of endolysosomal lipid digestion. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.

Egg quality and yolk lipid composition of laying hens fed diets containing cashew nut meal

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Tatiana Fontoura Vidal

2013-03-01

Full Text Available The objective of this study was to assess the effect of the addition of cashew nuts meal (0, 5, 10, 15, 20, and 25% to laying hen diets on egg quality and yolk composition. The variables studied were: egg weight, specific gravity, Haugh Units, percentages of shell, albumen, and yolk, moisture, total solids, total lipids, fatty acids profile, and yolk cholesterol. The addition of up to 25% of cashew nuts meal to hen diets did not affect egg quality and freshness, moisture and total solids content. However, an increase in total lipid content and a decrease in yolk pigmentation was observed. Oleic acid level increased in the yolk, whereas palmitic, stearic, and linoleic acid levels decreased. The addition of cashew nuts meal increased the monounsaturated/saturated fatty acid ratio in the yolk and reduced the cholesterol content. Therefore, the use of cashew nuts meal in laying hen diets favorably modifies the fatty acid composition of egg yolk and contributes to a better acceptance of this food by consumers since it also reduces yolk cholesterol levels.

Clerodendron glandulosum Coleb., Verbenaceae, ameliorates high fat diet-induced alteration in lipid and cholesterol metabolism in rats

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RN Jadeja

Full Text Available The present study was undertaken to evaluate the efficacy of freeze dried extract of Clerodendron glandulosum Coleb., Verbenaceae, leaves (FECG on alteration in lipid and cholesterol metabolism in high fat diet fed hyperlipidemic rats. Plasma and hepatic lipid profiles, lipid and cholesterol metabolizing enzymes in target tissues and fecal total lipids and bile acid contents were evaluated in FECG treated normolipidemic and hyperlipidemic rats. These results were compared with synthetic hypolipidemic drug Lovastatin (LVS. Results indicate that FECG was able to positively regulate induced experimental hyperlipidemia by significant alteration in plasma and tissue lipid profiles. These results can be attributed to reduced absorption, effective elimination and augmented catabolism of lipids and cholesterol possibly due to high content of saponin and phytosterols in C. glandulosum. Use of C. glandulosum extract as a potential therapeutic agent against hypercholesterolemia and hypertriglyceridemia is indicated.

CD82 endocytosis and cholesterol-dependent reorganization of tetraspanin webs and lipid rafts

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Xu, Congfeng; Zhang, Yanhui H.; Thangavel, Muthusamy; Richardson, Mekel M.; Liu, Li; Zhou, Bin; Zheng, Yi; Ostrom, Rennolds S.; Zhang, Xin A.

2009-01-01

Tetraspanin CD82 suppresses cell migration, tumor invasion, and tumor metastasis. To determine the mechanism by which CD82 inhibits motility, most studies have focused on the cell surface CD82, which forms tetraspanin-enriched microdomains (TEMs) with other transmembrane proteins, such as integrins. In this study, we found that CD82 undergoes endocytosis and traffics to endosomes and lysosomes. To determine the endocytic mechanism of CD82, we demonstrated that dynamin and clathrin are not essential for CD82 internalization. Depletion or sequestration of sterol in the plasma membrane markedly inhibited the endocytosis of CD82. Despite the demand on Cdc42 activity, CD82 endocytosis is distinct from macropinocytosis and the documented dynamin-independent pinocytosis. As a TEM component, CD82 reorganizes TEMs and lipid rafts by redistributing cholesterol into these membrane microdomains. CD82-containing TEMs are characterized by the cholesterol-containing microdomains in the extreme light- and intermediate-density fractions. Moreover, the endocytosis of CD82 appears to alleviate CD82-mediated inhibition of cell migration. Taken together, our studies demonstrate that lipid-dependent endocytosis drives CD82 trafficking to late endosomes and lysosomes, and CD82 reorganizes TEMs and lipid rafts through redistribution of cholesterol.—Xu, C., Zhang, Y. H., Thangavel, M., Richardson, M. M., Liu, L., Zhou, B., Zheng, Y., Ostrom, R. S., Zhang, X. A. CD82 endocytosis and cholesterol-dependent reorganization of tetraspanin webs and lipid rafts. PMID:19497983

Cholesterol accumulation in Niemann Pick type C (NPC) model cells causes a shift in APP localization to lipid rafts

International Nuclear Information System (INIS)

Kosicek, Marko; Malnar, Martina; Goate, Alison; Hecimovic, Silva

2010-01-01

It has been suggested that cholesterol may modulate amyloid-β (Aβ) formation, a causative factor of Alzheimer's disease (AD), by regulating distribution of the three key proteins in the pathogenesis of AD (β-amyloid precursor protein (APP), β-secretase (BACE1) and/or presenilin 1 (PS1)) within lipid rafts. In this work we tested whether cholesterol accumulation upon NPC1 dysfunction, which causes Niemann Pick type C disease (NPC), causes increased partitioning of APP into lipid rafts leading to increased CTF/Aβ formation in these cholesterol-rich membrane microdomains. To test this we used CHO NPC1 -/- cells (NPC cells) and parental CHOwt cells. By sucrose density gradient centrifugation we observed a shift in fl-APP/CTF compartmentalization into lipid raft fractions upon cholesterol accumulation in NPC vs. wt cells. Furthermore, γ-secretase inhibitor treatment significantly increased fl-APP/CTF distribution in raft fractions in NPC vs. wt cells, suggesting that upon cholesterol accumulation in NPC1-null cells increased formation of APP-CTF and its increased processing towards Aβ occurs in lipid rafts. Our results support that cholesterol overload, such as in NPC disease, leads to increased partitioning of APP/CTF into lipid rafts resulting in increased amyloidogenic processing of APP in these cholesterol-rich membranes. This work adds to the mechanism of the cholesterol-effect on APP processing and the pathogenesis of Alzheimer's disease and supports the role of lipid rafts in these processes.

Localization of the placental BCRP/ABCG2 transporter to lipid rafts: Role for cholesterol in mediating efflux activity.

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Szilagyi, John T; Vetrano, Anna M; Laskin, Jeffrey D; Aleksunes, Lauren M

2017-07-01

The breast cancer resistance protein (BCRP/ABCG2) is an efflux transporter in the placental barrier. By transporting chemicals from the fetal to the maternal circulation, BCRP limits fetal exposure to a range of drugs, toxicants, and endobiotics such as bile acids and hormones. The purpose of the present studies was to 1) determine whether BCRP localizes to highly-ordered, cholesterol-rich lipid raft microdomains in placenta microvillous membranes, and 2) determine the impact of cholesterol on BCRP-mediated placental transport in vitro. BCRP expression was analyzed in lipid rafts isolated from placentas from healthy, term pregnancies and BeWo trophoblasts by density gradient ultracentrifugation. BeWo cells were also tested for their ability to efflux BCRP substrates after treatment with the cholesterol sequestrant methyl-β-cyclodextrin (MβCD, 5 mM, 1 h) or the cholesterol synthesis inhibitor pravastatin (200 μM, 48 h). BCRP was found to co-localize with lipid raft proteins in detergent-resistant, lipid raft-containing fractions from placental microvillous membranes and BeWo cells. Treatment of BeWo cells with MβCD redistributed BCRP protein into higher density non-lipid raft fractions. Repletion of the cells with cholesterol restored BCRP localization to lipid raft-containing fractions. Treatment of BeWo cells with MβCD or pravastatin increased cellular retention of two BCRP substrates, the fluorescent dye Hoechst 33342 and the mycotoxin zearalenone. Repletion with cholesterol restored BCRP transporter activity. Taken together, these data demonstrate that cholesterol may play a critical role in the post-translational regulation of BCRP in placental lipid rafts. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ocimum basilicum ethanolic extract decreases cholesterol synthesis and lipid accumulation in human macrophages.

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Bravo, Elena; Amrani, Souliman; Aziz, Mohammed; Harnafi, Hicham; Napolitano, Mariarosaria

2008-12-01

Macrophage lipid accumulation induced by low density lipoproteins (LDL) plays a pivotal role in atherosclerotic plaque development. Previous work showed that Ocimum basilicum extract, used as hypocholesterolemic agent by traditional medicine in Morocco, has hypolipidemic activity in rat acute hyperlipimidemia. This study investigated the effects of ethanolic extract of O. basilicum on lipid accumulation in human macrophages. As modification of LDL increase atherogenicity of the particles we evaluated the effects of the extract on LDL oxidation. The extract caused a dose-related increase of LDL-resistance to Cu(2+)-induced oxidation. Furthermore, at the dose of 60 microg/ml, significantly decreases the accumulation of macrophage lipid droplets induced by modified LDL evaluated as by red-oil staining. Cholesterol esterification and triacylglycerol synthesis in the cells were not affected. Macrophage treatment with 60 microg/ml, but not 20 microg/ml, of the extract reduced newly synthesized unesterified cholesterol by about 60% and decreased scavenger receptors activity by about 20-30%, evaluated by the internalization of cholesterol carried by [(3)H]CE-aggregated-LDL. The results suggest that O. basilicum ethanolic extract has the capability to reduce foam cell formation through the reduction of cholesterol synthesis and the modulation of the activity of surface scavenger receptors.

Lipid-lowering effect of bergamot polyphenolic fraction: role of pancreatic cholesterol ester hydrolase.

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Musolino, V; Gliozzi, M; Carresi, C; Maiuolo, J; Mollace, R; Bosco, F; Scarano, F; Scicchitano, M; Maretta, A; Palma, E; Iannone, M; Morittu, V M; Gratteri, S; Muscoli, C; Fini, M; Mollace, V

2017-01-01

Bergamot polyphenolic fraction (BPF) has been shown to positively modulate several mechanisms involved in metabolic syndrome, suggesting its use in therapy. In particular, it is able to induce a significant amelioration of serum lipid profile in hyperlipemic patients at different levels. The purpose of our study was to investigate the effect of BPF on cholesterol absorption physiologically mediated by pancreatic cholesterol ester hydrolase (pCEH). An in vitro activity assay was performed to study the effect of BPF on pCEH, whereas the rate of cholesterol absorption was evaluated through in vivo studies. In particular, male, Sprague-Dawley rats (200–225 g) were fed either normal chow or chow supplemented with 0.5% cholic acid, 5.5% peanut oil, and varying amounts of cholesterol (0 to 1.5%). BPF (10 mg/Kg) was daily administrated by means of a gastric gavage to animals fed with lipid supplemented diet for 4 weeks and, at the end of the study, plasma lipids and liver cholesteryl esters were measured in all experimental groups. Our results show that BPF was able to inhibit pCEH activity and this effect was confirmed, in vivo, via detection of lymphatic cholesteryl ester in rats fed with a cholesterol-rich diet. This evidence clarifies a further mechanism responsible for the hypolipemic properties of BPF previously observed in humans, confirming its beneficial effect in the therapy of hypercholesterolemia and in the treatment of metabolic syndrome.

Lipids rich in phosphatidylethanolamine from natural gas-utilizing bacteria reduce plasma cholesterol and classes of phospholipids

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Müller, H.; Hellgren, Lars; Olsen, E.

2004-01-01

-utilizing bacteria (LNGB), which were rich in PE. The group with 0% LNGB was fed a diet for which the lipid content was 100% soybean oil. The total cholesterol, LDL cholesterol, and HDL cholesterol of animals consuming a diet with 67% LNGB (67LNGB-diet), were significantly lowered by 35, 49, and 29%, respectively......, and unesterified cholesterol increased by 17% compared with the animals fed a diet of 100% lipids from soybean oil (SB-diet). In addition, the ratio of LDL cholesterol to HDL cholesterol was 27% lower in mink fed the 67LNGB-diet than those fed the S13-cliet. When the mink were fed the 67LNGB-diet, plasma PC, total...... phospholipids, lysoPC, and PI were lowered significantly compared with the mink fed a SB-diet. Plasma total cholesterol was correlated with total phospholipids as well as with PC (R = 0.8, P

Cholesterol: a novel regulatory role in myelin formation.

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Saher, Gesine; Quintes, Susanne; Nave, Klaus-Armin

2011-02-01

Myelin consists of tightly compacted membranes that form an insulating sheath around axons. The function of myelin for rapid saltatory nerve conduction is dependent on its unique composition, highly enriched in glycosphingolipids and cholesterol. Cholesterol emerged as the only integral myelin component that is essential and rate limiting for the development of CNS and PNS myelin. Experiments with conditional mouse mutants that lack cholesterol biosynthesis in oligodendrocytes revealed that only minimal changes of the CNS myelin lipid composition are tolerated. In Schwann cells of the PNS, protein trafficking and myelin compaction depend on cholesterol. In this review, the authors summarize the role of cholesterol in myelin biogenesis and myelin disease.

Impact of a 12-week high-intensity interval training without caloric restriction on body composition and lipid profile in sedentary healthy overweight/obese youth.

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Khammassi, Marwa; Ouerghi, Nejmeddine; Hadj-Taieb, Sameh; Feki, Moncef; Thivel, David; Bouassida, Anissa

2018-02-01

Although High-intensity interval training (HIIT) has shown its effectiveness in improving body composition, cardio-respiratory fitness and lipid profile in obese adults, evidences remain limited in overweight/obese youth. This study was conducted to investigate the effect of a 12-week HIIT program without caloric restriction on body composition and lipid profile among young overweight/obese men. Twenty healthy obese youth were randomly allocated into two groups; experimental group (HIIT) and control group. The HIIT program consisted in 3 exercises sessions per week (30 sec of work at 100% maximal aerobic velocity [MAV]) interspersed by 30 sec of active recovery at 50% MAV, starting by 15 repetitions to reach 27 by the end of the program. Aerobic capacity (MAV and maximum oxygen uptake [VO2max]), body composition (body mass index [BMI], waist circumference [WC], and fat mass percent) and lipid profile (triglycerides [TG] and total, high-density lipoprotein [HDL] and low-density lipoprotein [LDL] cholesterol) were determined before and after the HIIT program. Following 12 weeks of HIIT, WC, BMI ( P HIIT group, only. Total cholesterol ( P HIIT group, while LDL and HDL cholesterol levels remained unchanged in both groups. HIIT may be particularly useful in overweight/obese youth to improve body composition, aerobic fitness and lipid profile.

High-dose recombinant apolipoprotein A-I(milano) mobilizes tissue cholesterol and rapidly reduces plaque lipid and macrophage content in apolipoprotein e-deficient mice. Potential implications for acute plaque stabilization.

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Shah, P K; Yano, J; Reyes, O; Chyu, K Y; Kaul, S; Bisgaier, C L; Drake, S; Cercek, B

2001-06-26

Repeated doses of recombinant apolipoprotein A-I(Milano) phospholipid complex (apoA-I(m)) reduce atherosclerosis and favorably change plaque composition in rabbits and mice. In this study, we tested whether a single high dose of recombinant apoA-I(m) could rapidly mobilize tissue cholesterol and reduce plaque lipid and macrophage content in apoE-deficient mice. High cholesterol-fed, 26-week-old apoE-deficient mice received a single intravenous injection of saline (n=16), 1080 mg/kg dipalmitoylphosphatidylcholine (DPPC; n=14), or 400 mg/kg of recombinant apoA-I(m) complexed with DPPC (1:2.7 weight ratio; n=18). Blood was sampled before and 1 and 48 hours after injection, and aortic root plaques were evaluated for lipid content and macrophage content after oil-red O and immunostaining, respectively. One hour after injection, the plasma cholesterol efflux-promoting capacity was nearly 2-fold higher in recombinant apoA-I(m)-treated mice compared with saline and DPPC-treated mice (P<0.01). Compared with baseline values, serum free cholesterol, an index of tissue cholesterol mobilization, increased 1.6-fold by 1 hour after recombinant apoA-I(m) injection, and it remained significantly elevated at 48 hours (P<0.01). Mice receiving recombinant apoA-I(m) had 40% to 50% lower lipid content (P<0.01) and 29% to 36% lower macrophage content (P<0.05) in their plaques compared with the saline- and DPPC-treated mice, respectively. A single high dose of recombinant apoA-I(m) rapidly mobilizes tissue cholesterol and reduces plaque lipid and macrophage content in apoE-deficient mice. These findings suggest that this strategy could rapidly change plaque composition toward a more stable phenotype.

The Endoplasmic Reticulum Coat Protein II Transport Machinery Coordinates Cellular Lipid Secretion and Cholesterol Biosynthesis*

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Fryer, Lee G. D.; Jones, Bethan; Duncan, Emma J.; Hutchison, Claire E.; Ozkan, Tozen; Williams, Paul A.; Alder, Olivia; Nieuwdorp, Max; Townley, Anna K.; Mensenkamp, Arjen R.; Stephens, David J.; Dallinga-Thie, Geesje M.; Shoulders, Carol C.

2014-01-01

Triglycerides and cholesterol are essential for life in most organisms. Triglycerides serve as the principal energy storage depot and, where vascular systems exist, as a means of energy transport. Cholesterol is essential for the functional integrity of all cellular membrane systems. The endoplasmic reticulum is the site of secretory lipoprotein production and de novo cholesterol synthesis, yet little is known about how these activities are coordinated with each other or with the activity of the COPII machinery, which transports endoplasmic reticulum cargo to the Golgi. The Sar1B component of this machinery is mutated in chylomicron retention disorder, indicating that this Sar1 isoform secures delivery of dietary lipids into the circulation. However, it is not known why some patients with chylomicron retention disorder develop hepatic steatosis, despite impaired intestinal fat malabsorption, and why very severe hypocholesterolemia develops in this condition. Here, we show that Sar1B also promotes hepatic apolipoprotein (apo) B lipoprotein secretion and that this promoting activity is coordinated with the processes regulating apoB expression and the transfer of triglycerides/cholesterol moieties onto this large lipid transport protein. We also show that although Sar1A antagonizes the lipoprotein secretion-promoting activity of Sar1B, both isoforms modulate the expression of genes encoding cholesterol biosynthetic enzymes and the synthesis of cholesterol de novo. These results not only establish that Sar1B promotes the secretion of hepatic lipids but also adds regulation of cholesterol synthesis to Sar1B's repertoire of transport functions. PMID:24338480

Effect of Galactosylceramide on the Dynamics of Cholesterol-Rich Lipid Membranes

DEFF Research Database (Denmark)

Hall, A.; Rog, T.; Vattulainen, I.

2011-01-01

We use atom-scale molecular dynamics simulations to clarify the role of glycosphingolipids in the dynamics of cholesterol-rich lipid rafts. To this end, we consider lipid membranes that contain varying. amounts of galactosylceramide (GalCer), sphingomyelin, cholesterol, and phosphatidylcholine....... The results indicate that increasing the portion of GalCer molecules greatly slows down the lateral diffusion, Only 5-10 mol % of GalCer causes a decrease of almost an order of magnitude compared to corresponding membranes without GalCer. The slowing down is not related to interdigitation, which becomes...... weaker with increasing GalCer concentration. Instead, the decrease in diffusion is found to correlate with the increasing number of hydrogen bonds formed between GalCer and the phospholipid molecules, which is also observed to have other effects, such as to increase the friction between the membrane...

High Temperature- and High Pressure-Processed Garlic Improves Lipid Profiles in Rats Fed High Cholesterol Diets

Science.gov (United States)

Sohn, Chan Wok; Kim, Hyunae; You, Bo Ram; Kim, Min Jee; Kim, Hyo Jin; Lee, Ji Yeon; Sok, Dai-Eun; Kim, Jin Hee; Lee, Kun Jong

2012-01-01

Abstract Garlic protects against degenerative diseases such as hyperlipidemia and cardiovascular diseases. However, raw garlic has a strong pungency, which is unpleasant. In this study, we examined the effect of high temperature/high pressure-processed garlic on plasma lipid profiles in rats. Sprague–Dawley rats were fed a normal control diet, a high cholesterol (0.5% cholesterol) diet (HCD) only, or a high cholesterol diet supplemented with 0.5% high temperature/high pressure-processed garlic (HCP) or raw garlic (HCR) for 10 weeks. The body weights of the rats fed the garlic-supplemented diets decreased, mostly because of reduced fat pad weights. Plasma levels of total cholesterol (TC), low-density lipoprotein cholesterol, and triglyceride (TG) in the HCP and HCR groups decreased significantly compared with those in the HCD group. Additionally, fecal TC and TG increased significantly in the HCP and HCR groups. It is notable that no significant differences in plasma or fecal lipid profiles were observed between the HCP and HCR groups. High temperature/high pressure-processed garlic contained a higher amount of S-allyl cysteine than raw garlic (Pgarlic may be useful as a functional food to improve lipid profiles. PMID:22404600

Cholesterol catalyses Aβ42 aggregation through a heterogeneous nucleation pathway in the presence of lipid membranes

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Habchi, Johnny; Chia, Sean; Galvagnion, Céline; Michaels, Thomas C. T.; Bellaiche, Mathias M. J.; Ruggeri, Francesco Simone; Sanguanini, Michele; Idini, Ilaria; Kumita, Janet R.; Sparr, Emma; Linse, Sara; Dobson, Christopher M.; Knowles, Tuomas P. J.; Vendruscolo, Michele

2018-06-01

Alzheimer's disease is a neurodegenerative disorder associated with the aberrant aggregation of the amyloid-β peptide. Although increasing evidence implicates cholesterol in the pathogenesis of Alzheimer's disease, the detailed mechanistic link between this lipid molecule and the disease process remains to be fully established. To address this problem, we adopt a kinetics-based strategy that reveals a specific catalytic role of cholesterol in the aggregation of Aβ42 (the 42-residue form of the amyloid-β peptide). More specifically, we demonstrate that lipid membranes containing cholesterol promote Aβ42 aggregation by enhancing its primary nucleation rate by up to 20-fold through a heterogeneous nucleation pathway. We further show that this process occurs as a result of cooperativity in the interaction of multiple cholesterol molecules with Aβ42. These results identify a specific microscopic pathway by which cholesterol dramatically enhances the onset of Aβ42 aggregation, thereby helping rationalize the link between Alzheimer's disease and the impairment of cholesterol homeostasis.

Lipid composition of microdomains is altered in neuronopathic Gaucher disease sheep brain and spleen.

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Hein, Leanne K; Rozaklis, Tina; Adams, Melissa K; Hopwood, John J; Karageorgos, Litsa

2017-07-01

Gaucher disease is a lysosomal storage disorder caused by a deficiency in glucocerebrosidase activity that leads to accumulation of glucosylceramide and glucosylsphingosine. Membrane raft microdomains are discrete, highly organized microdomains with a unique lipid composition that provide the necessary environment for specific protein-lipid and protein-protein interactions to take place. In this study we purified detergent resistant membranes (DRM; membrane rafts) from the occipital cortex and spleen from sheep affected with acute neuronopathic Gaucher disease and wild-type controls. We observed significant increases in the concentrations of glucosylceramide, hexosylsphingosine, BMP and gangliosides and decreases in the percentage of cholesterol and phosphatidylcholine leading to an altered DRM composition. Altered sphingolipid/cholesterol homeostasis would dramatically disrupt DRM architecture making them less ordered and more fluid. In addition, significant changes in the length and degree of lipid saturation within the DRM microdomains in the Gaucher brain were also observed. As these DRM microdomains are involved in many cellular events, an imbalance or disruption of the cell membrane homeostasis may impair normal cell function. This disruption of membrane raft microdomains and imbalance within the environment of cellular membranes of neuronal cells may be a key factor in initiating a cascade process leading to neurodegeneration. Copyright © 2017 Elsevier Inc. All rights reserved.

Vesicle Origami and the Influence of Cholesterol on Lipid Packing.

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Tanasescu, Radu; Lanz, Martin A; Mueller, Dennis; Tassler, Stephanie; Ishikawa, Takashi; Reiter, Renate; Brezesinski, Gerald; Zumbuehl, Andreas

2016-05-17

The artificial phospholipid Pad-PC-Pad was analyzed in 2D (monolayers at the air/water interface) and 3D (aqueous lipid dispersions) systems. In the gel phase, the two leaflets of a Pad-PC-Pad bilayer interdigitate completely, and the hydrophobic bilayer region has a thickness comparable to the length of a single phospholipid acyl chain. This leads to a stiff membrane with no spontaneous curvature. Forced into a vesicular structure, Pad-PC-Pad has faceted geometry, and in its extreme form, tetrahedral vesicles were found as predicted a decade ago. Above the main transition temperature, a noninterdigitated Lα phase with fluid chains has been observed. The addition of cholesterol leads to a slight decrease of the main transition temperature and a gradual decrease in the transition enthalpy until the transition vanishes at 40 mol % cholesterol in the mixture. Additionally, cholesterol pulls the chains apart, and a noninterdigitated gel phase is observed. In monolayers, cholesterol has an ordering effect on liquid-expanded phases and disorders condensed phases. The wavenumbers of the methylene stretching vibration indicate the formation of a liquid-ordered phase in mixtures with 40 mol % cholesterol.

Differential dynamic and structural behavior of lipid-cholesterol domains in model membranes.

Directory of Open Access Journals (Sweden)

Luis F Aguilar

Full Text Available Changes in the cholesterol (Chol content of biological membranes are known to alter the physicochemical properties of the lipid lamella and consequently the function of membrane-associated enzymes. To characterize these changes, we used steady-state and time resolved fluorescence spectroscopy and two photon-excitation microscopy techniques. The membrane systems were chosen according to the techniques that were used: large unilamellar vesicles (LUVs for cuvette and giant unilamellar vesicles (GUVs for microscopy measurements; they were prepared from dipalmitoyl phosphatidylcholine (DPPC and dioctadecyl phosphatidylcholine (DOPC in mixtures that are well known to form lipid domains. Two fluorescent probes, which insert into different regions of the bilayer, were selected: 1,6-diphenyl-1,3,5-hexatriene (DPH was located at the deep hydrophobic core of the acyl chain regions and 2-dimethylamino-6-lauroylnaphthalene (Laurdan at the hydrophilic-hydrophobic membrane interface. Our spectroscopy results show that (i the changes induced by cholesterol in the deep hydrophobic phospholipid acyl chain domain are different from the ones observed in the superficial region of the hydrophilic-hydrophobic interface, and these changes depend on the state of the lamella and (ii the incorporation of cholesterol into the lamella induces an increase in the orientation dynamics in the deep region of the phospholipid acyl chains with a corresponding decrease in the orientation at the region close to the polar lipid headgroups. The microscopy data from DOPC/DPPC/Chol GUVs using Laurdan generalized polarization (Laurdan GP suggest that a high cholesterol content in the bilayer weakens the stability of the water hydrogen bond network and hence the stability of the liquid-ordered phase (Lo.

The effect of fish oil enriched margarine on plasma lipids, low density lipoprotein particle composition, size and susceptibility to oxidation

DEFF Research Database (Denmark)

Nielsen, Nina Skall; Marckmann, Peter; Høy, Carl-Erik

1998-01-01

We investigated the effect of incorporating n-3 polyunsaturated fatty acids (PUFAs) into the diet on the lipid-class composition of LDLs, their size, and their susceptibility to oxidation. Forty-seven healthy volunteers incorporated 30 g sunflower-oil (SO) margarine/d into their habitual diet...... during a 3-wk run-in period and then used either SQ or a fish-oil-enriched sunflower oil (FO) margarine for the following 4 wk. Plasma concentrations of total cholesterol, triacylglycerols, HDL cholesterol, LDL cholesterol, and apolipoproteins A-I and B did not differ significantly between the groups...... to 86 min, P = 0.003) and lower maximum rate of oxidation (from 10.5 to 10.2 nmol.mg(-1).min(-1), P = 0.003) after intake of the FO margarine. The results indicate that consumption of the FO compared with the SO margarine had no effect on LDL size and lipid composition and led to minor changes in LDL...

Childhood obesity treatment; Effects on BMI SDS, body composition, and fasting plasma lipid concentrations.

Science.gov (United States)

Nielsen, Tenna Ruest Haarmark; Fonvig, Cilius Esmann; Dahl, Maria; Mollerup, Pernille Maria; Lausten-Thomsen, Ulrik; Pedersen, Oluf; Hansen, Torben; Holm, Jens-Christian

2018-01-01

The body mass index (BMI) standard deviation score (SDS) may not adequately reflect changes in fat mass during childhood obesity treatment. This study aimed to investigate associations between BMI SDS, body composition, and fasting plasma lipid concentrations at baseline and during childhood obesity treatment. 876 children and adolescents (498 girls) with overweight/obesity, median age 11.2 years (range 1.6-21.7), and median BMI SDS 2.8 (range 1.3-5.7) were enrolled in a multidisciplinary outpatient treatment program and followed for a median of 1.8 years (range 0.4-7.4). Height and weight, body composition measured by dual-energy X-ray absorptiometry, and fasting plasma lipid concentrations were assessed at baseline and at follow-up. Lipid concentrations (total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), non-HDL, and triglycerides (TG)) were available in 469 individuals (264 girls). Linear regressions were performed to investigate the associations between BMI SDS, body composition indices, and lipid concentrations. At baseline, BMI SDS was negatively associated with concentrations of HDL (p = 6.7*10-4) and positively with TG (p = 9.7*10-6). Reductions in BMI SDS were associated with reductions in total body fat percentage (pobesity during multidisciplinary childhood obesity treatment are accompanied by improvements in body composition and fasting plasma lipid concentrations. Even in individuals increasing their BMI SDS, body composition and lipid concentrations may improve.

Ontogeny of Sex-Related Differences in Foetal Developmental Features, Lipid Availability and Fatty Acid Composition

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Consolacion Garcia-Contreras

2017-05-01

Full Text Available Sex-related differences in lipid availability and fatty acid composition during swine foetal development were investigated. Plasma cholesterol and triglyceride concentrations in the mother were strongly related to the adequacy or inadequacy of foetal development and concomitant activation of protective growth in some organs (brain, heart, liver and spleen. Cholesterol and triglyceride availability was similar in male and female offspring, but female foetuses showed evidence of higher placental transfer of essential fatty acids and synthesis of non-essential fatty acids in muscle and liver. These sex-related differences affected primarily the neutral lipid fraction (triglycerides, which may lead to sex-related postnatal differences in energy partitioning. These results illustrate the strong influence of the maternal lipid profile on foetal development and homeorhesis, and they confirm and extend previous reports that female offspring show better adaptive responses to maternal malnutrition than male offspring. These findings may help guide dietary interventions to ensure adequate fatty acid availability for postnatal development.

Interaction of cholesterol-conjugated ionizable amino lipids with biomembranes: lipid polymorphism, structure-activity relationship, and implications for siRNA delivery.

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Zhang, Jingtao; Fan, Haihong; Levorse, Dorothy A; Crocker, Louis S

2011-08-02

Delivery of siRNA is a major obstacle to the advancement of RNAi as a novel therapeutic modality. Lipid nanoparticles (LNP) consisting of ionizable amino lipids are being developed as an important delivery platform for siRNAs, and significant efforts are being made to understand the structure-activity relationship (SAR) of the lipids. This article uses a combination of small-angle X-ray scattering (SAXS) and differential scanning calorimetry (DSC) to evaluate the interaction between cholesterol-conjugated ionizable amino lipids and biomembranes, focusing on an important area of lipid SAR--the ability of lipids to destabilize membrane bilayer structures and facilitate endosomal escape. In this study, cholesterol-conjugated amino lipids were found to be effective in increasing the order of biomembranes and also highly effective in inducing phase changes in biological membranes in vitro (i.e., the lamellar to inverted hexagonal phase transition). The phase transition temperatures, determined using SAXS and DSC, serve as an indicator for ranking the potency of lipids to destabilize endosomal membranes. It was found that the bilayer disruption ability of amino lipids depends strongly on the amino lipid concentration in membranes. Amino lipids with systematic variations in headgroups, the extent of ionization, tail length, the degree of unsaturation, and tail asymmetry were evaluated for their bilayer disruption ability to establish SAR. Overall, it was found that the impact of these lipid structure changes on their bilayer disruption ability agrees well with the results from a conceptual molecular "shape" analysis. Implications of the findings from this study for siRNA delivery are discussed. The methods reported here can be used to support the SAR screening of cationic lipids for siRNA delivery, and the information revealed through the study of the interaction between cationic lipids and biomembranes will contribute significantly to the design of more efficient si

Lipid and cholesterol oxidation, color changes, and volatile compounds production in irradiated raw pork batters with different fat content

International Nuclear Information System (INIS)

Jo, Cheo Run; Byun, Myung Woo

2000-01-01

An emulsion-type product was prepared to determine the effect of irradiation on lipid and cholesterol oxidation, color change, and volatile production in raw pork with different fat content. Lipid oxidation increased with an increase in fat content or irradiation dose. Irradiated batters had higher cholesterol oxides than did non-irradiated batters, and the major cholesterol oxides formed in irradiated pork batters were 7α- and 7β- hydroxycholesterol. Hunter color a- and b-values of raw pork batters were decreased by irradiation regardless of fat content. Irradiation significantly increased the amount of volatile compounds. Although lipid oxidation of high fat products (10 and 15% fat) was higher than that of low fat products (4%), high fat products did not always produce greater amount of volatile compounds in raw pork batters. In summary, irradiation increased lipid and cholesterol oxidation, and volatile compounds production, and had detrimental effects on the color of raw pork batter under aerobic conditions

Lipidomic and proteomic analysis of Caenorhabditis elegans lipid droplets and identification of ACS-4 as a lipid droplet-associated protein

Energy Technology Data Exchange (ETDEWEB)

Vrablik, Tracy L. [Washington State Univ., Pullman, WA (United States); Petyuk, Vladislav A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Larson, Emily M. [Washington State Univ., Pullman, WA (United States); Smith, Richard D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Watts, Jennifer [Washington State Univ., Pullman, WA (United States)

2015-06-27

Lipid droplets are cytoplasmic organelles that store neutral lipids for membrane synthesis and energy reserves. In this study, we characterized the lipid and protein composition of purified C. elegans lipid droplets. These lipid droplets are composed mainly of triacylglycerols, surrounded by a phospholipid monolayer composed primarily of phosphatidylcholine and phosphatidylethanolamine. The fatty acid composition of the triacylglycerols was rich in fatty acid species obtained from the dietary E. coli, including cyclopropane fatty acids and cis-vaccenic acid. Unlike other organisms, C. elegans lipid droplets contain very little cholesterol or cholesterol esters. Comparison of the lipid droplet proteomes of wild type and high-fat daf-2 mutant strains shows a relative decrease of MDT-28 abundance in lipid droplets isolated from daf-2 mutants. Functional analysis of lipid droplet proteins identified in our proteomic studies indicated an enrichment of proteins required for growth and fat homeostasis in C. elegans.

Modeling the Effects of Lipid Composition on Stratum Corneum Bilayers Using Molecular Dynamics Simulations

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Huzil, J. Torin; Sivaloganathan, Siv; Kohandel, Mohammad; Foldvari, Marianna

2011-11-01

The advancement of dermal and transdermal drug delivery requires the development of delivery systems that are suitable for large protein and nucleic acid-based therapeutic agents. However, a complete mechanistic understanding of the physical barrier properties associated with the epidermis, specifically the membrane structures within the stratum corneum, has yet to be developed. Here, we describe the assembly and computational modeling of stratum corneum lipid bilayers constructed from varying ratios of their constituent lipids (ceramide, free fatty acids and cholesterol) to determine if there is a difference in the physical properties of stratum corneum compositions.

Anandamide Revisited: How Cholesterol and Ceramides Control Receptor-Dependent and Receptor-Independent Signal Transmission Pathways of a Lipid Neurotransmitter.

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Di Scala, Coralie; Fantini, Jacques; Yahi, Nouara; Barrantes, Francisco J; Chahinian, Henri

2018-05-22

Anandamide is a lipid neurotransmitter derived from arachidonic acid, a polyunsaturated fatty acid. The chemical differences between anandamide and arachidonic acid result in a slightly enhanced solubility in water and absence of an ionisable group for the neurotransmitter compared with the fatty acid. In this review, we first analyze the conformational flexibility of anandamide in aqueous and membrane phases. We next study the interaction of the neurotransmitter with membrane lipids and discuss the molecular basis of the unexpected selectivity of anandamide for cholesterol and ceramide from among other membrane lipids. We show that cholesterol behaves as a binding partner for anandamide, and that following an initial interaction mediated by the establishment of a hydrogen bond, anandamide is attracted towards the membrane interior, where it forms a molecular complex with cholesterol after a functional conformation adaptation to the apolar membrane milieu. The complex is then directed to the anandamide cannabinoid receptor (CB1) which displays a high affinity binding pocket for anandamide. We propose that cholesterol may regulate the entry and exit of anandamide in and out of CB1 by interacting with low affinity cholesterol recognition sites (CARC and CRAC) located in transmembrane helices. The mirror topology of cholesterol binding sites in the seventh transmembrane domain is consistent with the delivery, extraction and flip-flop of anandamide through a coordinated cholesterol-dependent mechanism. The binding of anandamide to ceramide illustrates another key function of membrane lipids which may occur independently of protein receptors. Interestingly, ceramide forms a tight complex with anandamide which blocks the degradation pathway of both lipids and could be exploited for anti-cancer therapies.

Effect of cholesterol feeding on tissue lipid perioxidation, glutathione peroxidase activity and liver microsomal functions in rats and guinea pigs

NARCIS (Netherlands)

TSAI, A. C.; THIE, G. M.; Lin, C. R.

1977-01-01

The effect of cholesterol feeding on liver and aortic nonenzymatic lipid peroxidation and glutathione peroxidase activities, and on liver microsomal NADPH-dependent lipid peroxidation, codeine hydroxylation and cytochrome P-450 levels was examined in rats and guinea pigs. One percent cholesterol was

Cholesterol Test

Science.gov (United States)

... artery disease. Other names for a cholesterol test: Lipid profile, Lipid panel What is it used for? If you ... Clinic [Internet]. Mayo Foundation for Medical Education and Research; c1998-2017.Cholesterol Test: Overview; 2016 Jan 12 [ ...

Transcriptional Regulation of T-Cell Lipid Metabolism: Implications for Plasma Membrane Lipid Rafts and T-Cell Function

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George A. Robinson

2017-11-01

Full Text Available It is well established that cholesterol and glycosphingolipids are enriched in the plasma membrane (PM and form signaling platforms called lipid rafts, essential for T-cell activation and function. Moreover, changes in PM lipid composition affect the biophysical properties of lipid rafts and have a role in defining functional T-cell phenotypes. Here, we review the role of transcriptional regulators of lipid metabolism including liver X receptors α/β, peroxisome proliferator-activated receptor γ, estrogen receptors α/β (ERα/β, and sterol regulatory element-binding proteins in T-cells. These receptors lie at the interface between lipid metabolism and immune cell function and are endogenously activated by lipids and/or hormones. Importantly, they regulate cellular cholesterol, fatty acid, glycosphingolipid, and phospholipid levels but are also known to modulate a broad spectrum of immune responses. The current evidence supporting a role for lipid metabolism pathways in controlling immune cell activation by influencing PM lipid raft composition in health and disease, and the potential for targeting lipid biosynthesis pathways to control unwanted T-cell activation in autoimmunity is reviewed.

Cholesterol and myelin biogenesis.

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Saher, Gesine; Simons, Mikael

2010-01-01

Myelin consists of several layers of tightly compacted membranes wrapped around axons in the nervous system. The main function of myelin is to provide electrical insulation around the axon to ensure the rapid propagation of nerve conduction. As the myelinating glia terminally differentiates, they begin to produce myelin membranes on a remarkable scale. This membrane is unique in its composition being highly enriched in lipids, in particular galactosylceramide and cholesterol. In this review we will summarize the role of cholesterol in myelin biogenesis in the central and peripheral nervous system.

Improved characterization of EV preparations based on protein to lipid ratio and lipid properties.

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Xabier Osteikoetxea

Full Text Available In recent years the study of extracellular vesicles has gathered much scientific and clinical interest. As the field is expanding, it is becoming clear that better methods for characterization and quantification of extracellular vesicles as well as better standards to compare studies are warranted. The goal of the present work was to find improved parameters to characterize extracellular vesicle preparations. Here we introduce a simple 96 well plate-based total lipid assay for determination of lipid content and protein to lipid ratios of extracellular vesicle preparations from various myeloid and lymphoid cell lines as well as blood plasma. These preparations included apoptotic bodies, microvesicles/microparticles, and exosomes isolated by size-based fractionation. We also investigated lipid bilayer order of extracellular vesicle subpopulations using Di-4-ANEPPDHQ lipid probe, and lipid composition using affinity reagents to clustered cholesterol (monoclonal anti-cholesterol antibody and ganglioside GM1 (cholera toxin subunit B. We have consistently found different protein to lipid ratios characteristic for the investigated extracellular vesicle subpopulations which were substantially altered in the case of vesicular damage or protein contamination. Spectral ratiometric imaging and flow cytometric analysis also revealed marked differences between the various vesicle populations in their lipid order and their clustered membrane cholesterol and GM1 content. Our study introduces for the first time a simple and readily available lipid assay to complement the widely used protein assays in order to better characterize extracellular vesicle preparations. Besides differentiating extracellular vesicle subpopulations, the novel parameters introduced in this work (protein to lipid ratio, lipid bilayer order, and lipid composition, may prove useful for quality control of extracellular vesicle related basic and clinical studies.

Cholesterol-based cationic lipids for gene delivery: contribution of molecular structure factors to physico-chemical and biological properties.

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Sheng, Ruilong; Luo, Ting; Li, Hui; Sun, Jingjing; Wang, Zhao; Cao, Amin

2014-04-01

In this work, we prepared a series of cholesterol-based cationic (Cho-cat) lipids bearing cholesterol hydrophobe, natural amino acid headgroups (lysine/histidine) and linkage (carbonate ester/ether) bonds. In which, the natural amino acid headgroups made dominant contribution to their physico-chemical and biological properties. Among the lipids, the l-lysine headgroup bearing lipids (Cho-es/et-Lys) showed higher pDNA binding affinity and were able to form larger sized and higher surface charged lipoplexes than that of l-histidine headgroup bearing lipids (Cho-es/et-His), they also demonstrated higher transfection efficacy and higher membrane disruption capacities than that of their l-histidine headgroup bearing counterparts. However, compared to the contributions of the headgroups, the (carbonate ester/ether) linkage bonds showed much less affects. Besides, it could be noted that, Cho-es/et-Lys lipids exhibited very high luciferase gene transfection efficiency that almost reached the transfection level of "gold standard" bPEI-25k, made them potential transfection reagents for practical application. Moreover, the results facilitated the understanding for the structure-activity relationship of the cholesterol-based cationic lipids, and also paved a simple and efficient way for achieving high transfection efficiency by modification of suitable headgroups on lipid gene carriers. Copyright © 2014 Elsevier B.V. All rights reserved.

[Levels of total lipids, cholesterol and progesterone during estrus synchronization and pregnancy in sheep].

Science.gov (United States)

Krajnicáková, M; Bekeová, E; Hendrichovský, V; Maracek, I

1993-01-01

Our investigations were concerned with dynamic changes in total lipids (CL), cholesterol (CHOL) and progesterone (P4) in blood serum of sheep in the period of oestrus synchronization treatment and during mating and gravidity. Our experiment was carried out using 10 animals housed under the conditions of productive rearing. Blood samples were taken from v. jugularis on day of swab application (day 0) and on days 3 and 7 of the action of Agelin vaginal swabs, on day of insemination, and on days 7, 14, 17 and in the 2nd, 3rd and 4th month of gravidity. Blood serum was used to determine total lipids and cholesterol by means of Bio-Lachema tests, and P4 concentrations employing RIA-test-Prog kits (URVJT, Kosice). A statistically significant decrease in concentrations of total lipids (Fig. 1, Tab. I) in sheep blood serum was recorded on day of insemination (P < 0.05) compared to day 0, with the value 1.59 +/- 0.31 g/l of serum, and in the 3rd month of gravidity (P < 0.01), at concentrations 1.36 +/- 0.38 g/l of serum. The determined decrease in their values in the mentioned period can be modulated by the mutually changing ratio of steroid hormones or by inhibition of synthesis of lipoproteins responsible for changes in total plasma lipids. Changes in cholesterol concentrations (Fig. 2, Tab. I) during the introduction of swabs were insignificant and ranged from 1.60 +/- 0.42 to 1.73 +/- 0.33 mmol/l of serum. An insignificant increase in cholesterol concentrations (P < 0.05), with its highest levels 1.98 +/- 0.43 mmol/l of serum, was recorded in the 3rd month of gravidity.(ABSTRACT TRUNCATED AT 250 WORDS)

Lipid transfers to HDL are diminished in long-term bedridden patients: association with low HDL-cholesterol and increased inflammatory markers.

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de Oliveira, Wilson Pascoalino Camargo; Tavoni, Thauany Martins; Freitas, Fatima Rodrigues; Silva, Bruna Miranda Oliveira; Maranhão, Raul Cavalcante

2017-08-01

Plasma lipids have been extensively studied in sedentary and in subjects practicing exercise training, but not in extreme inactivity as occurs in bedridden patients. This is important for the care of bedridden patients and understanding the overall plasma lipid regulation. Here, we investigated plasma lipids, lipid transfers to HDL and inflammatory markers in bedridden patients. Fasting blood samples were collected from 23 clinically stable bedridden patients under long-term care (>90 days) and 26 normolipidemic sedentary subjects, paired for age and gender. In vitro transfer of four lipids to HDL was performed by incubating plasma with donor nanoparticles containing radioactive lipids. Total (193 ± 36 vs 160 ± 43, p = 0.005), LDL (124 ± 3 vs 96 ± 33 p = 0.003) and HDL-cholesterol (45 ± 10 vs 36 ± 13, p = 0.008), apolipoprotein A-I (134 ± 20 vs 111 ± 24, p = 0.001) and oxidized LDL (53 ± 13 vs 43 ± 12, p = 0.011) were lower in bedridden patients, whereas triglycerides, apolipoprotein B, CETP and LCAT were equal in both groups. Transfers of all lipids, namely unesterified cholesterol, cholesterol esters, triglycerides and phospholipids, to HDL were lower in bedridden patients, probably due to their lower HDL-cholesterol levels. Concentrations of IL-1β, IL-6, IL-8, HGF and NGF were higher in bedridden patients compared to sedentary subjects. In conclusion, inactivity had great impact on HDL, by lowering HDL-cholesterol, apolipoprotein A-I and thereby cholesterol transfers to the lipoprotein, which suggests that inactivity may deteriorate HDL protection beyond the ordinary sedentary condition.

Induction of lipid peroxidation in erythrocytes during cholesterol oxidation catalyzed by cholesterol oxidase

International Nuclear Information System (INIS)

Kagan, V.E.; Monovich, O.; Ribarov, S.R.

1986-01-01

The authors study the ability of cholesterol oxidase (ChO), which catalyzes oxidation of cholesterol (Ch) to cholest-4-en-3-one and, at the same time, reduction of O 2 to H 2 O 2 , to induce the lipid peroxidation (LPO) in plasma membranes. Erythrocyte ghosts were obtained from guinea pig blood; the reaction of oxidation of Ch in the erythrocyte ghosts or in micelles with Triton X-100 was carried out in the following medium: Tris-HCl 0.2 M, pH 7.0 (at 37 C), Triton X-100 0.25%, and ChO 0.05 U/ml. At the present time ChO is often used to study the asymmetry of distribution of Ch in biomembranes and the velocity of its transbilayer migration. It is suggested that changes in membrane permeability do not take place during the reaction catalyzed by the enzyme, and no products capable of affecting flip-flop in biological are formed. Accumulation of LPO products in erythrocyte membranes discovered in this investigation under the influence of ChO compels critical re-examination of the resutls

Inward cholesterol gradient of the membrane system in P. falciparum-infected erythrocytes involves a dilution effect from parasite-produced lipids

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Fuyuki Tokumasu

2014-05-01

Full Text Available Plasmodium falciparum (Pf infection remodels the human erythrocyte with new membrane systems, including a modified host erythrocyte membrane (EM, a parasitophorous vacuole membrane (PVM, a tubulovesicular network (TVN, and Maurer's clefts (MC. Here we report on the relative cholesterol contents of these membranes in parasitized normal (HbAA and hemoglobin S-containing (HbAS, HbAS erythrocytes. Results from fluorescence lifetime imaging microscopy (FLIM experiments with a cholesterol-sensitive fluorophore show that membrane cholesterol levels in parasitized erythrocytes (pRBC decrease inwardly from the EM, to the MC/TVN, to the PVM, and finally to the parasite membrane (PM. Cholesterol depletion of pRBC by methyl-β-cyclodextrin treatment caused a collapse of this gradient. Lipid and cholesterol exchange data suggest that the cholesterol gradient involves a dilution effect from non-sterol lipids produced by the parasite. FLIM signals from the PVM or PM showed little or no difference between parasitized HbAA vs HbS-containing erythrocytes that differed in lipid content, suggesting that malaria parasites may regulate the cholesterol contents of the PVM and PM independently of levels in the host cell membrane. Cholesterol levels may affect raft structures and the membrane trafficking and sorting functions that support Pf survival in HbAA, HbAS and HbSS erythrocytes.

[Correction of lipid peroxidation and antioxidant system disorders by bioflavonoids during modeling of cholesterol atherosclerosis in rabbits].

Science.gov (United States)

Shysh, A M; Pashevin, D O; Dosenko, V Ie; Moĭbenko, O O

2011-01-01

We have studied the influence of bioflavonoids (quercetin, corvitin) on lipid peroxidation and antioxidant enzymes in the modeling of cholesterol atherosclerosis in rabbits. It has been shown that simultaneous administration of the quercetin derivative corvitin suppressed lipid peroxidation. We showed that under hypercholesterolemia, the concentration of malone dialdehyde in myocardial tissue in rabbits is significantly increased, while administration of bioflavonoids decreased the concentration of malone dialdehyde by 38.3%. Furthermore, corvitin caused activating effects on antioxidant enzymes superoxide dismutase and catalase in cardiac tissue. Our data suggest that bioflavonoids are able to suppress lipid peroxidation and prevent the decrease ofantioxidant enzymes activity in rabbits with cholesterol-rich diet induced atherosclerosis.

Influence of cholesterol and ceramide-VI on structure of the multilamellar lipid membrane at water exchange

International Nuclear Information System (INIS)

Ryabova, N.Yu.; Kiselev, M.A.; Balagurov, A.M.

2009-01-01

The results of neutron diffraction investigation of structure changes in multilamellar lipid membranes DPPC/cholesterol and DPPC/ceramide-VI (DPPC - dipalmitoylphosphatidylcholine) during the processes of hydration and dehydration are presented. The influence of cholesterol and ceramide-VI on kinetics of water exchange in DPPC membrane is characterized

Lipid composition of the stratum corneum and cutaneous water loss in birds along an aridity gradient.

Science.gov (United States)

Champagne, Alex M; Muñoz-Garcia, Agustí; Shtayyeh, Tamer; Tieleman, B Irene; Hegemann, Arne; Clement, Michelle E; Williams, Joseph B

2012-12-15

Intercellular and covalently bound lipids within the stratum corneum (SC), the outermost layer of the epidermis, are the primary barrier to cutaneous water loss (CWL) in birds. We compared CWL and intercellular SC lipid composition in 20 species of birds from desert and mesic environments. Furthermore, we compared covalently bound lipids with CWL and intercellular lipids in the lark family (Alaudidae). We found that CWL increases in birds from more mesic environments, and this increase was related to changes in intercellular SC lipid composition. The most consistent pattern that emerged was a decrease in the relative amount of cerebrosides as CWL increased, a pattern that is counterintuitive based on studies of mammals with Gaucher disease. Although covalently bound lipids in larks did not correlate with CWL, we found that covalently bound cerebrosides correlated positively with intercellular cerebrosides and intercellular cholesterol ester, and intercellular cerebrosides correlated positively with covalently bound free fatty acids. Our results led us to propose a new model for the organization of lipids in the avian SC, in which the sugar moieties of cerebrosides lie outside of intercellular lipid layers, where they may interdigitate with adjacent intercellular cerebrosides or with covalently bound cerebrosides.

Description of Discordance Between LDL Cholesterol, Non-HDL Cholesterol, and LDL Particle Number Among Patients of a Lipid Clinic

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Joshua W Gaborcik

2017-09-01

Full Text Available Background: While LDL cholesterol measures the cholesterol content within an LDL particle (LDL-P, it may not reflect LDL-P concentrations. If discordance exists, LDL-P may better predict cardiovascular events compared to LDL-C and non-HDL cholesterol (non-HDL-C. In primary prevention patients, discordance has been associated with diabetes, ethnicity, gender, metabolic syndrome, and smoking history. Objective: To describe discordance in patients of a lipid clinic by exploring associations between patient characteristics and discordance among LDL-C, non-HDL-C, or LDL-P. Secondarily to compare proportion of patients with baseline concordance versus discordance who have ASCVD events, diagnoses of new onset diabetes or death. Methods: A retrospective, single-center cohort study at a large academic medical center was conducted. Patients establishing care from January 2009 through December 2012 with complete initial labs were included. Logistic regression models were used to explore associations between discordance and patient characteristics. Results: Of 603 patients screened, the final cohort included 166 patients with 104 (62.7% discordant. LDL-P was the most common discordant value. Discordance was associated with gender, smoking status, use of lipid lowering medications, and achieving patient specific LDL-C goals. In terms of any event observed after initial measurements, no significant differences were detected between discordant and concordant groups. Conclusion: Within a lipid clinic population, discordance was associated with male gender, smoking status, lipid-lowering therapy, and being at patient specific LDL-C goal. While associations were found in our population, clinicians should consider measuring LDL-P to fully assess presence or extent of discordance. Conflict of Interest We declare no conflicts of interest or financial interests that the authors or members of their immediate families have in any product or service discussed in the

Cholesterol and polyunsaturated lipids working in concert to modulate G protein-coupled receptors

Czech Academy of Sciences Publication Activity Database

Javanainen, M.; Manna, M.; Vähäheikkilä, M.; Niemelä, M.; Tynkkynen, J.; Guixa-Gonzaléz, R.; Martinez-Seara, Hector; Enkavi, G.; Kulig, W.; Müller, D. J.; Rog, T.; Vattulainen, I.

2017-01-01

Roč. 46, Suppl 1 (2017), S47 ISSN 0175-7571. [IUPAB congress /19./ and EBSA congress /11./. 16.07.2017-20.07.2017, Edinburgh] Institutional support: RVO:61388963 Keywords : GPCR * cholesterol * lipids Subject RIV: BO - Biophysics

Cholesterol Bilayer Domains in the Eye Lens Health: A Review.

Science.gov (United States)

Widomska, Justyna; Subczynski, Witold K; Mainali, Laxman; Raguz, Marija

2017-12-01

The most unique biochemical characteristic of the eye lens fiber cell plasma membrane is its extremely high cholesterol content, the need for which is still unclear. It is evident, however, that the disturbance of Chol homeostasis may result in damages associated with cataracts. Electron paramagnetic resonance methods allow discrimination of two types of lipid domains in model membranes overloaded with Chol, namely, phospholipid-cholesterol domains and pure Chol bilayer domains. These domains are also detected in human lens lipid membranes prepared from the total lipids extracted from lens cortices and nuclei of donors from different age groups. Independent of the age-related changes in phospholipid composition, the physical properties of phospholipid-Chol domains remain the same for all age groups and are practically identical for cortical and nuclear membranes. The presence of Chol bilayer domains in these membranes provides a buffering capacity for cholesterol concentration in the surrounding phospholipid-Chol domains, keeping it at a constant saturating level and thus keeping the physical properties of the membrane consistent with and independent of changes in phospholipid composition. It seems that the presence of Chol bilayer domains plays an integral role in the regulation of cholesterol-dependent processes in fiber cell plasm membranes and in the maintenance of fiber cell membrane homeostasis.

Lipid composition of human meibum

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R. Schnetler

2013-12-01

Full Text Available The structure and function of meibomian gland lipids in the tear film are highly complex. Evidence shows that the precorneal tear film consists of discrete layers: the inner mucin layer, the middle aqueous layer and the outer lipid layer. In this review we focus on the outer, biphasic lipid layer of the tear film which consists of a ‘thick’ outer, non-polar layer  and a ‘thin’ inner, polar layer. We discuss the main composition of the polar and non-polar lipids within meibum (wax esters, cholesteryl esters, mono-, di- and tri-acylglycerols, ceramides, phospholipids  et cetera. We address the composition of meibomian lipids in subjects suffering from various ocular diseases in comparison with the composition in healthy individuals. Further analysis is needed to determine whether a correlation exists between the etiology of various ocular diseases and the fluctuation on the lipids as well as to establish whether or not tear lipid analysis can be used as a diagnostic tool.

The Effects of 8-Weeks Aerobic Exercise Program on Blood Lipids and Cholesterol Profile of Smokers vs. Non Smokers

Science.gov (United States)

Taifour, Akef; AL-Shishani, Ahmad; Khasawneh, Aman; AL-Nawaiseh, Ali; Bakeer, Mohammed

2015-01-01

The aim of this study was to compare the effects of 8-week aerobic exercise program on blood lipids and cholesterol profile of smoker's vs. non-smokers. A total of 34 male subjects (18 non-smokers and 16 smokers) took part in this study. Both groups were pre- and post tested in their blood-lipids and cholesterol profile before and after the 8-week…

Significance of sterol structural specificity : desmosterol cannot replace cholesterol in lipid rafts

NARCIS (Netherlands)

Vainio, S.; Jansen, Maurice; Koivusalo, M.; Róg, T.; Karttunen, M.E.J.; Vattulainen, I.; Ikonen, E.

2006-01-01

Desmosterol is an immediate precursor of cholesterol in the Bloch pathway of sterol synthesis and an abundant membrane lipid in specific cell types. The significance of the difference between the two sterols, an additional double bond at position C24 in the tail of desmosterol, is not known. Here,

Quantitative Analysis of Serum Lipid Profile in Gallstone Patients and Controls

International Nuclear Information System (INIS)

Channa, N.A.; Ghanghro, A.B.; Soomro, A.M.

2010-01-01

The present study was undertaken to explore the possible role of serum lipid profile in gallstone formation. For this serum lipid profile such as total, free and bound cholesterol, LDL cholesterol, HDL cholesterol, triacylglycerols and total lipids were determined in 109 gallstone patients and 100 controls (matched for age, sex and with negative personal or family history of gallstones) treated at Liaquat University Hospital, Jamshoro, Pakistan. Comparison for serum lipid profile between different groups of gallstone patients and controls revealed no significant variation except for the triacylglycerols and total lipids, which were differed significantly between females of up to 45 and above 45 years age. Comparison for serum lipid profile between pure cholesterol and mixed composition gallstone formers showed no significant difference (p>0.05) between the two groups. The serum lipid profile significantly varied between gallstone patients and controls except bound cholesterol level. Comparison of total cholesterol, free cholesterol, LDL cholesterol, HDL cholesterol, triacylglycerols and total lipids between gallstone patients and controls revealed that there was a significant difference between gallstone patients and controls for (a) females with or without gallstones, (b) females of up to 45 years age and (c) females having more than 3 children. HDL cholesterol is significantly decreased in all the groups of gallstone patients as compared to controls, whereas, bound cholesterol remained non significant in all the groups of gallstone patients when compared with controls. In conclusion, elevated serum total cholesterol, free cholesterol, LDL cholesterol, triacylglycerols and decreased levels of HDL cholesterol seem to play major contributing role in the pathogenesis of gallstones in females of up to 45 years age with more than three children. (author)

Childhood obesity treatment; Effects on BMI SDS, body composition, and fasting plasma lipid concentrations.

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Tenna Ruest Haarmark Nielsen

Full Text Available The body mass index (BMI standard deviation score (SDS may not adequately reflect changes in fat mass during childhood obesity treatment. This study aimed to investigate associations between BMI SDS, body composition, and fasting plasma lipid concentrations at baseline and during childhood obesity treatment.876 children and adolescents (498 girls with overweight/obesity, median age 11.2 years (range 1.6-21.7, and median BMI SDS 2.8 (range 1.3-5.7 were enrolled in a multidisciplinary outpatient treatment program and followed for a median of 1.8 years (range 0.4-7.4. Height and weight, body composition measured by dual-energy X-ray absorptiometry, and fasting plasma lipid concentrations were assessed at baseline and at follow-up. Lipid concentrations (total cholesterol (TC, low-density lipoprotein (LDL, high-density lipoprotein (HDL, non-HDL, and triglycerides (TG were available in 469 individuals (264 girls. Linear regressions were performed to investigate the associations between BMI SDS, body composition indices, and lipid concentrations.At baseline, BMI SDS was negatively associated with concentrations of HDL (p = 6.7*10-4 and positively with TG (p = 9.7*10-6. Reductions in BMI SDS were associated with reductions in total body fat percentage (p<2*10-16 and percent truncal body fat (p<2*10-16. Furthermore, reductions in BMI SDS were associated with improvements in concentrations of TC, LDL, HDL, non-HDL, LDL/HDL-ratio, and TG (all p <0.0001. Changes in body fat percentage seemed to mediate the changes in plasma concentrations of TC, LDL, and non-HDL, but could not alone explain the changes in HDL, LDL/HDL-ratio or TG. Among 81 individuals with available lipid concentrations, who increased their BMI SDS, 61% improved their body composition, and 80% improved their lipid concentrations.Reductions in the degree of obesity during multidisciplinary childhood obesity treatment are accompanied by improvements in body composition and fasting plasma

Stearoyl-CoA Desaturase 1 Is a Key Determinant of Membrane Lipid Composition in 3T3-L1 Adipocytes.

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Sergio Rodriguez-Cuenca

Full Text Available Stearoyl-CoA desaturase 1 (SCD1 is a lipogenic enzyme important for the regulation of membrane lipid homeostasis; dysregulation likely contributes to obesity associated metabolic disturbances. SCD1 catalyses the Δ9 desaturation of 12-19 carbon saturated fatty acids to monounsaturated fatty acids. To understand its influence in cellular lipid composition we investigated the effect of genetic ablation of SCD1 in 3T3-L1 adipocytes on membrane microdomain lipid composition at the species-specific level. Using liquid chromatography/electrospray ionisation-tandem mass spectrometry, we quantified 70 species of ceramide, mono-, di- and trihexosylceramide, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, bis(monoacylglycerophosphate, phosphatidylinositol and cholesterol in 3T3-L1 adipocytes in which a 90% reduction in scd1 mRNA expression was achieved with siRNA. Cholesterol content was unchanged although decreases in other lipids resulted in cholesterol accounting for a higher proportion of lipid in the membranes. This was associated with decreased membrane lateral diffusion. An increased ratio of 24:0 to 24:1 in ceramide, mono- and dihexosylceramide, and sphingomyelin likely also contributed to this decrease in lateral diffusion. Of particular interest, we observed a decrease in phospholipids containing arachidonic acid. Given the high degree of structural flexibility of this acyl chain this will influence membrane lateral diffusion, and is likely responsible for the transcriptional activation of Lands' cycle enzymes lpcat3 and mboat7. Of relevance these profound changes in the lipidome were not accompanied by dramatic changes in gene expression in mature differentiated adipocytes, suggesting that adaptive homeostatic mechanisms to ensure partial maintenance of the biophysical properties of membranes likely occur at a post-transcriptional level.

[Composition of chicken and quail eggs].

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Closa, S J; Marchesich, C; Cabrera, M; Morales, J C

1999-06-01

Qualified food composition data on lipids composition are needed to evaluate intakes as a risk factor in the development of heart disease. Proximal composition, cholesterol and fatty acid content of chicken and quail eggs, usually consumed or traded, were analysed. Proximal composition were determined using AOAC (1984) specific techniques; lipids were extracted by a Folch's modified technique and cholesterol and fatty acids were determined by gas chromatography. Results corroborate the stability of eggs composition. Cholesterol content of quail eggs is similar to chicken eggs, but it is almost the half content of data registered in Handbook 8. Differences may be attributed to the analytical methodology used to obtain them. This study provides data obtained with up-date analytical techniques and accessory information useful for food composition tables.

An isocratic HPLC method for the simultaneous determination of cholesterol, cardiolipin, and DOPC in lyophilized lipids and liposomal formulations.

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Simonzadeh, Ninus

2009-04-01

Phospholipids, such as 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), and 1,1',2,2'-tetramyristoyl cardiolipin, along with cholesterol, form liposomes in aqueous media and have been investigated at NeoPharm (Lake Bluff, IL) as drug-delivery systems. To accurately assess the effectiveness of various formulations involving the use of aforementioned phospholipids and cholesterol, their quantitative determination is essential. An isocratic high-performance liquid chromatographic method for the simultaneous determination of cholesterol, cardiolipin, and DOPC in various pharmaceutical formulations containing the active drug substance has consequently been developed and is presented here. The current method utilizes an ASTEC-diol analytical column and is shown to be stability-indicating and free from interference from any of the formulation excipients, such as sucrose, sodium chloride, and sodium lactate. The analytes are detected using an evaporative light scattering detector (Alltech or Polymer Laboratories). The quantitation of each lipid component is performed using non-linear regression analysis. The retention characteristics of the analytes are examined as a function of eluent composition (e.g., pH, salt content, organic to aqueous phase ratio) and column temperature. The method was validated and was found to be sensitive, specific, rugged, and cost-effective. The current method provides enhanced chromatographic separation for lipid components as well as degradation products as compared to similar methods reported in the literature. It is also inherently simpler than other similar methods reported in the literature that typically use complex gradient elution.

Synthesis and validation of novel cholesterol-based fluorescent lipids designed to observe the cellular trafficking of cationic liposomes.

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Kim, Bieong-Kil; Seu, Young-Bae; Choi, Jong-Soo; Park, Jong-Won; Doh, Kyung-Oh

2015-09-15

Cholesterol-based fluorescent lipids with ether linker were synthesized using NBD (Chol-E-NBD) or Rhodamine B (Chol-E-Rh), and the usefulnesses as fluorescent probes for tracing cholesterol-based liposomes were validated. The fluorescent intensities of liposomes containing these modified lipids were measured and observed under a microscope. Neither compound interfered with the expression of GFP plasmid, and live cell images were obtained without interferences. Changes in the fluorescent intensity of liposomes containing Chol-E-NBD were followed by flow cytometry for up to 24h. These fluorescent lipids could be useful probes for trafficking of cationic liposome-mediated gene delivery. Copyright © 2015 Elsevier Ltd. All rights reserved.

The fatty acid and cholesterol composition of enriched egg yolk lipids obtained by modifying hens’ diets with fish oil and flaxseed

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Yalçyn, Hasan

2007-12-01

Full Text Available The effects of fish oil and flaxseed in the diets of laying hens on the cholesterol and fatty acid composition of egg lipids were studied. Isa-White laying hens and five experimental diets were used. The first diet was used as the control. Fish oil (1.5%, flaxseed (4.32% and 8.64 or both of them (1.5% fish oil and 4.32% flaxseed were added to the others and hens were fed for 30 and 60 days. The cholesterol and fatty acid composition of the yolks were determined. No significant difference (pSe han estudiado los efectos producidos por la presencia de aceite de pescado y linaza, en la dieta de gallinas ponedoras, sobre la composición en colesterol y ácidos grasos de los lípidos del huevo. Se han utilizado gallinas ponedoras Isa-White y cinco tipos de dietas experimentales. La primera dieta fue usada como control. Se añadió aceite de pescado (1.5%, linaza (4.32% y 8.64 o ambos (1.5% aceite de pescado y 4.32% linaza a las otras dietas y se alimentó a las gallinas durante 30 y 60 días, determinándose la composición en colesterol y ácidos grasos de las yemas. No se encontró diferencia significativa (p<0.05 debida a las dietas en el contenido de colesterol de las yemas excepto en la que contenía 8.64% de linaza. El contenido total de ácidos grasos saturados disminuyó en todas las dietas en comparación con la dieta control. El contenido total de ácidos grasos n-3 fue significativamente mayor en todas las dietas. El cambio predominante en las dietas que contenían linaza se encontró en el contenido de ácido linolénico. El contenido de los ácidos eicosapentaenoico, docosapentaenoico y docosahexaenoico de todas las dietas fue significativamente mayor.

Postpartum weight retention is associated with elevated ratio of oxidized LDL lipids to HDL-cholesterol.

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Puhkala, Jatta; Luoto, Riitta; Ahotupa, Markku; Raitanen, Jani; Vasankari, Tommi

2013-12-01

Oxidized LDL lipids (ox-LDL) are associated with lifestyle diseases such as cardiovascular diseases, metabolic syndrome and type 2 diabetes. The present study investigated how postpartum weight retention effects on ox-LDL and serum lipids. The study is a nested comparative research of a cluster-randomized controlled trial, NELLI (lifestyle and counselling during pregnancy). During early pregnancy (8-12 weeks) and 1 year postpartum, 141 women participated in measurements for determining of plasma lipids: total cholesterol (T-C), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), triacylglycerols (TAG) and ox-LDL. Subjects were stratified into tertiles (weight loss, unaltered weight and weight gain groups) based on their weight change from baseline to follow-up. Ox-LDL was determined by baseline level of conjugated dienes in LDL lipids. Among the group of weight gainers, concentration of TAG reduced less (-0.14 vs. -0.33, p = 0.002), HDL-C reduced more (-0.31 vs. -0.16, p = 0.003) and ox-LDL/HDL-C ratio increased (3.0 vs. -0.2, p = 0.003) when compared to group of weight loss. Both T-C and LDL-C elevated more (0.14 vs. -0.21, p = 0.008; 0.31 vs. 0.07, p = 0.015) and TAG and ox-LDL reduced less (-0.33 vs. 0.20, p = 0.033; -3.33 vs. -0.68, p = 0.026) in unaltered weight group compared to weight loss group. The women who gained weight developed higher TAG and ox-LDL/HDL-C ratio as compared to those who lost weight. Postpartum weight retention of 3.4 kg or more is associated with atherogenic lipid profile.

2-heptyl-formononetin increases cholesterol and induces hepatic steatosis in mice

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Andersen, Charlotte; Schjoldager, Janne Gram; Tortzen, Christian

2013-01-01

Consumption of isoflavones may prevent adiposity, hepatic steatosis, and dyslipidaemia. However, studies in the area are few and primarily with genistein. This study investigated the effects of formononetin and its synthetic analogue, 2-heptyl-formononetin (C7F), on lipid and cholesterol metabolism...... in C57BL/6J mice. The mice were fed a cholesterol-enriched diet for five weeks to induce hypercholesterolemia and were then fed either the cholesterol-enriched diet or the cholesterol-enriched diet-supplemented formononetin or C7F for three weeks. Body weight and composition, glucose homeostasis......, and plasma lipids were compared. In another experiment, mice were fed the above diets for five weeks, and hepatic triglyceride accumulation and gene expression and histology of adipose tissue and liver were examined. Supplementation with C7F increased plasma HDL-cholesterol thereby increasing the plasma...

Interaction of AnxA6 with isolated and artificial lipid microdomains; importance of lipid composition and calcium content.

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Domon, Magdalena M; Besson, Françoise; Tylki-Szymanska, Anna; Bandorowicz-Pikula, Joanna; Pikula, Slawomir

2013-04-05

Niemann-Pick type C (NPC) disease is a lipid storage disorder characterized by accumulation of lipids in the late endosome/lysosome (LE/LY) compartment. In our previous report we isolated membranes of the LE/LY compartment from NPC L1 skin fibroblasts with a mutation in the NPC1 gene and found that they were characterized by low fluidity which likely contributed to the impaired function of membrane proteins involved in storage and turnover of cholesterol. In this report we isolated lipid microdomains (DRMs) from membranes of various cellular compartments and observed an increased amount of DRMs in the LE/LY compartment of NPC L1 cells in comparison to control cells, with no change in the DRM content in the plasma membrane. In addition, in the NPC cells, the majority of the cholesterol-interacting protein, AnxA6, which participates in the transport and distribution of cholesterol, translocated to DRMs upon a rise in Ca(2+) concentration. The mechanism of this translocation was further studied in vitro using Langmuir monolayers. We found that Ca(2+) is the main factor which regulates the interaction of AnxA6 with monolayers composed of neutral lipids, such as DPPC and sphingomyelin, and may also determine AnxA6 localization in cholesterol and sphingomyelin enriched microdomains, thus contributing to the etiology of the NPC disease.

Peroxisome proliferator-activated receptor ligands regulate lipid content, metabolism, and composition in fetal lungs of diabetic rats.

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Kurtz, M; Capobianco, E; Careaga, V; Martinez, N; Mazzucco, M B; Maier, M; Jawerbaum, A

2014-03-01

Maternal diabetes impairs fetal lung development. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors relevant in lipid homeostasis and lung development. This study aims to evaluate the effect of in vivo activation of PPARs on lipid homeostasis in fetal lungs of diabetic rats. To this end, we studied lipid concentrations, expression of lipid metabolizing enzymes and fatty acid composition in fetal lungs of control and diabetic rats i) after injections of the fetuses with Leukotriene B4 (LTB4, PPARα ligand) or 15deoxyΔ(12,14)prostaglandin J2 (15dPGJ2, PPARγ ligand) and ii) fed during pregnancy with 6% olive oil- or 6% safflower oil-supplemented diets, enriched with PPAR ligands were studied. Maternal diabetes increased triglyceride concentrations and decreased expression of lipid-oxidizing enzymes in fetal lungs of diabetic rats, an expression further decreased by LTB4 and partially restored by 15dPGJ2 in lungs of male fetuses in the diabetic group. In lungs of female fetuses in the diabetic group, maternal diets enriched with olive oil increased triglyceride concentrations and fatty acid synthase expression, while those enriched with safflower oil increased triglyceride concentrations and fatty acid transporter expression. Both olive oil- and safflower oil-supplemented diets decreased cholesterol and cholesteryl ester concentrations and increased the expression of the reverse cholesterol transporter ATP-binding cassette A1 in fetal lungs of female fetuses of diabetic rats. In fetal lungs of control and diabetic rats, the proportion of polyunsaturated fatty acids increased with the maternal diets enriched with olive and safflower oils. Our results revealed important changes in lipid metabolism in fetal lungs of diabetic rats, and in the ability of PPAR ligands to modulate the composition of lipid species relevant in the lung during the perinatal period.

Changes in lipid indices and body composition one year after laparoscopic gastrectomy: a prospective study.

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Lee, Soo Jin; Kim, Ji Young; Ha, Tae Kyung; Choi, Yun Young

2018-05-11

The purpose of this prospective study was to investigate changes in lipid indices associated with whole body composition during 1 year of follow-up after laparoscopic gastrectomy. Thirty-seven patients with benign and malignant gastric neoplasm who underwent laparoscopic gastrectomy were prospectively enrolled. None of the patients were treated with adjuvant chemotherapy. Lipid indices and body composition were measured preoperatively and at six and 12 months after laparoscopic gastrectomy. Lipid indices included total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). Body weight, fat and lean body mass (LBM) were measured by dual-energy X-ray absorptiometry and the change in fat and LBM in the trunk, arms and legs was compared. Body weight significantly decreased from 63.0 ± 11.1 kg preoperatively to 56.8 ± 10.6 kg 12 months after laparoscopic gastrectomy, with a mean of 7.1% (4.6 kg) weight loss. Fat and LBM loss contributed 68.4% (3.1 kg) and 30.1% (1.4 kg) of the total weight loss, respectively. In both the non-obese and obese groups, body weight, fat and LBM did not change significantly between 6 months and 12 months after gastrectomy. TC and LDL-C levels significantly decreased during the first six-month period and HDL-C significantly increased until 12 months after gastrectomy in the non-obese group. In the obese group, the degree of reduction in fat mass was significantly higher and the LBM/weight ratio significantly increased compared with the non-obese group. However, there was no significant change in lipid indices in the obese group. The TG level was significantly correlated with fat, especially with trunk fat. Gastrectomy resulted in improved lipid indices and a reduction in body weight, fat and LBM. The HDL-C significantly increased in the non-obese group for 1 year after gastrectomy and the reduction of TG level was positively correlated with fat

[Lipids and cerebrovascular disease - New therapeutic options in lowering LDL-cholesterol].

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Lovadi, Emese; Csécsei, Péter; Lovig, Csenge; Karádi, Zsófia; Szapáry, László

2016-12-01

Stroke is the third most common cause of death worldwide following myocardial infaction and malignancies, furthermore, its functional outcome is the worst of all conditions. Cholesterol, especially LDL-cholesterol plays a key role in the formation of atherosclerotic plaques. It has been verified recently that escalating incidence and mortality of cerebrovascular diseases are proportional to increased levels of LDL-cholesterol. Statin therapy undeniably reduces the risk of stroke, however other methods for decreasing lipid levels have not been proved significantly effective. Preventive effect of high-dose statin treatment is without doubt, although administration of such high dosage might require special precautions for patients with prior intracerebral hemorrhage and it also risks development of incident diabetes. The recently published IMPROVE-IT study is the first to prove that the addition of ezetimibe as a non-statin type drug, to statin treatment contributes to further reduction of LDL-cholesterol. The combination treatment results in additional decrease in the incidence and mortality of cerebrovascular events, without any expansion in the number or adverse effects. These results confirm the importance of any further reduction of LDL-cholesterol levels. Achieving target values with statin-ezetimibe combination allows administration of low to moderate dose of statin, which decreases risks of adverse effects related to high-dose statin therapy. Orv. Hetil., 2016, 157(52), 2059-2065.

Effectiveness of carthamus tinctorius L. in the restitution of lipid composition in irradiated rats

International Nuclear Information System (INIS)

Zahran, A.M.; Omran, M.F.; Mansour, S.Z.; Ibrahim, N.K.

2007-01-01

Lipid peroxidation is a well known example of oxidative damage in cell membranes, lipoproteins, and other lipid-containing structures. The degenerative process of lipid peroxidation is induced under conditions of oxidative stress. This study was designated to evaluate in one aspect, the susceptibility of blood and liver lipid fractions to oxidative stress under influence of whole body gamma irradiation (6.5 Gy). The other aspect was to investigate the compensatory role of the Safflower extract (Carthamus tinctorius L., Composite) a premier oil containing the highest levels of polyunsaturated fats (rich in n-6 PUFA) to maintain and restore the biological membranes from oxidative stress. Mixture of safflower essential oils and hydro-alcoholic extract was orally administered to Sprague Dawley rats by gavages vehicle (150 mg/ Kg body wt) for 21 successive days before exposure to y-rays and 7 days after irradiation. Exposure to y-rays resulted in significant increase in triacylglycerols, phospholipids, cholesterol indices and MDA contents. Meanwhile, the results show a significant decline in most fractionated unsaturated fatty acids concentrations. The administration of safflower essential oils and ethanolic extract exerted a noticeable compensation in the radiation-induced changes in most of the studied parameters. The results point out the promising role of safflower, a natural product, on oxidative damage and lipid composition

Genetic predisposition to increased blood cholesterol and triglyceride lipid levels and risk of Alzheimer disease: a Mendelian randomization analysis.

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Petroula Proitsi

2014-09-01

Full Text Available Although altered lipid metabolism has been extensively implicated in the pathogenesis of Alzheimer disease (AD through cell biological, epidemiological, and genetic studies, the molecular mechanisms linking cholesterol and AD pathology are still not well understood and contradictory results have been reported. We have used a Mendelian randomization approach to dissect the causal nature of the association between circulating lipid levels and late onset AD (LOAD and test the hypothesis that genetically raised lipid levels increase the risk of LOAD.We included 3,914 patients with LOAD, 1,675 older individuals without LOAD, and 4,989 individuals from the general population from six genome wide studies drawn from a white population (total n=10,578. We constructed weighted genotype risk scores (GRSs for four blood lipid phenotypes (high-density lipoprotein cholesterol [HDL-c], low-density lipoprotein cholesterol [LDL-c], triglycerides, and total cholesterol using well-established SNPs in 157 loci for blood lipids reported by Willer and colleagues (2013. Both full GRSs using all SNPs associated with each trait at p<5×10-8 and trait specific scores using SNPs associated exclusively with each trait at p<5 × 10-8 were developed. We used logistic regression to investigate whether the GRSs were associated with LOAD in each study and results were combined together by meta-analysis. We found no association between any of the full GRSs and LOAD (meta-analysis results: odds ratio [OR]=1.005, 95% CI 0.82-1.24, p = 0.962 per 1 unit increase in HDL-c; OR=0.901, 95% CI 0.65-1.25, p=0.530 per 1 unit increase in LDL-c; OR=1.104, 95% CI 0.89-1.37, p=0.362 per 1 unit increase in triglycerides; and OR=0.954, 95% CI 0.76-1.21, p=0.688 per 1 unit increase in total cholesterol. Results for the trait specific scores were similar; however, the trait specific scores explained much smaller phenotypic variance.Genetic predisposition to increased blood cholesterol and

Effect of vitamin E supplementation on serumic levels of lipids and lipoproteins in cholesterol-fed male rat

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M.H Khayat Nouri

2008-11-01

Full Text Available Hypercholesterolemia is one of the risk factors of cardiovascular diseases. High blood cholesterol affects the general health and increases the mortality rate of cardiovascular diseases. High levels of cholesterol in the diet increases LDL levels and decreases the activity of LDL receptors in the liver. Oxidation of vascular LDL lipoproteins increases the development of atherosclerosis. Previous studies have indicated that consumption of antioxidants decreases hypercholesterolemia. This study evaluates the effect of vitamin E supplementation on blood lipid levels in high cholesterol-fed rats. In this experimental study, three groups of male rats (n=10 for each group were used. The control group received basic diet and one of the other two groups received a diet containing one percent cholesterol and while the other received the same diet plus vitamin E supplement (2500 IU/kg in dry matter of the diet for one month. After determining the values of TC, LDL, VLDL, HDL and TG the results indicated that in rats fed with 1% cholesterol apart from HDL and VLDL the other lipids had increased significantly compared with the control group (p

High blood cholesterol levels

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Cholesterol - high; Lipid disorders; Hyperlipoproteinemia; Hyperlipidemia; Dyslipidemia; Hypercholesterolemia ... There are many types of cholesterol. The ones talked about most are: ... lipoprotein (HDL) cholesterol -- often called "good" cholesterol ...

Use of quantitative optical imaging to examine the role of cholesterol-rich lipid raft microdomains in the migration of breast cancer cells

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You, Minghai; Chen, Jianling; Wang, Shaobing; Dong, Shiqing; Wang, Yuhua; Xie, Shusen; Wang, Zhengchao; Yang, Hongqin

2018-04-01

Lipid rafts have been extensively studied and shown to be involved in many cancers, including breast cancer. However, the exact role of lipid rafts in the migration of breast cancer cells remains unclear. This study was designed to examine lipid rafts (cholesterol) in the plasma membrane of breast cancer cells (MDA-MB-231 and MCF-7) and normal breast epithelial cells (MCF-10A) through generalized polarization values, and further investigate the role of cholesterol-rich lipid rafts in the migration of breast cancer cells. The results showed that the plasma membrane in breast cancer cells was more orderly than that in normal epithelial cells; this was correlated with expression changes of matrix metallopeptidase 9 (MMP-9) and urokinase-type plasminogen activator receptor (uPAR), the markers of cancer cell migration. Moreover, the breast cancer cells were more sensitive to the reagent that induced cholesterol depletion than the normal breast epithelial cells, while the capacity of cancer cells to migrate decreased significantly according to changes in MMP-9 and uPAR expression. To our best knowledge, this is the first demonstration of the relationship between cholesterol-rich lipid rafts and the migration of breast cancer cells; it could be useful for the prevention of breast cancer and early treatment through reduction of the level of cholesterol in the plasma membrane of the cells.

Cholesterol tuning of BK ethanol response is enantioselective, and is a function of accompanying lipids.

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Chunbo Yuan

Full Text Available In the search to uncover ethanol's molecular mechanisms, the calcium and voltage activated, large conductance potassium channel (BK has emerged as an important molecule. We examine how cholesterol content in bilayers of 1,2-dioleoyl-3-phosphatidylethanolamine (DOPE/sphingomyelin (SPM and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylethanolamine (POPE/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylserine (POPS affect the function and ethanol sensitivity of BK. In addition, we examine how manipulation of cholesterol in biological membranes modulates ethanol's actions on BK. We report that cholesterol levels regulate the change in BK channel open probability elicited by 50 mM ethanol. Low levels of cholesterol (<20%, molar ratio supports ethanol activation, while high levels of cholesterol leads to ethanol inhibition of BK. To determine if cholesterol affects BK and its sensitivity to ethanol through a direct cholesterol-protein interaction or via an indirect action on the lipid bilayer, we used the synthetic enantiomer of cholesterol (ent-CHS. We found that 20% and 40% ent-CHS had little effect on the ethanol sensitivity of BK, when compared with the same concentration of nat-CHS. We accessed the effects of ent-CHS and nat-CHS on the molecular organization of DOPE/SPM monolayers at the air/water interface. The isotherm data showed that ent-CHS condensed DOPE/SPM monolayer equivalently to nat-CHS at a 20% concentration, but slightly less at a 40% concentration. Atomic force microscopy (AFM images of DOPE/SPM membranes in the presence of ent-CHS or nat-CHS prepared with LB technique or vesicle deposition showed no significant difference in topographies, supporting the interpretation that the differences in actions of nat-CHS and ent-CHS on BK channel are not likely from a generalized action on bilayers. We conclude that membrane cholesterol influences ethanol's modulation of BK in a complex manner, including an interaction with the channel protein

Influence of cholesterol and ceramide VI on the structure of multilamellar lipid membranes at water exchange

International Nuclear Information System (INIS)

Ryabova, N. Yu.; Kiselev, M. A.; Balagurov, A. M.

2010-01-01

The structural changes in the multilamellar lipid membranes of dipalmitoylphosphatidylcholine (DPPC)/cholesterol and DPPC/ceramide VI binary systems during hydration and dehydration have been studied by neutron diffraction. The effect of cholesterol and ceramide on the kinetics of water exchange in DPPC membranes is characterized. Compared to pure DPPC, membranes of binary systems swell faster during hydration (with a characteristic time of ∼30 min). Both compounds, ceramide VI and cholesterol, similarly affect the hydration of DPPC membranes, increasing the repeat distance due to the bilayer growth. However, in contrast to cholesterol, ceramide significantly reduces the thickness of the membrane water layer. The introduction of cholesterol into a DPPC membrane slows down the change in the parameters of the bilayer internal structure during dehydration. In the DPPC/ceramide VI/cholesterol ternary system (with a molar cholesterol concentration of 40%), cholesterol is partially released from the lamellar membrane structure into the crystalline phase.

Zonal differences in the distribution and morphology of lipid droplets using 4-amino-pyrazolo-(3,4 d) pyrimidine to lower cholesterol level in the rat adrenal.

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Szabó, D; Somogyi, J; Acs, Z; Mihály, K

1980-01-01

The effect of reduced blood and adrenal cholesterol levels on adrenocortical lipid droplets have been examined by treating adult rats with 4-amino-pyrazolo-(3,4 d) pyrimidine (4-APP), a drug that inhibits hepatic secretion of lipoproteins. Lowering the blood cholesterol level and the cholesterol content of the adrenals was associated with a marked reduction in the lipid droplets and with a simultaneous increase in their electron density in the inner cortical zones. In the zona glomerulosa cells, no perceptible differences were found in the quantity and morphology of lipid droplets. These data suggest that reduced blood and adrenal cholesterol levels do not affect lipids located in the zona glomerulosa and in the inner cortical zones in the same way, probably due to differences in their intracellular lipid dynamism. Noteworthy, that in spite of the marked lipid depletion, the adrenal glands retained their responsiveness to ACTH stimulation.

Phytosterol stearate esters elicit similar responses on plasma lipids and cholesterol absorption but different responses on fecal neutral sterol excretion and hepatic free cholesterol in male Syrian hamsters.

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Ash, Mark M; Hang, Jiliang; Dussault, Patrick H; Carr, Timothy P

2011-07-01

The dietary impact of specific phytosterols incorporated into phytosterol fatty acid esters has not been elucidated. Therefore, we tested the hypothesis that phytosterol esters containing different sterol moieties (sitosterol, sitostanol, or stigmasterol) but the same fatty acid moiety (stearic acid) produce different effects on cholesterol metabolism. Male Syrian hamsters were fed sitosterol, sitostanol, and stigmasterol stearate esters (25 g/kg diet) in an atherogenic diet containing cholesterol (1.2 g/kg) and coconut oil (80 g/kg). The phytosterol stearates produced no decrease in cholesterol absorption or plasma non-high-density lipoprotein cholesterol despite a reduction in liver free cholesterol in hamsters fed both sitosterol and sitostanol stearate diets. In addition, sitosterol stearate significantly increased fecal esterified and total neutral sterol excretion. Stigmasterol stearate did not differ from control in neutral sterol excretion, plasma lipids, or hepatic lipid concentration. Sitosterol stearate demonstrated the highest level of net intestinal hydrolysis, whereas sitostanol and stigmasterol stearate equivalently demonstrated the lowest. The cholesterol-lowering effect in liver-but not plasma-and the limited presence of fecal free sterols indicate that intact (unhydrolyzed) phytosterol stearates may impact cholesterol metabolism by mechanisms unrelated to the role of free phytosterols. The consumption of phytosterol esters at 2.5% of the diet elicited only modest impacts on cholesterol metabolism, although sitosterol stearate had a slightly greater therapeutic impact by lowering liver free cholesterol and increasing esterified and total neutral sterol fecal excretion, possibly due to a greater level of intestinal hydrolysis. Copyright © 2011 Elsevier Inc. All rights reserved.

PEG-lipid micelles enable cholesterol efflux in Niemann-Pick Type C1 disease-based lysosomal storage disorder

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Brown, Anna; Patel, Siddharth; Ward, Carl; Lorenz, Anna; Ortiz, Mauren; Duross, Allison; Wieghardt, Fabian; Esch, Amanda; Otten, Elsje G.; Heiser, Laura M.; Korolchuk, Viktor I.; Sun, Conroy; Sarkar, Sovan; Sahay, Gaurav

2016-08-01

2-Hydroxy-propyl-β-cyclodextrin (HPβCD), a cholesterol scavenger, is currently undergoing Phase 2b/3 clinical trial for treatment of Niemann Pick Type C-1 (NPC1), a fatal neurodegenerative disorder that stems from abnormal cholesterol accumulation in the endo/lysosomes. Unfortunately, the extremely high doses of HPβCD required to prevent progressive neurodegeneration exacerbates ototoxicity, pulmonary toxicity and autophagy-based cellular defects. We present unexpected evidence that a poly (ethylene glycol) (PEG)-lipid conjugate enables cholesterol clearance from endo/lysosomes of Npc1 mutant (Npc1-/-) cells. Herein, we show that distearyl-phosphatidylethanolamine-PEG (DSPE-PEG), which forms 12-nm micelles above the critical micelle concentration, accumulates heavily inside cholesterol-rich late endosomes in Npc1-/- cells. This potentially results in cholesterol solubilization and leakage from lysosomes. High-throughput screening revealed that DSPE-PEG, in combination with HPβCD, acts synergistically to efflux cholesterol without significantly aggravating autophagy defects. These well-known excipients can be used as admixtures to treat NPC1 disorder. Increasing PEG chain lengths from 350 Da-30 kDa in DSPE-PEG micelles, or increasing DSPE-PEG content in an array of liposomes packaged with HPβCD, improved cholesterol egress, while Pluronic block copolymers capable of micelle formation showed slight effects at high concentrations. We postulate that PEG-lipid based nanocarriers can serve as bioactive drug delivery systems for effective treatment of lysosomal storage disorders.

PEG-lipid micelles enable cholesterol efflux in Niemann-Pick Type C1 disease-based lysosomal storage disorder

Science.gov (United States)

Brown, Anna; Patel, Siddharth; Ward, Carl; Lorenz, Anna; Ortiz, Mauren; DuRoss, Allison; Wieghardt, Fabian; Esch, Amanda; Otten, Elsje G.; Heiser, Laura M.; Korolchuk, Viktor I.; Sun, Conroy; Sarkar, Sovan; Sahay, Gaurav

2016-01-01

2-Hydroxy-propyl-β-cyclodextrin (HPβCD), a cholesterol scavenger, is currently undergoing Phase 2b/3 clinical trial for treatment of Niemann Pick Type C-1 (NPC1), a fatal neurodegenerative disorder that stems from abnormal cholesterol accumulation in the endo/lysosomes. Unfortunately, the extremely high doses of HPβCD required to prevent progressive neurodegeneration exacerbates ototoxicity, pulmonary toxicity and autophagy-based cellular defects. We present unexpected evidence that a poly (ethylene glycol) (PEG)-lipid conjugate enables cholesterol clearance from endo/lysosomes of Npc1 mutant (Npc1−/−) cells. Herein, we show that distearyl-phosphatidylethanolamine-PEG (DSPE-PEG), which forms 12-nm micelles above the critical micelle concentration, accumulates heavily inside cholesterol-rich late endosomes in Npc1−/− cells. This potentially results in cholesterol solubilization and leakage from lysosomes. High-throughput screening revealed that DSPE-PEG, in combination with HPβCD, acts synergistically to efflux cholesterol without significantly aggravating autophagy defects. These well-known excipients can be used as admixtures to treat NPC1 disorder. Increasing PEG chain lengths from 350 Da-30 kDa in DSPE-PEG micelles, or increasing DSPE-PEG content in an array of liposomes packaged with HPβCD, improved cholesterol egress, while Pluronic block copolymers capable of micelle formation showed slight effects at high concentrations. We postulate that PEG-lipid based nanocarriers can serve as bioactive drug delivery systems for effective treatment of lysosomal storage disorders. PMID:27572704

Membrane cholesterol effect on the 5-HT2A receptor: Insights into the lipid-induced modulation of an antipsychotic drug target.

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Ramírez-Anguita, Juan Manuel; Rodríguez-Espigares, Ismael; Guixà-González, Ramon; Bruno, Agostino; Torrens-Fontanals, Mariona; Varela-Rial, Alejandro; Selent, Jana

2018-01-01

The serotonin 5-hydroxytryptamine 2A (5-HT 2A ) receptor is a G-protein-coupled receptor (GPCR) relevant for the treatment of CNS disorders. In this regard, neuronal membrane composition in the brain plays a crucial role in the modulation of the receptor functioning. Since cholesterol is an essential component of neuronal membranes, we have studied its effect on the 5-HT 2A receptor dynamics through all-atom MD simulations. We find that the presence of cholesterol in the membrane increases receptor conformational variability in most receptor segments. Importantly, detailed structural analysis indicates that conformational variability goes along with the destabilization of hydrogen bonding networks not only within the receptor but also between receptor and lipids. In addition to increased conformational variability, we also find receptor segments with reduced variability. Our analysis suggests that this increased stabilization is the result of stabilizing effects of tightly bound cholesterol molecules to the receptor surface. Our finding contributes to a better understanding of membrane-induced alterations of receptor dynamics and points to cholesterol-induced stabilizing and destabilizing effects on the conformational variability of GPCRs. © 2017 International Union of Biochemistry and Molecular Biology, Inc.

Promotive effect of Bofutsushosan (Fangfengtongshengsan) on lipid and cholesterol excretion in feces in mice treated with a high-fat diet.

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Akaki, Junji; Tachi, Shiori; Nakamura, Naoki; Arai, Tetsuya; Yamasaki, Hiroo; Inoue, Makoto; Makino, Toshiaki

2018-06-28

Bofutsushosan (fangfengtongshengsan in Chinese, BTS) is a formula in traditional Japanese Kampo medicine and Chinese medicine comprising 18 crude drugs that is used for treating obesity and metabolic syndrome. We evaluated the promotive effects of BTS on lipid and cholesterol elimination in mice. Mice were reared with a high-fat diet containing boiled water extract of BTS for 30 days, and their biochemical parameters as well as the weight and lipid content of feces were measured. We also measured cholesterol uptake into Caco-2 cells cultured with or without BTS extract. The body weight and amounts of visceral fat and subcutaneous fat on day 28; the weights of epididymal, perirenal, and mesenteric fat; and the serum concentrations of triglyceride, glucose, and hemoglobin A1c on day 30 were significantly lower in the BTS extract-treated groups than in the control in a dose-dependent manner. The amounts of lipid and cholesterol in the feces collected from day 6-23 were significantly greater than in the control. When Caco-2 cells were incubated with BTS extract, the uptake of cholesterol into cells was significantly reduced in a concentration-dependent manner. Among the components of BTS, the methanol extracts of Platycodi Radix and Zingiberis Rhizoma contribute but the extracts of Ephedrae Herba and Rhei Rhizoma counteract the suppressive effect of BTS on cholesterol uptake into Caco-2 cells. BTS has beneficial effects on obesity and metabolic syndrome, and its mechanisms of action include the promotion of lipid elimination and the inhibition of cholesterol absorption in the intestine. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Nitrogen-deprivation elevates lipid levels in Symbiodinium spp. by lipid droplet accumulation: morphological and compositional analyses.

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Pei-Luen Jiang

Full Text Available Stable cnidarian-dinoflagellate (genus Symbiodinium endosymbioses depend on the regulation of nutrient transport between Symbiodinium populations and their hosts. It has been previously shown that the host cytosol is a nitrogen-deficient environment for the intracellular Symbiodinium and may act to limit growth rates of symbionts during the symbiotic association. This study aimed to investigate the cell proliferation, as well as ultrastructural and lipid compositional changes, in free-living Symbiodinium spp. (clade B upon nitrogen (N-deprivation. The cell proliferation of the N-deprived cells decreased significantly. Furthermore, staining with a fluorescent probe, boron dipyrromethane 493/503 (BODIPY 493/503, indicated that lipid contents progressively accumulated in the N-deprived cells. Lipid analyses further showed that both triacylglycerol (TAG and cholesterol ester (CE were drastically enriched, with polyunsaturated fatty acids (PUFA; i.e., docosahexaenoic acid, heneicosapentaenoic acid, and oleic acid became more abundant. Ultrastructural examinations showed that the increase in concentration of these lipid species was due to the accumulation of lipid droplets (LDs, a cellular feature that have previously shown to be pivotal in the maintenance of intact endosymbioses. Integrity of these stable LDs was maintained via electronegative repulsion and steric hindrance possibly provided by their surface proteins. Proteomic analyses of these LDs identified proteins putatively involved in lipid metabolism, signaling, stress response and energy metabolism. These results suggest that LDs production may be an adaptive response that enables Symbiodinium to maintain sufficient cellular energy stores for survival under the N-deprived conditions in the host cytoplasm.

Lysosomal degradation of membrane lipids.

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Kolter, Thomas; Sandhoff, Konrad

2010-05-03

The constitutive degradation of membrane components takes place in the acidic compartments of a cell, the endosomes and lysosomes. Sites of lipid degradation are intralysosomal membranes that are formed in endosomes, where the lipid composition is adjusted for degradation. Cholesterol is sorted out of the inner membranes, their content in bis(monoacylglycero)phosphate increases, and, most likely, sphingomyelin is degraded to ceramide. Together with endosomal and lysosomal lipid-binding proteins, the Niemann-Pick disease, type C2-protein, the GM2-activator, and the saposins sap-A, -B, -C, and -D, a suitable membrane lipid composition is required for degradation of complex lipids by hydrolytic enzymes. Copyright 2009 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Home-Use Tests - Cholesterol

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... Medical Procedures In Vitro Diagnostics Home Use Tests Cholesterol Share Tweet Linkedin Pin it More sharing options ... a home-use test kit to measure total cholesterol. What cholesterol is: Cholesterol is a fat (lipid) ...

Cholesterol and fatty acid composition of longissimus thoracis from water buffalo (Bubalus bubalis) and Brahman-influenced cattle raised under savannah conditions.

Science.gov (United States)

Giuffrida-Mendoza, Maria; Arenas de Moreno, Lilia; Huerta-Leidenz, Nelson; Uzcátegui-Bracho, Sojan; Valero-Leal, Kutchynskaya; Romero, Sonia; Rodas-González, Argenis

2015-08-01

Male (n=66) water buffalo (Buffalo) and Brahman-influenced cattle (Brahman) were born, raised, weaned, fattened on grazing savannah and harvested at two different ages (19 and 24months) to compare lipid composition of the longissimus thoracis muscle. Half of the animals were castrated at seven months of age (MOA) to examine the castration effects. At 24 MOA Brahman steers showed the highest content of total lipids (P<0.05). No significant variation was detected in cholesterol content for either the main or interaction effects in the age groups. Some individual fatty acids varied with the species (P<0.05), however, interspecific similarities were found in fatty acid ratios. For health-related indices, only atherogenic index (AI) showed lower values in favor of Buffalo meat (P<0.05) at both harvesting ages. Although, meat derived from both bovid groups was leaner and showed lower cholesterol level, AI indicates that Buffalo meat might be beneficial from a human health standpoint. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of supplemental copper on the serum lipid profile, meat quality, and carcass composition of goat kids.

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Huang, Yanling; Wang, Yong; Lin, Xi; Guo, Chunhua

2014-06-01

To evaluate the effects of copper (Cu) supplementation on the serum lipid profile, meat quality, and carcass composition of goat kids, thirty-five 3-4-month-old Jian Yang big-eared goat kids (BW 20.3±0.6 kg) were randomly assigned to one of seven dietary Cu treatments (n=5/treatment). The dietary Cu concentrations were: (1) control (no supplemental Cu), (2) 20 mg, (3) 40 mg, (4) 80 mg, (5) 160 mg, (6) 320 mg, and (7) 640 mg of supplemental Cu/kg dry matter (DM). Copper was supplemented as CuSO4.5H2O (25.2 % Cu). The goats were fed a high-concentrate basal diet with the different concentrations of supplemental Cu/kg DM for 96 days. The serum lipid profile was determined on day 51 and day 96. Meat quality and carcass composition of longissimus dorsi muscle were measured after the goats were slaughtered at 96 days. Serum total cholesterol, triglycerides, high density lipoprotein-cholesterol (HDL-C), and low density lipoprotein-cholesterol (LDL-C) were not affected by treatment (P>0.18). No differences were observed in drip loss, cooking loss, a* (redness/greenness) and b* (yellowness/blueness) values (P>0.17); however, the 24-h pH value (linear; P=0.0009) and L* (brightness) value (linear; P=0.0128) decreased, and shear force increased (linear; P=0.0005) as Cu supplementation increased. The intramuscular fat (%) increased (linear; P=0.001) as supplemental Cu increased. No differences (P>0.21) in the moisture, crude protein, and ash (%) were observed. Results of this study indicate that supplemental Cu does not modify the serum lipid profile; however, it can impact intramuscular fat content and the meat quality of goat kids.

Lipid Composition Of Two Marine Fishes – Scomber scombrus And ...

African Journals Online (AJOL)

Lipids from two species of marine fish – Scomber scombrus and Trachurus trachurus were investigated. Fish oil from Trachurus trachurus had higher oil yield than that of Scomber scombrus. The lipids contain high levels of triacylglycerol 228 – 250 mg%, cholesterol 160 – 235 mg%, and phospholipids 2.2 – 2.4 mg%.

Concanavalin A-binding cholesterol crystallization inhibiting and promoting activity in bile from patients with Crohn's disease compared to patients with ulcerative colitis.

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Keulemans, Y C; Mok, K S; Slors, J F; Brink, M A; Gouma, D J; Tytgat, G N; Groen, A K

1999-10-01

Crohn's disease is a risk factor for gallstone formation. In contrast, patients with ulcerative colitis have an incidence of gallstone formation comparable to the general population. The reason for this difference is not known. The aim of this study was to elucidate the factors controlling cholesterol crystallization in gallbladder bile of Crohn's disease and ulcerative colitis patients. Gallbladder bile was obtained by aspiration during bowel resections (26 Crohn's disease patients, 20 ulcerative colitis patients). Biliary lipid composition, crystal detection time and the effect of extraction of the concanavalin A-binding fraction on crystal formation were determined. Cholesterol crystals were present in seven of the 26 bile samples of Crohn's disease-patients and one of the 20 ulcerative colitis patients. Four of the bile samples of Crohn's disease patients were fast nucleating. None of the 20 ulcerative colitis patients had fast nucleating bile. Lipid composition, total lipid concentration and CSI were not significantly different between the two groups. In Crohn's disease patients extraction of concanavalin A-binding fraction decreased crystallization in 10 bile samples but accelerated crystallization in one bile sample. In eight bile samples from ulcerative colitis patients crystallization increased after concanavalin A-binding fraction extraction. Compared to ulcerative colitis patients, gallbladder bile of Crohn's disease patients showed increased cholesterol crystallization despite comparable lipid composition and cholesterol saturation index. This difference is caused by increased cholesterol crystallization-promoting activity. Bile from ulcerative colitis patients contains a Con A-binding factor which inhibits cholesterol crystallization.

Effect of a high-fat-high-cholesterol diet on gallbladder bile acid composition and gallbladder motility in dogs.

Science.gov (United States)

Kakimoto, Toshiaki; Kanemoto, Hideyuki; Fukushima, Kenjiro; Ohno, Koichi; Tsujimoto, Hajime

2017-12-01

OBJCTIVE To investigate the effects of dietary lipid overload on bile acid metabolism and gallbladder motility in healthy dogs. ANIMALS 7 healthy Beagles. PROCEDURES In a crossover study, dogs were fed a high-fat-high-cholesterol diet (HFCD) or a low-fat diet (LFD) for a period of 2 weeks. After a 4-month washout period, dogs were fed the other diet for 2 weeks. Before and at the end of each feeding period, the concentrations of each of the gallbladder bile acids, cholecystokinin (CCK)-induced gallbladder motility, and bile acid metabolism-related hepatic gene expression were examined in all dogs. RESULTS The HFCD significantly increased plasma total cholesterol concentrations. The HFCD also increased the concentration of taurochenodeoxycholic acid and decreased the concentration of taurocholic acid in bile and reduced gallbladder contractility, whereas the LFD significantly decreased the concentration of taurodeoxycholic acid in bile. Gene expression analysis revealed significant elevation of cholesterol 7α-hydroxylase mRNA expression after feeding the HFCD for 2 weeks, but the expression of other genes was unchanged. CONCLUSIONS AND CLINICAL RELEVANCE Feeding the HFCD and LFD for 2 weeks induced changes in gallbladder bile acid composition and gallbladder motility in dogs. In particular, feeding the HFCD caused an increase in plasma total cholesterol concentration, an increase of hydrophobic bile acid concentration in bile, and a decrease in gallbladder sensitivity to CCK. These results suggested that similar bile acid compositional changes and gallbladder hypomotility might be evident in dogs with hyperlipidemia.

Mitochondrial GWA Analysis of Lipid Profile Identifies Genetic Variants to Be Associated with HDL Cholesterol and Triglyceride Levels.

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Antònia Flaquer

Full Text Available It has been suggested that mitochondrial dysfunction has an influence on lipid metabolism. The fact that mitochondrial defects can be accumulated over time as a normal part of aging may explain why cholesterol levels often are altered with age. To test the hypothesis whether mitochondrial variants are associated with lipid profile (total cholesterol, LDL, HDL, and triglycerides we analyzed a total number of 978 mitochondrial single nucleotide polymorphisms (mtSNPs in a sample of 2,815 individuals participating in the population-based KORA F4 study. To assess mtSNP association while taking the presence of heteroplasmy into account we used the raw signal intensity values measured on the microarray and applied linear regression. Ten mtSNPs (mt3285, mt3336, mt5285, mt6591, mt6671, mt9163, mt13855, mt13958, mt14000, and mt14580 were significantly associated with HDL cholesterol and one mtSNP (mt15074 with triglycerides levels. These results highlight the importance of the mitochondrial genome among the factors that contribute to the regulation of lipid levels. Focusing on mitochondrial variants may lead to further insights regarding the underlying physiological mechanisms, or even to the development of innovative treatments. Since this is the first mitochondrial genome-wide association analysis (mtGWAS for lipid profile, further analyses are needed to follow up on the present findings.

EFFECT OF DIETARY OLIVE OIL/CHOLESTEROL ON SERUM LIPOPROTEINS, LIPID PEROXIDATION, AND ATHEROSCLEROSIS IN RABBITS

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R MAHDAVI

2003-03-01

Full Text Available Introduction: High plasma cholesterol levels, mainly LDL are a widely recognized major risk factor for Coronary Heart Disease (CHD. According to the epidemiologic studies findings, people from the Mediterranean countries, have lower CHD rats than other countries, in these countries usual diet is high in olive oil. The present study compares the effects of cholesterol enriched diet with or without adding olive oil on serum Lipoproteins, lipid per oxidation, and atherosclerosis development. Method: Twenty Dutch male rabbits were Categorized to four groups (one group as Control, and others as Experimental. They received one of standard, cholesterol - rich, olive oil rich and combined (cholesterol + olive oil diet for Twelve weeks. Fasting blood samples from heart were collected at the beginning, and the end of Experimental period. Means of total cholesterol, HDL-Ctriglycerides, MDA and antioxidant caperimental period, significant differences were showed in total cholesterol, HDL-C, triglyceride and MDA between groups. Results: The comparison of cholesterol rich diet with cholesterol + olive oil showed a higher mean of MDA in cholesterol rich group (P < 0.001. Biochemical factors and aortic lesion degree showed no significant difference between standard and olive oil group. Aortic lesions in cholesterol + olive oil showed nonsignificant lower degree than cholesterol group. Discussion: This findings showed preventive effect of olive oil against atherosclerosis which is independent of plasma lipoprotein effect, and suggested that probably olive oil acts on arteries directly.

Octopus lipid and vitamin E composition: interspecies, interorigin, and nutritional variability.

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Torrinha, Alvaro; Cruz, Rebeca; Gomes, Filipa; Mendes, Eulália; Casal, Susana; Morais, Simone

2014-08-20

Octopus vulgaris, Octopus maya, and Eledone cirrhosa from distinct marine environments [Northeast Atlantic (NEA), Northwest Atlantic (NWA), Eastern Central Atlantic, Western Central Atlantic (WCA), Pacific Ocean, and Mediterranean Sea] were characterized regarding their lipid and vitamin E composition. These species are those commercially more relevant worldwide. Significant interspecies and interorigin differences were observed. Unsaturated fatty acids account for more than 65% of total fatty acids, mostly ω-3 PUFA due to docosahexaenoic (18.4-29.3%) and eicosapentanoic acid (11.4-23.9%) contributions. The highest ω-3 PUFA amounts and ω-3/ω-6 ratios were quantified in the heaviest specimens, O. vulgaris from NWA, with high market price, and simultaneously in the lowest graded samples, E. cirrhosa from NEA, of reduced dimensions. Although having the highest cholesterol contents, E. cirrhosa from NEA and O. maya from WCA have also higher protective fatty acid indexes. Chemometric discrimination allowed clustering the selected species and several origins based on lipid and vitamin E profiles.

Part II: Effects of gamma irradiation on lipid and cholesterol oxidation in mechanically deboned turkey meat

International Nuclear Information System (INIS)

Farkas, J.; Andrassy, E.; Meszaros, L.; Beczner, J.; Polyak-Feher, K.; Gaal, O.; Lebovics, V.K.; Lugasi, A.

2009-01-01

The pasteurizing effect of a 2 kGy radiation dose on non-frozen mechanically deboned turkey meat was achieved without increase in cholesterol oxidation products or increases in thiobarbituric acid reactive substance values during 15 d of chilled storage following the treatments, while untreated samples were spoiled. The addition of antioxidants, such as thyme oil or α-tocopherol plus ascorbic acid, significantly inhibited the oxidative changes of cholesterol and lipids during 3 kGy treatment. (author)

Effect of Flaxseed Meals and Extracts on Lipid Stability in a Stored Meat Product.

Science.gov (United States)

Waszkowiak, Katarzyna; Rudzińska, Magdalena

2014-01-01

Flaxseeds have been recently in focus due to the antioxidant capacity of some of their compounds. However, there is a lack of easily accessible information concerning their activity against lipid oxidation in food systems. Therefore, the aim of the study was to determine the effect of defatted meals (DFM) and the aqueous extracts (AFE) obtained from brown and golden flaxseeds on lipid oxidation in pork meatballs. Fatty acid composition, peroxide value (PV), thiobarbituric acid reactive substances (TBARS) and cholesterol content were monitored during 6 months of freezer storage. Cholesterol oxidation products were identified and quantified. Both DFM and AFE limited fatty acid and cholesterol oxidation during meatball storage. Their antioxidant effect depended on flax variety (brown or golden) and preparation type (DFM or AFE). Lower level of PV and TBARS, compared with the ones with AFE, were noted in meatballs with DFM. Both DFM and AFE, from the brown seed variety, protect the lipids against oxidation to a higher extent. During the storage, a cholesterol degradation was observed. AFE (particularly from the brown variety) limited changes in cholesterol content. Moreover, they stabilized fatty acid composition of stored meatballs. However, DFM efficiently inhibited cholesterol oxidation.

INFLUENCE OF BIOPREPARATIONS FROM DRY SOYBEAN AND SUNFLOWER LECITHINS ON SERUM LIPIDS COMPOSITION

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H. V. Dziak

2014-04-01

Full Text Available Dry lecithin, which is a mixture of polar phospholipids, neutral lipids, free fatty acids, glycolipids, carbohydrates, and small amounts of moisture, is a promising object for biologic-hepatoprotectors creation. One of its pharmacological activity displays is its influence on serum lipids, in particular transport forms of these lipids. The influence of dry soy lecithin and sunflower on hyperlipoproteinemia ratio and other lipid disorders is studied. It is shown that low-fat dry soybean lecithin showed hypocholesterolemic activity against all studied forms of serum cholesterol. Nonfat dry sunflower lecithin had similar but somewhat less prominent effect. However reduced concentration of high density lipoprotein cholesterol under sunflower lecithin developed right before soya lecithin. Both lecithin prevented the development of dyslipidemia induced carbon tetrachloride.

Improvement of Lipid Profile Is Accompanied by Atheroprotective Alterations in High-Density Lipoprotein Composition Upon Tumor Necrosis Factor Blockade A Prospective Cohort Study in Ankylosing Spondylitis

NARCIS (Netherlands)

Eijk, van I.C.; Vries, de M.K.; Levels, J.H.M.; Peters, M.J.L.; Huizer, E.E.; Dijkmans, B.A.C.; Horst - Bruinsma, van der I.E.; Hazenberg, B.P.C.; Stadt, van de R.J.; Wolbink, G.; Nurmohamed, M.T.

2009-01-01

Objective. Cardiovascular mortality is increased in ankylosing spondylitis (AS), and inflammation plays an important role. Inflammation deteriorates the lipid profile and alters high-density lipoprotein cholesterol (HDL-c) composition, reflected by increased concentrations of serum amyloid A (SAA)

The effects of amoxicillin and vancomycin on parameters reflecting cholesterol metabolism.

Science.gov (United States)

Baumgartner, S; Reijnders, D; Konings, M C J M; Groen, A K; Lütjohann, D; Goossens, G H; Blaak, E E; Plat, J

2017-10-01

Changes in the microbiota composition have been implicated in the development of obesity and type 2 diabetes. However, not much is known on the involvement of gut microbiota in lipid and cholesterol metabolism. In addition, the gut microbiota might also be a potential source of plasma oxyphytosterol and oxycholesterol concentrations (oxidation products of plant sterols and cholesterol). Therefore, the aim of this study was to modulate the gut microbiota by antibiotic therapy to investigate effects on parameters reflecting cholesterol metabolism and oxyphytosterol concentrations. A randomized, double blind, placebo-controlled trial was performed in which 55 obese, pre-diabetic men received oral amoxicillin (broad-spectrum antibiotic), vancomycin (antibiotic directed against Gram-positive bacteria) or placebo (microcrystalline cellulose) capsules for 7days (1500mg/day). Plasma lipid and lipoprotein, non-cholesterol sterol, bile acid and oxy(phyto)sterol concentrations were determined at baseline and after 1-week intervention. Plasma secondary bile acids correlated negatively with cholestanol (marker for cholesterol absorption, r=-0.367; Pcholesterol synthesis, r=0.430; Pcholesterol metabolism, plasma TAG, total cholesterol, LDL-C or HDL-C concentrations as compared to placebo. In addition, both antibiotic treatments did not affect individual isoforms or total plasma oxyphytosterol or oxycholesterol concentrations. Despite strong correlations between plasma bile acid concentrations and cholesterol metabolism (synthesis and absorption), amoxicillin and vancomycin treatment for 7days did not affect plasma lipid and lipoprotein, plasma non-cholesterol sterol and oxy(phyto)sterol concentrations in obese, pre-diabetic men. Copyright © 2017 Elsevier B.V. All rights reserved.

Human Immunodeficiency Virus Type 1 Nef protein modulates the lipid composition of virions and host cell membrane microdomains

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Geyer Matthias

2007-10-01

Full Text Available Abstract Background The Nef protein of Human Immunodeficiency Viruses optimizes viral spread in the infected host by manipulating cellular transport and signal transduction machineries. Nef also boosts the infectivity of HIV particles by an unknown mechanism. Recent studies suggested a correlation between the association of Nef with lipid raft microdomains and its positive effects on virion infectivity. Furthermore, the lipidome analysis of HIV-1 particles revealed a marked enrichment of classical raft lipids and thus identified HIV-1 virions as an example for naturally occurring membrane microdomains. Since Nef modulates the protein composition and function of membrane microdomains we tested here if Nef also has the propensity to alter microdomain lipid composition. Results Quantitative mass spectrometric lipidome analysis of highly purified HIV-1 particles revealed that the presence of Nef during virus production from T lymphocytes enforced their raft character via a significant reduction of polyunsaturated phosphatidylcholine species and a specific enrichment of sphingomyelin. In contrast, Nef did not significantly affect virion levels of phosphoglycerolipids or cholesterol. The observed alterations in virion lipid composition were insufficient to mediate Nef's effect on particle infectivity and Nef augmented virion infectivity independently of whether virus entry was targeted to or excluded from membrane microdomains. However, altered lipid compositions similar to those observed in virions were also detected in detergent-resistant membrane preparations of virus producing cells. Conclusion Nef alters not only the proteome but also the lipid composition of host cell microdomains. This novel activity represents a previously unrecognized mechanism by which Nef could manipulate HIV-1 target cells to facilitate virus propagation in vivo.

Formation of 3D cholesterol crystals from 2D nucleation sites in lipid bilayer membranes: implications for atherosclerosis.

Science.gov (United States)

Varsano, Neta; Fargion, Iael; Wolf, Sharon G; Leiserowitz, Leslie; Addadi, Lia

2015-02-04

Atherosclerosis is the major precursor of cardiovascular disease. The formation of cholesterol crystals in atherosclerotic plaques is associated with the onset of acute pathology. The cholesterol crystals induce physical injury in the plaque core, promoting cell apoptosis and triggering an increased inflammatory response. Herein we address the question of how cholesterol crystal formation occurs in atherosclerosis. We demonstrate that three-dimensional (3D) cholesterol crystals can undergo directed nucleation from bilayer membranes containing two-dimensional (2D) cholesterol crystalline domains. We studied crystal formation on supported lipid bilayers loaded with exogenous cholesterol and labeled using a monoclonal antibody that specifically recognizes ordered cholesterol arrays. Our findings show that 3D crystals are formed exclusively on the bilayer regions where there are segregated 2D cholesterol crystalline domains and that they form on the domains. This study has potentially significant implications for our understanding of the crucial step in the mechanism by which atherosclerotic lesions form.

Simulations of simple Bovine and Homo sapiens outer cortex ocular lens membrane models with a majority concentration of cholesterol.

Science.gov (United States)

Adams, Mark; Wang, Eric; Zhuang, Xiaohong; Klauda, Jeffery B

2017-11-21

The lipid composition of bovine and human ocular lens membranes has been probed, and a variety of lipids have been found including phosphatidylcholine (PC), phosphatidylethanolamine (PE), sphingomyelin (SM), and cholesterol (CHOL) with cholesterol being present in particularly high concentrations. In this study, we use the all-atom CHARMM36 force field to simulate binary, ternary, and quaternary mixtures as models of the ocular lens. High concentration of cholesterol, in combination with different and varying diversity of phospholipids (PL) and sphingolipids (SL), affect the structure of the ocular lens lipid bilayer. The following analyses were done for each simulation: surface area per lipid, component surface area per lipid, deuterium order parameters (S CD ), electron density profiles (EDP), membrane thickness, hydrogen bonding, radial distribution functions, clustering, and sterol tilt angle distribution. The S CD show significant bilayer alignment and packing in cholesterol-rich bilayers. The EDP show the transition from liquid crystalline to liquid ordered with the addition of cholesterol. Hydrogen bonds in our systems show the tendency for intramolecular interactions between cholesterol and fully saturated lipid tails for less complex bilayers. But with an increased number of components in the bilayer, the acyl chain of the lipids becomes a less important characteristic, and the headgroup of the lipid becomes more significant. Overall, cholesterol is the driving force of membrane structure of the ocular lens membrane where interactions between cholesterol, PL, and SL determine structure and function of the biomembrane. The goal of this work is to develop a baseline for further study of more physiologically realistic ocular lens lipid membranes. This article is part of a Special Issue entitled: Emergence of Complex Behavior in Biomembranes edited by Marjorie Longo. Copyright © 2017 Elsevier B.V. All rights reserved.

[Beclobrate (Turec) in the treatment of primary hyperlipoproteinemia. I. Effect on cholesterol, lipid and apoprotein levels].

Science.gov (United States)

Sznajd, J; Idzior-Waluś, B; Zabiński, J; Wybrańska, I; Korzus, G; Iwanejko, J

1990-01-01

The effects of a new fibric acid derivative--beclobrate (Turec, Zyma) on serum lipid and apoprotein concentrations in 63 patients with primary hyperlipoproteinemia were examined. Beclobrate was given in the evening, 100 mg, once daily. After 3 months of beclobrate treatment mean total cholesterol concentration in serum decreased from 9.35 to 7.73 mmol/l (17.3%), mean LDL-cholesterol concentration from 6.32 to 5.38 mmol/l (14.9%), mean HDL-cholesterol concentration increased by 0.21 mmol/l (15.3% of initial value). The greatest decrease was observed in triglyceride concentration--by 50% of the initial value. Apoprotein B concentration decreased by 19.7%, apoprotein A1 and A2 concentration increased by 20.3% and 26.8% respectively. Higher initial values of total cholesterol and triglyceride concentration in serum were associated with greater concentration decrease after beclobrate treatment.

Fermentation of soy milk via Lactobacillus plantarum improves dysregulated lipid metabolism in rats on a high cholesterol diet.

Directory of Open Access Journals (Sweden)

Yunhye Kim

Full Text Available We aimed to investigate whether in vitro fermentation of soy with L. plantarum could promote its beneficial effects on lipids at the molecular and physiological levels. Rats were fed an AIN76A diet containing 50% sucrose (w/w (CTRL, a modified AIN76A diet supplemented with 1% (w/w cholesterol (CHOL, or a CHOL diet where 20% casein was replaced with soy milk (SOY or fermented soy milk (FSOY. Dietary isoflavone profiles, serum lipids, hepatic and fecal cholesterol, and tissue gene expression were examined. The FSOY diet had more aglycones than did the SOY diet. Both the SOY and FSOY groups had lower hepatic cholesterol and serum triglyceride (TG than did the CHOL group. Only FSOY reduced hepatic TG and serum free fatty acids and increased serum HDL-CHOL and fecal cholesterol. Compared to CHOL, FSOY lowered levels of the nuclear forms of SREBP-1c and SREBP-2 and expression of their target genes, including FAS, SCD1, LDLR, and HMGCR. On the other hand, FSOY elevated adipose expression levels of genes involved in TG-rich lipoprotein uptake (ApoE, VLDLR, and Lrp1, fatty acid oxidation (PPARα, CPT1α, LCAD, CYP4A1, UCP2, and UCP3, HDL-biogenesis (ABCA1, ApoA1, and LXRα, and adiponectin signaling (AdipoQ, AdipoR1, and AdipoR2, as well as levels of phosphorylated AMPK and ACC. SOY conferred a similar expression profile in both liver and adipose tissues but failed to reach statistical significance in many of the genes tested, unlike FSOY. Our data indicate that fermentation may be a way to enhance the beneficial effects of soy on lipid metabolism, in part via promoting a reduction of SREBP-dependent cholesterol and TG synthesis in the liver, and enhancing adiponectin signaling and PPARα-induced expression of genes involved in TG-rich lipoprotein clearance, fatty acid oxidation, and reverse cholesterol transport in adipose tissues.

Communication: Orientational self-ordering of spin-labeled cholesterol analogs in lipid bilayers in diluted conditions

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Kardash, Maria E.; Dzuba, Sergei A., E-mail: dzuba@kinetics.nsc.ru [Voevodsky Institute of Chemical Kinetics and Combustion, 630090 Novosibirsk, Russia, and Novosibirsk State University, 630090 Novosibirsk (Russian Federation)

2014-12-07

Lipid-cholesterol interactions are responsible for different properties of biological membranes including those determining formation in the membrane of spatial inhomogeneities (lipid rafts). To get new information on these interactions, electron spin echo (ESE) spectroscopy, which is a pulsed version of electron paramagnetic resonance (EPR), was applied to study 3β-doxyl-5α-cholestane (DCh), a spin-labeled analog of cholesterol, in phospholipid bilayer consisted of equimolecular mixture of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and 1,2-dioleoyl-sn-glycero-3-phosphocholine. DCh concentration in the bilayer was between 0.1 mol.% and 4 mol.%. For comparison, a reference system containing a spin-labeled 5-doxyl-stearic acid (5-DSA) instead of DCh was studied as well. The effects of “instantaneous diffusion” in ESE decay and in echo-detected (ED) EPR spectra were explored for both systems. The reference system showed good agreement with the theoretical prediction for the model of spin labels of randomly distributed orientations, but the DCh system demonstrated remarkably smaller effects. The results were explained by assuming that neighboring DCh molecules are oriented in a correlative way. However, this correlation does not imply the formation of clusters of cholesterol molecules, because conventional continuous wave EPR spectra did not show the typical broadening due to aggregation of spin labels and the observed ESE decay was not faster than in the reference system. So the obtained data evidence that cholesterol molecules at low concentrations in biological membranes can interact via large distances of several nanometers which results in their orientational self-ordering.

Effects of Persian leek (Allium ampeloprasum) on hepatic lipids and the expression of proinflammatory gene in hamsters fed a high-fat/ high-cholesterol diet.

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Fatoorechi, Vahideh; Rismanchi, Marjan; Nasrollahzadeh, Javad

2016-01-01

Persian leek is one of the most widely used herbal foods among Iranians. In this study, effects of oral administration of Persian leek on plasma and liver lipids were examined in hamster. Male Syrian hamsters were randomly divided into three groups: control (standard diet), high fat control (high-fat/high-cholesterol diet), Persian leek (high-fat/high-cholesterol diet + 1% per weight of diet from dried powdered Persian leek) for 14 weeks. High fat diet increased plasma and liver lipids as compared to standard diet. Adding Persian leek to the high-fat/high-cholesterol diet resulted in no significant changes in the concentration of the plasma lipids or liver cholesterol. However, liver triglycerides (TG), plasma Alanine aminotransferase and gene expression of tumor necrosis factor- α were decreased in hamsters fed high-fat diet containing Persian leek as compared to high-fat diet only. Persian leek might be considered as a herbal food that can reduce liver TG accumulation induced by high fat diets.

Cholesterol-Induced Buckling in Physisorbed Polymer-Tethered Lipid Monolayers

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Christoph A. Naumann

2013-04-01

Full Text Available The influence of cholesterol concentration on the formation of buckling structures is studied in a physisorbed polymer-tethered lipid monolayer system using epifluorescence microscopy (EPI and atomic force microscopy (AFM. The monolayer system, built using the Langmuir-Blodgett (LB technique, consists of 3 mol % poly(ethylene glycol (PEG lipopolymers and various concentrations of the phospholipid, 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine (SOPC, and cholesterol (CHOL. In the absence of CHOL, AFM micrographs show only occasional buckling structures, which is caused by the presence of the lipopolymers in the monolayer. In contrast, a gradual increase of CHOL concentration in the range of 0–40 mol % leads to fascinating film stress relaxation phenomena in the form of enhanced membrane buckling. Buckling structures are moderately deficient in CHOL, but do not cause any notable phospholipid-lipopolymer phase separation. Our experiments demonstrate that membrane buckling in physisorbed polymer-tethered membranes can be controlled through CHOL-mediated adjustment of membrane elastic properties. They further show that CHOL may have a notable impact on molecular confinement in the presence of crowding agents, such as lipopolymers. Our results are significant, because they offer an intriguing prospective on the role of CHOL on the material properties in complex membrane architecture.

Low-carbohydrate diets reduce lipid accumulation and arterial inflammation in guinea pigs fed a high-cholesterol diet.

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Leite, Jose O; DeOgburn, Ryan; Ratliff, Joseph; Su, Randy; Smyth, Joan A; Volek, Jeff S; McGrane, Mary M; Dardik, Alan; Fernandez, Maria Luz

2010-04-01

Low-carbohydrate diets (LCD) efficiently induce weight loss and favorably affect plasma lipids, however, the effect of LCD on atherosclerosis is still argued. To evaluate the effect of LCD on the prevention of atherosclerosis. Twenty guinea pigs were fed either a LCD or a low-fat diet (LFD) in combination with high-cholesterol (0.25g/100g) for 12 weeks. The percentage energy of macronutrient distribution was 10:65:25 for carbohydrate:fat:protein for the LCD, and 55:20:25 for the LFD. Plasma lipids were measured using colorimetric assays. Plasma and aortic oxidized (oxLDL) were quantified using ELISA methods. Inflammatory cytokines were measured in aortic homogenates using an immunoassay. H&E stained sections of aortic sinus and Schultz stained sections of carotid arteries were examined. LDL cholesterol was lower in the LCD compared to the LFD group (71.9+/-34.8 vs. 81.7+/-26.9mg/dL; p=0.039). Aortic cholesterol was also lower in the LCD (4.98+/-1.3mg/g) compared to the LFD group (6.68+/-2.0mg/g); p<0.05. The Schultz staining method confirmed less aortic cholesterol accumulation in the LCD group. Plasma oxLDL did not differ between groups, however, aortic oxLDL was 61% lower in the LCD compared to the LFD group (p=0.045). There was a positive correlation (r=0.63, p=0.03) between oxLDL and cholesterol concentration in the aorta of LFD group, which was not observed in LCD group (r=-0.05, p=0.96). Inflammatory markers were reduced in guinea pigs from the LCD group (p<0.05) and they were correlated with the decreases in oxLDL in aorta. These results suggest that LCD not only decreases lipid deposition, but also prevents the accumulation of oxLDL and reduces inflammatory cytokines within the arterial wall and may prevent atherosclerosis. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Intercalation of small hydrophobic molecules in lipid bilayers containing cholesterol

Energy Technology Data Exchange (ETDEWEB)

Worcester, D.L.; Hamacher, K.; Kaiser, H.; Kulasekere, R.; Torbet, J. [Univ. of Missouri, Columbia, MO (United States)

1994-12-31

Partitioning of small hydrophobic molecules into lipid bilayers containing cholesterol has been studied using the 2XC diffractometer at the University of Missouri Research Reactor. Locations of the compounds were determined by Fourier difference methods with data from both deuterated and undeuterated compounds introduced into the bilayers from the vapor phase. Data fitting procedures were developed for determining how well the compounds were localized. The compounds were found to be localized in a narrow region at the center of the hydrophobic layer, between the two halves of the bilayer. The structures are therefore intercalated structures with the long axis of the molecules in the plane of the bilayer.

Intercalation of small hydrophobic molecules in lipid bilayers containing cholesterol

International Nuclear Information System (INIS)

Worcester, D.L.; Hamacher, K.; Kaiser, H.; Kulasekere, R.; Torbet, J.

1994-01-01

Partitioning of small hydrophobic molecules into lipid bilayers containing cholesterol has been studied using the 2XC diffractometer at the University of Missouri Research Reactor. Locations of the compounds were determined by Fourier difference methods with data from both deuterated and undeuterated compounds introduced into the bilayers from the vapor phase. Data fitting procedures were developed for determining how well the compounds were localized. The compounds were found to be localized in a narrow region at the center of the hydrophobic layer, between the two halves of the bilayer. The structures are therefore intercalated structures with the long axis of the molecules in the plane of the bilayer

Cholesterol asymmetry in synaptic plasma membranes.

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Wood, W Gibson; Igbavboa, Urule; Müller, Walter E; Eckert, Gunter P

2011-03-01

Lipids are essential for the structural and functional integrity of membranes. Membrane lipids are not randomly distributed but are localized in different domains. A common characteristic of these membrane domains is their association with cholesterol. Lipid rafts and caveolae are examples of cholesterol enriched domains, which have attracted keen interest. However, two other important cholesterol domains are the exofacial and cytofacial leaflets of the plasma membrane. The two leaflets that make up the bilayer differ in their fluidity, electrical charge, lipid distribution, and active sites of certain proteins. The synaptic plasma membrane (SPM) cytofacial leaflet contains over 85% of the total SPM cholesterol as compared with the exofacial leaflet. This asymmetric distribution of cholesterol is not fixed or immobile but can be modified by different conditions in vivo: (i) chronic ethanol consumption; (ii) statins; (iii) aging; and (iv) apoE isoform. Several potential candidates have been proposed as mechanisms involved in regulation of SPM cholesterol asymmetry: apoE, low-density lipoprotein receptor, sterol carrier protein-2, fatty acid binding proteins, polyunsaturated fatty acids, P-glycoprotein and caveolin-1. This review examines cholesterol asymmetry in SPM, potential mechanisms of regulation and impact on membrane structure and function. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

Use of isothermal titration calorimetry to study the interaction of short-chain alcohols with lipid membranes

DEFF Research Database (Denmark)

Trandum, Christa; Westh-Andersen, Peter; Jørgensen, Kent

1999-01-01

of short-chain alcohols on Lipid bilayers. isothermal titration calorimetry (ITC) has been used to determine the energy involved in the association of the alcohols with lipid bilayers. Pure unilamellar DMPC liposomes and DMPC liposomes incorporated with different amounts of cholesterol, sphingomyelin...... dependent on the lipid bilayer composition. In the presence of high concentrations of cholesterol, the binding enthalpy of ethanol is decreased, whereas the presence of ceramides enhances the enthalpic response of the lipid bilayer to ethanol. Isothermal titration calorimetry offers a new methodology...

Impact of ticagrelor on P2Y1 and P2Y12 localization and on cholesterol levels in platelet plasma membrane.

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Rabani, Vahideh; Montange, Damien; Meneveau, Nicolas; Davani, Siamak

2017-10-11

Ticagrelor is an antiplatelet agent that inhibits platelet activation via P2Y12 antagonism. There are several studies showing that P2Y12 needs lipid rafts to be activated, but there are few data about how ticagrelor impacts lipid raft organization. Therefore, we aimed to investigate how ticagrelor could impact the distribution of cholesterol and consequently alter the organization of lipid rafts on platelet plasma membranes. We identified cholesterol-enriched raft fractions in platelet membranes by quantification of their cholesterol levels. Modifications in cholesterol and protein profiles (Flotillin 1, Flotillin 2, CD36, P2Y1, and P2Y12) were studied in platelets stimulated by ADP, treated by ticagrelor, or both. In ADP-stimulated and ticagrelor-treated groups, we found a decreased level of cholesterol in raft fractions of platelet plasma membrane compared to the control group. In addition, the peak of cholesterol in different experimental groups changed its localization on membrane fractions. In the control group, it was situated on fraction 2, while in ADP-stimulated platelets, it was located in fractions 3 to 5, and in fraction 4 in ticagrelor-treated group. The proteins studied also showed changes in their level of expression and localization in fractions of plasma membrane. Cholesterol levels of plasma membranes have a direct role in the organization of platelet membranes and could be modified by stimulation or drug treatment. Since ticagrelor and ADP both changed lipid composition and protein profile, investigating the lipid and protein composition of platelet membranes is of considerable importance as a focus for further research in anti-platelet management.

[Cholesterol metabolism and lipid peroxidation processes in hypodynamia. Effect of using ascorbic acid and alpha-tocopherol].

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Elikov, A V; Tsapok, P I

2010-01-01

Study status of cholesterol metabolism, processes of lipid peroxidation and antioxidant protection in blood plasma, erythrocytes and homogenates of the, heart, liver, muscle femors of rats attached to movement active. Establishment effects application of ascorbic acid and alpha-tocopherol. Ascorbic acid and alpha-tocopherol were infused daily. The daily dosage was 2 and 1 mg respectively. Characteristic shift changes of cholesterol metabolism in conditions of limited muscular activity were revealed. It was shown that vitamin antioxidants play a role in correction of metabolic disorders in case of immobile distress syndrome.

Influence of low cholesterol eggs enriched with vitamin-E and omega-3 fatty acid on blood lipid profile of Wistar rats.

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Taneja, S K; Rakha, Aruna

2005-07-01

In the recent past, low cholesterol eggs enriched with vitamin-E and omega-3 fatty acid have been developed and are marketed under different brands claiming them as heart friendly. The influence of these eggs (smart eggs) on lipid profile of rats was evaluated in comparison to that of the standard eggs. Data of 4 week dietary treatment revealed that total plasma cholesterol, low density lipoprotein (LDL) and very low density lipoprotein (VLDL) cholesterol increased only 22% in rats fed on diet containing 4 smart eggs per kg of semi-synthetic diet in contrast to the increase of more than 100 % when fed on diet containing standard eggs. The results suggest that it is not the low cholesterol content alone but also vitamin E and omega-3 fatty acids present in smart eggs that act synergically to prevent a substantial change in blood lipid profile and impose no serious risk to the health of the consumers.

Modulation by geraniol of gene expression involved in lipid metabolism leading to a reduction of serum-cholesterol and triglyceride levels.

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Galle, Marianela; Kladniew, Boris Rodenak; Castro, María Agustina; Villegas, Sandra Montero; Lacunza, Ezequiel; Polo, Mónica; de Bravo, Margarita García; Crespo, Rosana

2015-07-15

Geraniol (G) is a natural isoprenoid present in the essential oils of several aromatic plants, with various biochemical and pharmacologic properties. Nevertheless, the mechanisms of action of G on cellular metabolism are largely unknown. We propose that G could be a potential agent for the treatment of hyperlipidemia that could contribute to the prevention of cardiovascular disease. The aim of the present study was to advance our understanding of its mechanism of action on cholesterol and TG metabolism. NIH mice received supplemented diets containing 25, 50, and 75 mmol G/kg chow. After a 3-week treatment, serum total-cholesterol and triglyceride levels were measured by commercial kits and lipid biosynthesis determined by the [(14)C] acetate incorporated into fatty acids plus nonsaponifiable and total hepatic lipids of the mice. The activity of the mRNA encoding HMGCR-the rate-limiting step in cholesterol biosynthesis-along with the enzyme levels and catalysis were assessed by real-time RT-PCR, Western blotting, and HMG-CoA-conversion assays, respectively. In-silico analysis of several genes involved in lipid metabolism and regulated by G in cultured cells was also performed. Finally, the mRNA levels encoded by the genes for the low-density-lipoprotein receptor (LDLR), the sterol-regulatory-element-binding transcription factor (SREBF2), the very-low-density-lipoprotein receptor (VLDLR), and the acetyl-CoA carboxylase (ACACA) were determined by real-time RT-PCR. Plasma total-cholesterol and triglyceride levels plus hepatic fatty-acid, total-lipid, and nonsaponifiable-lipid biosynthesis were significantly reduced by feeding with G. Even though an up-regulation of the mRNA encoding HMGCR occurred in the G treated mouse livers, the protein levels and specific activity of the enzyme were both inhibited. G also enhanced the mRNAs encoding the LDL and VLDL receptors and reduced ACACA mRNA, without altering the transcription of the mRNA encoding the SREBF2. The following

Key molecular requirements for raft formation in lipid/cholesterol membranes.

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Davit Hakobyan

Full Text Available The lipid mixture of DPPC (saturated lipid/DUPC (unsaturated lipid/CHOL (cholesterol is studied with respect to its ability to form liquid-ordered and liquid-disordered phases. We employ coarse-grained simulations with MARTINI force field. All three components are systematically modified in order to explore the relevant molecular properties, leading to phase separation. Specifically, we show that the DPPC/DUPC/CHOL system unmixes due to enthalpic DPPC-DPPC and DPPC-CHOL interactions. The phase separation remains unchanged, except for the formation of a gel phase at long times after decreasing the conformational degrees of freedom of the unsaturated DUPC. In contrast, the phase separation can be suppressed by softening the DPPC chains. In an attempt to mimic the ordering and unmixing effect of CHOL the latter is replaced by a stiff and shortened DPPC-like lipid. One still observes phase separation, suggesting that it is mainly the rigid and planar structure of CHOL which is important for raft formation. Addition of an extra bead to the head of CHOL has no notable impact on the phase separation of the system, supporting the irrelevance of the Umbrella model for the phase separation. Reduction of the conformational entropy of CHOL by stiffening its last bead results in a significant increase of the order of the DPPC/CHOL domain. This suggests that the conformational entropy of CHOL is important to prohibit the gelation process. The interleaflet interactions as mediated by the terminal molecular groups seem to have a strong impact on the possibility of a subsequent gelation process after phase separation.

Genetic polymorphisms in carnitine palmitoyltransferase 1A gene are associated with variation in body composition and fasting lipid traits in Yup'ik Eskimos[S

Science.gov (United States)

Lemas, Dominick J.; Wiener, Howard W.; O'Brien, Diane M.; Hopkins, Scarlett; Stanhope, Kimber L.; Havel, Peter J.; Allison, David B.; Fernandez, Jose R.; Tiwari, Hemant K.; Boyer, Bert B.

2012-01-01

Variants of carnitine palmitoyltransferase 1A (CPT1A), a key hepatic lipid oxidation enzyme, may influence how fatty acid oxidation contributes to obesity and metabolic outcomes. CPT1A is regulated by diet, suggesting interactions between gene variants and diet may influence outcomes. The objective of this study was to test the association of CPT1A variants with body composition and lipids, mediated by consumption of polyunsaturated fatty acids (PUFA). Obesity phenotypes and fasting lipids were measured in a cross-sectional sample of Yup'ik Eskimo individuals (n = 1141) from the Center of Alaska Native Health Research (CANHR) study. Twenty-eight tagging CPT1A SNPs were evaluated with outcomes of interest in regression models accounting for family structure. Several CPT1A polymorphisms were associated with HDL-cholesterol and obesity phenotypes. The P479L (rs80356779) variant was associated with all obesity-related traits and fasting HDL-cholesterol. Interestingly, the association of P479L with HDL-cholesterol was still significant after correcting for body mass index (BMI), percentage body fat (PBF), or waist circumference (WC). Our findings are consistent with the hypothesis that the L479 allele of the CPT1A P479L variant confers a selective advantage that is both cardioprotective (through increased HDL-cholesterol) and associated with reduced adiposity. PMID:22045927

In vitro and in vivo effects of polyethylene glycol (PEG)-modified lipid in DOTAP/cholesterol-mediated gene transfection

DEFF Research Database (Denmark)

Gjetting, Torben; Arildsen, Nicolai Skovbjerg; Christensen, Camilla Laulund

2010-01-01

DOTAP/cholesterol-based lipoplexes are successfully used for delivery of plasmid DNA in vivo especially to the lungs, although low systemic stability and circulation have been reported. To achieve the aim of discovering the best method for systemic delivery of DNA to disseminated tumors we evalua...... evaluated the potential of formulating DOTAP/cholesterol lipoplexes with a polyethylene glycol (PEG)-modified lipid, giving the benefit of the shielding and stabilizing properties of PEG in the bloodstream....

DSC and EPR investigations on effects of cholesterol component on molecular interactions between paclitaxel and phospholipid within lipid bilayer membrane.

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Zhao, Lingyun; Feng, Si-Shen; Kocherginsky, Nikolai; Kostetski, Iouri

2007-06-29

Differential scanning calorimetry (DSC) and electron paramagnetic resonance spectroscopy (EPR) were applied to investigate effects of cholesterol component on molecular interactions between paclitaxel, which is one of the best antineoplastic agents found from nature, and dipalmitoylphosphatidylcholine (DPPC) within lipid bilayer vesicles (liposomes), which could also be used as a model cell membrane. DSC analysis showed that incorporation of paclitaxel into the DPPC bilayer causes a reduction in the cooperativity of bilayer phase transition, leading to a looser and more flexible bilayer structure. Including cholesterol component in the DPPC/paclitaxel mixed bilayer can facilitate the molecular interaction between paclitaxel and lipid and make the tertiary system more stable. EPR analysis demonstrated that both of paclitaxel and cholesterol have fluidization effect on the DPPC bilayer membranes although cholesterol has more significant effect than paclitaxel does. The reduction kinetics of nitroxides by ascorbic acid showed that paclitaxel can inhibit the reaction by blocking the diffusion of either the ascorbic acid or nitroxide molecules since the reaction is tested to be a first order one. Cholesterol can remarkably increase the reduction reaction speed. This research may provide useful information for optimizing liposomal formulation of the drug as well as for understanding the pharmacology of paclitaxel.

Understanding physician and consumer attitudes concerning cholesterol management: results from the National Lipid Association surveys.

Science.gov (United States)

Pasternak, Richard C; McKenney, James M; Brown, W Virgil; Cahill, Edward; Cohen, Jerome D

2004-11-04

Two online surveys commissioned by the National Lipid Association (NLA) were conducted to determine the current attitudes of physicians and consumers regarding cholesterol and heart disease. Physicians and consumers from preexisting independent panels were randomly invited to participate in the online surveys that were open from January 26 to 30, 2004. Both physicians (n = 200) and consumers (n = 600) agreed that high cholesterol and coronary artery disease (CAD) are significant health risks. Physicians reported the primary barriers for patients being prescribed cholesterol-lowering medication as patient fear of side effects (61%) and reluctance to take prescription medications (52%). While most physicians were aware of and felt they adhered to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) guidelines, considerably fewer thought the same of other physicians. The consumer survey focused on untreated moderate-risk patients (an approximate 10% to 20% 10-year risk of myocardial infarction and cardiac death) because this group is often undertreated. Untreated moderate-risk patients reported that their physicians did not advise them to take prescription cholesterol-lowering drugs (51%) and that they were trying to control their cholesterol with diet and exercise (58%). Consumers believe they are taking an increased role in their own health management and decision making. Current attitudes of physicians and consumers are similar with regard to their recognition of the significance of cholesterol and CAD for health, but differ with regard to why patients do not take prescription medications.

Study of the Combined Effect of Ibuprofen and Cholesterol on the Microviscosity and Ordering of Model Lipid Membranes by Timeresolved Measurement of Fluorescence Anisotropy Decay

Science.gov (United States)

Yefimova, S. L.; Tkacheva, T. N.; Kasian, N. A.

2017-05-01

The timeresolved fluorescence anisotropy decay of perylene incorporated into the lipid Ladipalmitoylphosphatidylch oline (DPPC) membrane has been studied to evaluate the membranotropic action of the nonsteroidal antiinflammatory drug, ibuprofen, and the combined effect of ibuprofen and cholesterol. The rotation correlation times (φ) and limiting anisotropy (r∞ ) permit an independent estimation of the effects of these additives on the microviscosity and ordering of model lipid membranes in different phase states. Ibuprofen was shown to cause a significant decrease in the DPPC membrane microviscosity in the gel phase with hardly any effect on the liquidcrystal phase. However, in both phases, ibuprofen diminishes the ordering of the lipid hydrophobic chains. A marked additive effect is noted when ibuprofen is embedded in the liquid membrane enriched with cholesterol, which manifests itself in substantial fluidization and disordering or the liquid membrane by the action of the components on the lipid membrane. Ibuprofen in the liquidcrystal phase causes leveling of the fluidizing and ordering effects of cholesterol.

Lipid Bilayer Composition Affects Transmembrane Protein Orientation and Function

Directory of Open Access Journals (Sweden)

Katie D. Hickey

2011-01-01

Full Text Available Sperm membranes change in structure and composition upon ejaculation to undergo capacitation, a molecular transformation which enables spermatozoa to undergo the acrosome reaction and be capable of fertilization. Changes to the membrane environment including lipid composition, specifically lipid microdomains, may be responsible for enabling capacitation. To study the effect of lipid environment on proteins, liposomes were created using lipids extracted from bull sperm membranes, with or without a protein (Na+ K+-ATPase or -amylase. Protein incorporation, function, and orientation were determined. Fluorescence resonance energy transfer (FRET confirmed protein inclusion in the lipid bilayer, and protein function was confirmed using a colourometric assay of phosphate production from ATP cleavage. In the native lipid liposomes, ATPase was oriented with the subunit facing the outer leaflet, while changing the lipid composition to 50% native lipids and 50% exogenous lipids significantly altered this orientation of Na+ K+-ATPase within the membranes.

Statistical evaluation of fatty acid profile and cholesterol content in fish (common carp) lipids obtained by different sample preparation procedures.

Science.gov (United States)

Spiric, Aurelija; Trbovic, Dejana; Vranic, Danijela; Djinovic, Jasna; Petronijevic, Radivoj; Matekalo-Sverak, Vesna

2010-07-05

Studies performed on lipid extraction from animal and fish tissues do not provide information on its influence on fatty acid composition of the extracted lipids as well as on cholesterol content. Data presented in this paper indicate the impact of extraction procedures on fatty acid profile of fish lipids extracted by the modified Soxhlet and ASE (accelerated solvent extraction) procedure. Cholesterol was also determined by direct saponification method, too. Student's paired t-test used for comparison of the total fat content in carp fish population obtained by two extraction methods shows that differences between values of the total fat content determined by ASE and modified Soxhlet method are not statistically significant. Values obtained by three different methods (direct saponification, ASE and modified Soxhlet method), used for determination of cholesterol content in carp, were compared by one-way analysis of variance (ANOVA). The obtained results show that modified Soxhlet method gives results which differ significantly from the results obtained by direct saponification and ASE method. However the results obtained by direct saponification and ASE method do not differ significantly from each other. The highest quantities for cholesterol (37.65 to 65.44 mg/100 g) in the analyzed fish muscle were obtained by applying direct saponification method, as less destructive one, followed by ASE (34.16 to 52.60 mg/100 g) and modified Soxhlet extraction method (10.73 to 30.83 mg/100 g). Modified Soxhlet method for extraction of fish lipids gives higher values for n-6 fatty acids than ASE method (t(paired)=3.22 t(c)=2.36), while there is no statistically significant difference in the n-3 content levels between the methods (t(paired)=1.31). The UNSFA/SFA ratio obtained by using modified Soxhlet method is also higher than the ratio obtained using ASE method (t(paired)=4.88 t(c)=2.36). Results of Principal Component Analysis (PCA) showed that the highest positive impact to

Combined effect of cooking (grilling and roasting) and chilling storage (with and without air) on lipid and cholesterol oxidation in chicken breast.

Science.gov (United States)

Conchillo, Ana; Ansorena, Diana; Astiasarán, Iciar

2003-05-01

The oxidation of the lipid fraction and cholesterol in raw and cooked chicken breast samples stored for 0 and 6 days at 4 degrees C under aerobic conditions and in vacuum packaging was studied. The multivariate statistical analysis showed significant effects of both culinary process and storage conditions on the lipid and cholesterol oxidation process, with a significant interaction between the two variables. Aerobic storage increased thiobarbituric acid reactive substances (TBA) from 0.04 to 0.06 ppm for raw samples, from 0.21 to 1.20 ppm for grilled samples, and from 0.24 to 1.62 ppm for roasted samples. During vacuum storage, only roasted samples showed significant increases in TBA. Levels of total cholesterol oxidation products (COP) remained low (2.88 to 4.35 microg/g of lipid) for all raw samples. Cooking increased COP levels to 12.85 and 11.54 microg/ g of lipid for grilled and roasted samples, respectively. Total COP and all individual COP except for cholestanetriol were significantly correlated with TBA and the peroxide index. However, the most extensive effect was attributable to the aerobic storage of cooked samples, which led to COP levels of 92.35 and 88.60 microg/g of lipid in grilled and roasted samples, respectively. Vacuum packaging did not increase COP levels for cooked samples.

Proximate and Cholesterol Composition of Selected Fast Foods ...

African Journals Online (AJOL)

Fast foods consumption has been on the increase in Nigeria raising concerns about the nutritional and health implications. This study was carried out to determine the proximate composition and cholesterol contents of four commonly consumed fast foods (doughnut, chicken pie, roasted chicken, and Jollof rice) sold in ...

[Effect of a new low-cholesterol meat and vegetal product on correction of simulated lipid metabolism disorders in rats].

Science.gov (United States)

Gorlov, I F; Slozhenkina, M I; Karpenko, E V; Giro, T M; Andreeva, S V

2015-01-01

The paper presents the biomedical evaluation of meat and cereal spread from low-cholesterol raw material with vegetable ingredients, recommended as a functional food. The experimental model with myocardial infarction like changes in hearts of the animals, accompanied by vascular changes similar to atherosclerotic changes in humans, as well as the modeling of the metabolic imbalance of lipids have been carried out by intramuscular injection of epinephrine and unbalanced feeding the animals with food rich in cholesterol, with a high content of carbohydrates and fats. Wistar rats were divided into 4 groups of 12 animals each. The rats in groups 1-3 were induced the cardio distress with intramuscular injection of epinephrine; group IV consisted of intact (healthy) animals. Dramatic changes in biochemical blood status that indicated heart disease have been observed within 2 days after the injection of epinephrine (0.2 ml per 1 kg of animal body weight) to the tested animals. During the experiment a sharp increase in activity of indicator enzymes of alanine aminotransferase (ALT) and aspartate aminotransferases (AST), with a predominance of AST over ALT, along with an increase in LDH activity have been observed. The 1.4-1.6 fold increase in blood serum creatinine has also been found. Later the animals in groups 1, 2, 3 with simulated cardio pathology were fed a ration with intervention of food rich in cholesterol, with a high content of carbohydrates and fats (50% of the diet) for a month for induction of lipid metabolism disorders. An increase in the concentration of cholesterol and triglycerides by 3 fold or more has been observed. In addition, an accumulation of sulfhydryl groups has been noted, as evidenced by increased rates of thymol. For further normalization of lipid metabolism, the animals in tested group I were fed the diet with intervention of spread, developed in accordance with GOST 12318-91 "Canned meat "Meat spread"; the rats of group 2 were fed with

The tuber extract and flour of Dioscorea alatanormalize the blood lipid profile of rabbits treated with high cholesterol diets

Directory of Open Access Journals (Sweden)

Nelis Imanningsih

2014-08-01

rabbits treated with high cholesterol diets.Methods:DA tuber extract and flour were administrated to the rabbits for 60 days using completely randomised design. The ration treatment are as follows: 1 Basal ration as negative control (K0, 2 Basal ration + 0.5% cholesterol, as positive control (K1, 3 Basal ration + 0.5% cholesterol + DA extract 1.8 g/100 g (KE1, 4 Basal ration + cholesterol 0.5% + DA extract 3.6 g/100 g (KE2, 5 Basal ration with 15% DA flour + 0.5% cholesterol (KT1 and 6 Basal ration with 30% DA flour + 0.5% cholesterol (KT2. The Total cholesterol, HDL, LDL cholesterol in serum were analysed at baseline, days 28, days 56 and at the end of study.Results:The administration of high cholesterol (1% ration increased blood lipid levels by 16 fold compared to that of control. The administration of 15% and 30% of DA flour could maintain blood lipid profile to normal condition, in particular at 30% substitution DA flour. However the water extract of DA can not maintain a normal blood lipids of high cholesterol treated rabbitsConclusion: Dioscorea alata flour has suggested to have anti-hyperlipidemia effect. (Health Science Indones 2014;1:23-9Key words: Dioscorea alata, hyperlipidemia, atherosclerosis

A Quantitative Systems Pharmacology Platform to Investigate the Impact of Alirocumab and Cholesterol-Lowering Therapies on Lipid Profiles and Plaque Characteristics

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Jeffrey E Ming

2017-06-01

Full Text Available Reduction in low-density lipoprotein cholesterol (LDL-C is associated with decreased risk for cardiovascular disease. Alirocumab, an antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9, significantly reduces LDL-C. Here, we report development of a quantitative systems pharmacology (QSP model integrating peripheral and liver cholesterol metabolism, as well as PCSK9 function, to examine the mechanisms of action of alirocumab and other lipid-lowering therapies, including statins. The model predicts changes in LDL-C and other lipids that are consistent with effects observed in clinical trials of single or combined treatments of alirocumab and other treatments. An exploratory model to examine the effects of lipid levels on plaque dynamics was also developed. The QSP platform, on further development and qualification, may support dose optimization and clinical trial design for PCSK9 inhibitors and lipid-modulating drugs. It may also improve our understanding of factors affecting therapeutic responses in different phenotypes of dyslipidemia and cardiovascular disease.

Effect of Grape Seeds Oil Extracted from Radiation Processed Seeds on Lipid Metabolism and on Antioxidant Activity in Rats Fed Diets Containing Cholesterol

International Nuclear Information System (INIS)

El-Neily, H.F.G.; El-Shennawy, H.M.

2011-01-01

Grape seeds were separated from fresh grape pomace and dried at room temperature then packed in polyethylene bags and subjected to gamma rays at dose level of 10 kGy. The grape seeds oil was extracted from non and irradiated seeds. The oil quality, fatty acid composition and total phenolic compounds of oil extracted from non or irradiated seeds have been studied. The results indicated that there were significant increases in the acid value, saponification value and peroxide value of oil extracted from irradiated seeds at 10 kGy by 46.2%, 2.5% and 95.2%, respectively, and the total phenolic compounds and total radical trapping antioxidant potential (TRAP) were reduced by 22.13% and 10%, respectively, as compared to those of oil extracted from non-irradiated seeds. No degradation of the fatty acids; palmitic, linoleic, linolenic and arachidic acids, were observed for oil extracted from irradiated seeds at 10 kGy. However, significant decrease in oleic acid by 11.35% and increase in stearic acid by 26.22% were recorded corresponding to those for oil extracted from non-irradiated seeds. The effect of grape seeds oils extracted from non or irradiated seeds on lipid metabolism and antioxidant activity was investigated using 60 male Albino rats divided into six groups: (1) Control group: animals fed casein diet. (2) Ch group: animals received casein diet contains 10 g cholesterol per kg diet. (3) RGSO group: animals received diet contains grape seeds oil extracted from non-irradiated seeds (100 g oil per kg diet). (4) RGSO + Ch group: rats received diet contains grape seeds oil extracted from non-irradiated seeds (100 g oil per kg diet) + 100 g cholesterol per kg diet. (5) IGSO group: rats received diet contains grape seeds oil extracted from irradiated seeds at 10 kGy (100 g oil per kg diet). (6) IGSO + Ch group: rats received diet contains grape seeds oil extracted from irradiated seeds at 10 kGy (100 g oil per kg diet) + 10 g cholesterol per kg diet. Animals received

Engineering the lipid layer of lipid-PLGA hybrid nanoparticles for enhanced in vitro cellular uptake and improved stability.

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Hu, Yun; Hoerle, Reece; Ehrich, Marion; Zhang, Chenming

2015-12-01

Lipid-polymer hybrid nanoparticles (NPs), consisting of a polymeric core and a lipid shell, have been intensively examined as delivery systems for cancer drugs, imaging agents, and vaccines. For applications in vaccine particularly, the hybrid NPs need to be able to protect the enclosed antigens during circulation, easily be up-taken by dendritic cells, and possess good stability for prolonged storage. However, the influence of lipid composition on the performance of hybrid NPs has not been well studied. In this study, we demonstrate that higher concentrations of cholesterol in the lipid layer enable slower and more controlled antigen release from lipid-poly(lactide-co-glycolide) acid (lipid-PLGA) NPs in human serum and phosphate buffered saline (PBS). Higher concentrations of cholesterol also promoted in vitro cellular uptake of hybrid NPs, improved the stability of the lipid layer, and protected the integrity of the hybrid structure during long-term storage. However, stabilized hybrid structures of high cholesterol content tended to fuse with each other during storage, resulting in significant size increase and lowered cellular uptake. Additional experiments demonstrated that PEGylation of NPs could effectively minimize fusion-caused size increase after long term storage, leading to improved cellular uptake, although excessive PEGylation will not be beneficial and led to reduced improvement. This paper reports the engineering of the lipid layer that encloses a polymeric nanoparticle, which can be used as a carrier for drug and vaccine molecules for targeted delivery. We demonstrated that the concentration of cholesterol is critical for the stability and uptake of the hybrid nanoparticles by dendritic cells, a targeted cell for the delivery of immune effector molecules. However, we found that hybrid nanoparticles with high cholesterol concentration tend to fuse during storage resulting in larger particles with decreased cellular uptake. This problem is

Lipid-load in peripheral blood mononuclear cells: Impact of food-consumption, dietary-macronutrients, extracellular lipid availability and demographic factors.

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Ameer, Fatima; Munir, Rimsha; Usman, Hina; Rashid, Rida; Shahjahan, Muhammad; Hasnain, Shahida; Zaidi, Nousheen

2017-04-01

Lipid-load in peripheral blood mononuclear cells (PBMCs) has recently gained attention of the researchers working on nutritional regulation of metabolic health. Previous works have indicated that the metabolic circuitries in the circulating PBMCs are influenced by dietary-intake and macronutrient composition of diet. In the present work, we analyzed the impact of diet and dietary macronutrients on PBMCs' lipid-load. The overall analyses revealed that dietary carbohydrates and fats combinatorially induce triglyceride accumulation in PBMCs. On the other hand, dietary fats were shown to induce significant decrease in PBMCs' cholesterol-load. The effects of various demographic factors -including age, gender and body-weight- on PBMCs' lipid-load were also examined. Body-weight and age were both shown to affect PBMC's lipid-load. Our study fails to provide any direct association between extracellular lipid availability and cholesterol-load in both, freshly isolated and cultured PBMCs. The presented work significantly contributes to the current understanding of the impact of food-consumption, dietary macronutrients, extracellular lipid availability and demographic factors on lipid-load in PBMCs. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Plasma cholesterol and endogenous cholesterol synthesis during refeeding in anorexia nervosa.

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Feillet, F; Feillet-Coudray, C; Bard, J M; Parra, H J; Favre, E; Kabuth, B; Fruchart, J C; Vidailhet, M

2000-04-01

Normal or high levels of cholesterol have been measured in patients with anorexia nervosa (AN). Given that cholesterol intake in AN is usually very low, the reasons for this anomaly are not clearly understood. We studied lipid and lipoprotein profiles and endogenous cholesterol synthesis, estimated by serum lathosterol, in a population of 14 girls with AN, before and during a period of 30 days refeeding. The initial body mass index (BMI) of the patients was 13.41+/-1.62 kg/m(2). No changes were observed during refeeding in endocrine parameters (ACTH, cortisol and estradiol). At Day 0 the lipids data measured here showed normal levels of triglycerides, and total cholesterol at the upper limits of the normal range (5.44+/-1 mmol/l). At this time, total and LDL cholesterol were negatively correlated with transthyretin and BMI. Serum lathosterol (a precursor in cholesterol synthesis pathway) increased significantly (5.99+/-1.75 (Day 0) vs. 8.39+/-2.96 (Day 30); P=0.02) while there was a significant decrease in apo B (0.79+/-0.33 (Day 0) vs. 0. 60+/-0.17 g/l (Day 30), P=0.02) with refeeding. Thus, patients with initial high cholesterol levels have the worst nutritional status and high cholesterol levels are not related to a de novo synthesis. This profile returns to normal with refeeding. An increase of cellular cholesterol uptake may be responsible for this apparently paradoxical evolution with increase of cholesterol synthesis and decrease of apo B during renutrition.

Lipid clustering correlates with membrane curvature as revealed by molecular simulations of complex lipid bilayers.

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Heidi Koldsø

2014-10-01

Full Text Available Cell membranes are complex multicomponent systems, which are highly heterogeneous in the lipid distribution and composition. To date, most molecular simulations have focussed on relatively simple lipid compositions, helping to inform our understanding of in vitro experimental studies. Here we describe on simulations of complex asymmetric plasma membrane model, which contains seven different lipids species including the glycolipid GM3 in the outer leaflet and the anionic lipid, phosphatidylinositol 4,5-bisphophate (PIP2, in the inner leaflet. Plasma membrane models consisting of 1500 lipids and resembling the in vivo composition were constructed and simulations were run for 5 µs. In these simulations the most striking feature was the formation of nano-clusters of GM3 within the outer leaflet. In simulations of protein interactions within a plasma membrane model, GM3, PIP2, and cholesterol all formed favorable interactions with the model α-helical protein. A larger scale simulation of a model plasma membrane containing 6000 lipid molecules revealed correlations between curvature of the bilayer surface and clustering of lipid molecules. In particular, the concave (when viewed from the extracellular side regions of the bilayer surface were locally enriched in GM3. In summary, these simulations explore the nanoscale dynamics of model bilayers which mimic the in vivo lipid composition of mammalian plasma membranes, revealing emergent nanoscale membrane organization which may be coupled both to fluctuations in local membrane geometry and to interactions with proteins.

Cholesterol in unusual places

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Kucerka, N; Nieh, M P; Marquardt, D; Harroun, T A; Wassail, S R; Katsaras, J, E-mail: John.Katsaras@nrc.gc.ca, E-mail: Norbert.Kucerka@nrc.gc.ca

2010-11-01

Cholesterol is an essential component of mammalian cells, and is required for building and maintaining cell membranes, regulating their fluidity, and possibly acting as an antioxidant. Cholesterol has also been implicated in cell signaling processes, where it has been suggested that it triggers the formation of lipid rafts in the plasma membrane. Aside from cholesterol's physiological roles, what is also becoming clear is its poor affinity for lipids with unsaturated fatty acids as opposed to saturated lipids, such as sphingomyelin with which it forms rafts. We previously reported the location of cholesterol in membranes with varying degrees of acyl chain unsaturation as determined by neutron diffraction studies (Harroun et al 2006 Biochemistry 45, 1227; Harroun et al 2008 Biochemistry 47, 7090). In bilayers composed of phosphatidylcholine (PC) molecules with a saturated acyl chain at the sn-1 position or a monounsaturated acyl chain at both sn-1 and sn-2 positions, cholesterol was found in its much-accepted 'upright' position. However, in dipolyunsaturated 1,2-diarachidonyl phosphatidylcholine (20:4-20:4PC) membranes the molecule was found sequestered in the center of the bilayers. In further experiments, mixing l-palmitoyl-2-oleoyl phosphatidylcholine (16:0-18:1 PC) with 20:4-20:4PC resulted in cholesterol reverting to its upright orientation at approximately 40 mol% 16:0-18:1 PC. Interestingly, the same effect was achieved with only 5 mol% 1,2-dimyristoyl phosphatidylchoile (14:0-14:0PC).

Cholesterol in unusual places

International Nuclear Information System (INIS)

Kucerka, N; Nieh, M P; Marquardt, D; Harroun, T A; Wassail, S R; Katsaras, J

2010-01-01

Cholesterol is an essential component of mammalian cells, and is required for building and maintaining cell membranes, regulating their fluidity, and possibly acting as an antioxidant. Cholesterol has also been implicated in cell signaling processes, where it has been suggested that it triggers the formation of lipid rafts in the plasma membrane. Aside from cholesterol's physiological roles, what is also becoming clear is its poor affinity for lipids with unsaturated fatty acids as opposed to saturated lipids, such as sphingomyelin with which it forms rafts. We previously reported the location of cholesterol in membranes with varying degrees of acyl chain unsaturation as determined by neutron diffraction studies (Harroun et al 2006 Biochemistry 45, 1227; Harroun et al 2008 Biochemistry 47, 7090). In bilayers composed of phosphatidylcholine (PC) molecules with a saturated acyl chain at the sn-1 position or a monounsaturated acyl chain at both sn-1 and sn-2 positions, cholesterol was found in its much-accepted 'upright' position. However, in dipolyunsaturated 1,2-diarachidonyl phosphatidylcholine (20:4-20:4PC) membranes the molecule was found sequestered in the center of the bilayers. In further experiments, mixing l-palmitoyl-2-oleoyl phosphatidylcholine (16:0-18:1 PC) with 20:4-20:4PC resulted in cholesterol reverting to its upright orientation at approximately 40 mol% 16:0-18:1 PC. Interestingly, the same effect was achieved with only 5 mol% 1,2-dimyristoyl phosphatidylchoile (14:0-14:0PC).

Effect of soy protein on serum lipid profile and some lipid ...

African Journals Online (AJOL)

The effect of soy protein on serum lipid profile and some lipid metabolizing enzymes in rats fed with cholesterol diets was examined in this study. Rats were subjected to feeding trial over a period of six weeks on formulated diets containing: 20% soy protein with 0% cholesterol (group A), 20% soy protein with 5% cholesterol ...

A REVIEW ON CORRELATION BETWEEN LIPID PROFILE AND DEPRESSION

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Lalitha Devi Dhulipala

2016-07-01

Full Text Available Epidemiological and clinical intervention data indicate that low levels of circulating lipids and cholesterol are the risk factors for depressive symptoms. Olie et al 2011 (1 showed an association of low cholesterol and self-harm in their study. In the present scenario, depression and anxiety disorders have high prevalence rates and are frequently related. Understanding the subject and concepts/mechanisms related to neurobiological basis for these disorders is very important and the available techniques or methods are ineffective. Lipids generally play an important role in neural function in the brain. The composition of lipid of the brain influences perception, mood and behaviour. Lipids are responsible to regulate the membrane's function which acts as a barrier between the intracellular and extracellular spaces. It is found that membrane lipids determine the local behaviour and characterisation and function of proteins within the membrane. It is found from the literature that lipids can influence both exo-and endocytic processes and work within the membrane as second messengers. This paper discusses some important case studies related to the correlation between lipid profile and the depression.

Composition and biosynthesis of lipids in the healthy human skeletal muscle

International Nuclear Information System (INIS)

Schlenska, K.

1979-01-01

The skeletal muscle samples were ground in a Warburg Apparatus under oxygen, incubated for 20 to 120 min. at 37 0 C together with the three precursors of lipid biosynthesis, and oxygen uptake and 14 Co 2 -formation measured. Both parameters showed increasing values during the incubation time. The total lipid extract was isolated from the labelled skeletal muscle samples and was separated, following chromatographic purification on Sephatex-G 25 with the aid of thin-layer chromatography on silica gel, into the following fractions in order of decreasing concentration: phospholipids, triglycerides, cholesterol, mono- and diglyceride fraction, cholesterol ester fraction. Following in-vitro labelling with the three precursors, of the phospholipid fraction [ 3 H] palmilic and showed the highest, increasing incorporation rate, and [ 14 C] acetate the lowest level and slow rate of incorporation. For the central fat fraction labelling incorporation rate decreased in the order: monoglycerides > diglycerides > triglycerides. [ 14 C] acetate labelling occurred to a greater extent in cholestorol esters than in the cholestorol fraction. These findings indicate a de-novo biosynthesis of fatty acids from acetate and their incorporation in mono-, di-and triglycerides and in cholesterol ester. Moreover, incorporation of palmitic and in these fractions, de-novo synthesis of cholesterol, and incorporation of PO 4 3 - and labelled fatty acids in the phospholipid fraction are also suggested. (orig./MG) [de

Polar lipid composition of mammalian hair.

Science.gov (United States)

Wix, M A; Wertz, P W; Downing, D T

1987-01-01

The types and amounts of polar lipids from the hair of monkey (Macacca fascicularis), dog (Canis familiaris), pig (Sus scrofa) and porcupine (Erethizon dorsatum) have been determined by quantitative thin-layer chromatography. The polar lipid content of the hair samples ranged from 0.6 to 1.6 wt%. Lipid compositions included ceramides (57-63% of the polar lipid by weight), glycosphingolipids (7-9%) and cholesteryl sulfate (22-29%). Several minor components (4-7%) remain unidentified. The results suggest that cholesteryl sulfate may be an important determinant of the cohesiveness of hair.

General and specific lipid-protein interactions in Na,K-ATPase.

Science.gov (United States)

Cornelius, F; Habeck, M; Kanai, R; Toyoshima, C; Karlish, S J D

2015-09-01

The molecular activity of Na,K-ATPase and other P2 ATPases like Ca(2+)-ATPase is influenced by the lipid environment via both general (physical) and specific (chemical) interactions. Whereas the general effects of bilayer structure on membrane protein function are fairly well described and understood, the importance of the specific interactions has only been realized within the last decade due particularly to the growing field of membrane protein crystallization, which has shed new light on the molecular details of specific lipid-protein interactions. It is a remarkable observation that specific lipid-protein interactions seem to be evolutionarily conserved, and conformations of specifically bound lipids at the lipid-protein surface within the membrane are similar in crystal structures determined with different techniques and sources of the protein, despite the rather weak lipid-protein interaction energy. Studies of purified detergent-soluble recombinant αβ or αβFXYD Na,K-ATPase complexes reveal three separate functional effects of phospholipids and cholesterol with characteristic structural selectivity. The observations suggest that these three effects are exerted at separate binding sites for phophatidylserine/cholesterol (stabilizing), polyunsaturated phosphatidylethanolamine (stimulatory), and saturated PC or sphingomyelin/cholesterol (inhibitory), which may be located within three lipid-binding pockets identified in recent crystal structures of Na,K-ATPase. The findings point to a central role of direct and specific interactions of different phospholipids and cholesterol in determining both stability and molecular activity of Na,K-ATPase and possible implications for physiological regulation by membrane lipid composition. This article is part of a special issue titled "Lipid-Protein Interactions." Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of Melatonin and Cholesterol on the Structure of DOPC and DPPC Membranes

Energy Technology Data Exchange (ETDEWEB)

Drolle, E [University of Waterloo, Canada; Kucerka, Norbert [Canadian Neutron Beam Centre and Comelius University (Slovakia); Hoopes, M I [University of Waterloo, Canada; Choi, Y [University of Waterloo, Canada; Katsaras, John [ORNL; Karttunen, M [University of Waterloo, Canada; Leonenko, Z [University of Waterloo, Canada

2013-01-01

The cell membrane plays an important role in the molecular mechanism of amyloid toxicity associated with Alzheimer's disease. The membrane's chemical composition and the incorporation of small molecules, such as melatonin and cholesterol, can alter its structure and physical properties, thereby affecting its interaction with amyloid peptides. Both melatonin and cholesterol have been recently linked to amyloid toxicity. Melatonin has been shown to have a protective role against amyloid toxicity. However, the underlying molecular mechanism of this protection is still not well understood, and cholesterol's role remains controversial. We used small-angle neutron diffraction (SAND) from oriented lipid multi-layers, small-angle neutron scattering (SANS) from unilamellar vesicles experiments andMolecular Dynamics (MD) simulations to elucidate non-specific interactions of melatonin and cholesterol with 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 1,2-dipalmitoyl-snglycero-3-phosphocholine (DPPC) model membranes. We conclude that melatonin decreases the thickness of both model membranes by disordering the lipid hydrocarbon chains, thus increasing membrane fluidity. This result is in stark contrast to the much accepted ordering effect induced by cholesterol, which causes membranes to thicken.

Cholesterol transfer at endosomal-organelle membrane contact sites.

Science.gov (United States)

Ridgway, Neale D; Zhao, Kexin

2018-06-01

Cholesterol is delivered to the limiting membrane of late endosomes by Niemann-Pick Type C1 and C2 proteins. This review summarizes recent evidence that cholesterol transfer from endosomes to the endoplasmic reticulum and other organelles is mediated by lipid-binding proteins that localize to membrane contact sites (MCS). LDL-cholesterol in the late endosomal/lysosomes is exported to the plasma membrane, where most cholesterol resides, and the endoplasmic reticulum, which harbors the regulatory complexes and enzymes that control the synthesis and esterification of cholesterol. A major advance in dissecting these cholesterol transport pathways was identification of frequent and dynamic MCS between endosomes and the endoplasmic reticulum, peroxisomes and plasma membrane. Positioned at these MCS are members of the oxysterol-binding protein (OSBP) and steroidogenic acute regulatory protein-related lipid-transfer family of lipid transfer proteins that bridge the opposing membranes and directly or indirectly mediate cholesterol transfer. OSBP-related protein 1L (ORP1L), ORP5 and ORP6 mediate cholesterol transfer to the endoplasmic reticulum that regulates cholesterol homeostasis. ORP1L and STARD3 also move cholesterol from the endoplasmic reticulum-to-late endosomal/lysosomes under low-cholesterol conditions to facilitate intraluminal vesicle formation. Cholesterol transport also occurs at MCS with peroxisomes and possibly the plasma membrane. Frequent contacts between organelles and the endo-lysosomal vesicles are sites for bidirectional transfer of cholesterol.

Composição centesimal e teor de colesterol dos cortes comerciais de capivara (Hydrochaeris hydrochaeris L. 1766 Centesimal composition and cholesterol content in commercial cuts of capybaras (Hydrochaeris hydrochaeris L. 1766

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Sandra H. I. Oda

2004-12-01

Full Text Available Com o presente trabalho, objetivou-se determinar a composição centesimal e o teor de colesterol presente dos diferentes cortes comerciais da carne de capivara. A umidade, proteína, extrato etéreo e cinzas foram determinados segundo a AOAC (1990. O colesterol foi determinado por colorimetria. Os cortes comerciais apresentaram média de 75,80% de umidade; 21,74% de proteína; 0,74% de lipídios; 0,90% de cinzas; e 23,3 mg/100g de colesterol. Houve diferença (PThe aim of this work was to determine the proximate composition and cholesterol content in different commercial cuts of capybara. Moisture, crude fat, lipids and ash were determined following AOAC (1990 methods. Cholesterol content was determined by colorimetric method. Commercial cuts had values of: 75.8% of moisture; 21.74% of crude protein; 0.74% of crude fat; 0.90% of ash and 23.3mg/100g of cholesterol. There were significant (P<.05 differences on percentages of moisture and cholesterol content in the different commercial cuts. However, there was no difference on crude protein, crude fat and ash values. Results showed a lower percentage of lipids and cholesterol content in comparison with the meat of other species.

Variation in skin surface lipid composition among the Equidae.

Science.gov (United States)

Colton, S W; Downing, D T

1983-01-01

Skin surface lipids from Equus caballus, E. przewalskii, E. asinus, E. grevyi, E. hemionus onager and a mule (E. asinus/E. caballus) were analyzed in detail. In all species the surface lipid mixtures consisted of giant-ring lactones, cholesterol, cholesteryl esters and minor amounts of wax diesters. In E. caballus, the lactone hydroxyacids were entirely branched chained, while in E. asinus and E. grevyi they were almost exclusively straight chained. In E. przewalskii, the onager and the mule there were both straight and branched chain hydroxyacid lactones. These results are in harmony with published interpretations of the evolutionary relationships among Equus species.

Plasma kinetics of an LDL-like nanoemulsion and lipid transfer to HDL in subjects with glucose intolerance

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Marina P Bertato

2012-01-01

Full Text Available OBJECTIVE: Glucose intolerance is frequently associated with an altered plasma lipid profile and increased cardiovascular disease risk. Nonetheless, lipid metabolism is scarcely studied in normolipidemic glucose-intolerant patients. The aim of this study was to investigate whether important lipid metabolic parameters, such as the kinetics of LDL free and esterified cholesterol and the transfer of lipids to HDL, are altered in glucose-intolerant patients with normal plasma lipids. METHODS: Fourteen glucose-intolerant patients and 15 control patients were studied; none of the patients had cardiovascular disease manifestations, and they were paired for age, sex, race and co-morbidities. A nanoemulsion resembling a LDL lipid composition (LDE labeled with 14C-cholesteryl ester and ³H-free cholesterol was intravenously injected, and blood samples were collected over a 24-h period to determine the fractional clearance rate of the labels by compartmental analysis. The transfer of free and esterified cholesterol, triglycerides and phospholipids from the LDE to HDL was measured by the incubation of the LDE with plasma and radioactivity counting of the supernatant after chemical precipitation of non-HDL fractions. RESULTS: The levels of LDL, non-HDL and HDL cholesterol, triglycerides, apo A1 and apo B were equal in both groups. The 14C-esterified cholesterol fractional clearance rate was not different between glucose-intolerant and control patients, but the ³H-free-cholesterol fractional clearance rate was greater in glucose-intolerant patients than in control patients. The lipid transfer to HDL was equal in both groups. CONCLUSION: In these glucose-intolerant patients with normal plasma lipids, a faster removal of LDE free cholesterol was the only lipid metabolic alteration detected in our study. This finding suggests that the dissociation of free cholesterol from lipoprotein particles occurs in normolipidemic glucose intolerance and may participate in

Natural lipid extracts and biomembrane-mimicking lipid compositions are disposed to form nonlamellar phases, and they release DNA from lipoplexes most efficiently

Energy Technology Data Exchange (ETDEWEB)

Koynova, Rumiana; MacDonald, Robert C. (NWU)

2010-01-18

A viewpoint now emerging is that a critical factor in lipid-mediated transfection (lipofection) is the structural evolution of lipoplexes upon interacting and mixing with cellular lipids. Here we report our finding that lipid mixtures mimicking biomembrane lipid compositions are superior to pure anionic liposomes in their ability to release DNA from lipoplexes (cationic lipid/DNA complexes), even though they have a much lower negative charge density (and thus lower capacity to neutralize the positive charge of the lipoplex lipids). Flow fluorometry revealed that the portion of DNA released after a 30-min incubation of the cationic O-ethylphosphatidylcholine lipoplexes with the anionic phosphatidylserine or phosphatidylglycerol was 19% and 37%, respectively, whereas a mixture mimicking biomembranes (MM: phosphatidylcholine/phosphatidylethanolamine/phosphatidylserine /cholesterol 45:20:20:15 w/w) and polar lipid extract from bovine liver released 62% and 74%, respectively, of the DNA content. A possible reason for this superior power in releasing DNA by the natural lipid mixtures was suggested by structural experiments: while pure anionic lipids typically form lamellae, the natural lipid mixtures exhibited a surprising predilection to form nonlamellar phases. Thus, the MM mixture arranged into lamellar arrays at physiological temperature, but began to convert to the hexagonal phase at a slightly higher temperature, {approx} 40-45 C. A propensity to form nonlamellar phases (hexagonal, cubic, micellar) at close to physiological temperatures was also found with the lipid extracts from natural tissues (from bovine liver, brain, and heart). This result reveals that electrostatic interactions are only one of the factors involved in lipid-mediated DNA delivery. The tendency of lipid bilayers to form nonlamellar phases has been described in terms of bilayer 'frustration' which imposes a nonzero intrinsic curvature of the two opposing monolayers. Because the stored

Trends in lipid profiles and descriptive characteristics of U.S. adults with and without diabetes and cholesterol-lowering medication use-National Health and Nutrition Examination Survey, 2003-2012, United States.

Science.gov (United States)

Mercado, Carla I; Gregg, Edward; Gillespie, Cathleen; Loustalot, Fleetwood

2018-01-01

With a cholesterol-lowering focus for diabetic adults and in the age of polypharmacy, it is important to understand how lipid profile levels differ among those with and without diabetes. Investigate the means, differences, and trends in lipid profile measures [TC, total cholesterol; LDL-c, low-density lipoprotein; HDL-c, high-density lipoprotein; and TG, triglycerides] among US adults by diabetes status and cholesterol-lowering medication. Population number and proportion of adults aged ≥21 years with diabetes and taking cholesterol-lowering medication were estimated using data on 10,384 participants from NHANES 2003-2012. Age-standardized means, trends, and differences in lipid profile measures were estimated by diabetes status and cholesterol medication use. For trends and differences, linear regression analysis were used adjusted for age, gender, and race/ethnicity. Among diabetic adults, 52% were taking cholesterol-lowering medication compared to the 14% taking cholesterol-lowering medication without diabetes. Although diabetic adults had significantly lower TC and LDL-c levels than non-diabetic adults [% difference (95% confidence interval): TC = -5.2% (-6.8 --3.5), LDL-c = -8.0% (-10.4 --5.5)], the percent difference was greater among adults taking cholesterol medication [TC = -8.0% (-10.3 --5.7); LDL-c = -13.7% (-17.1 --10.2)] than adults not taking cholesterol medication [TC = -3.5% (-5.2 --1.6); LDL-c = -4.3% (-7.1 --1.5)] (interaction p-value: TC = <0.001; LDL-c = <0.001). From 2003-2012, mean TC and HDL-c significantly decreased among diabetic adults taking cholesterol medication [% difference per survey cycle (p-value for linear trend): TC = -2.3% (0.003) and HDL-c = -2.3% (0.033)]. Mean TC, HDL-c, and LDL-c levels did not significantly change from 2003 to 2012 in non-diabetic adults taking cholesterol medication or for adults not taking cholesterol medications. Diabetic adults were more likely to have lower lipid levels, except for triglyceride

Lecithin hydrophobicity modulates the process of cholesterol crystal nucleation and growth in supersaturated model bile systems.

OpenAIRE

Ochi, H; Tazuma, S; Kajiyama, G

1996-01-01

The present study was performed to determine whether the degree of lecithin hydrophobicity regulates bile metastability and, therefore, affects the process of cholesterol crystallization. Supersaturated model bile (MB) solutions were prepared with an identical composition on a molar basis (taurocholate/lecithin/cholesterol, 73:19.5:7.5; total lipid concentration 9 g/dl) except for the lecithin species; egg yolk phosphatidylcholine, soybean phosphatidylcholine, 1-palmitoyl-2-linoleoyl-sn-phosp...

Android and gynoid fat percentages and serum lipid levels in United States adults.

Science.gov (United States)

Min, Kyoung-Bok; Min, Jin-Young

2015-03-01

Accumulating evidence suggests that fat distribution is a better predictor of cardiovascular disease than body mass index (BMI). The aim of this study was to investigate the association of android and gynoid fat percentages with lipid profiles to determine whether android and/or gynoid fat percentages are associated with serum lipid levels. A population-based cross-sectional study. Five thousand six hundred and ninety-six adults (20 years and older) who participated in the National Health and Nutrition Examination Survey 2003-2006. The regional body composition in the android and gynoid regions was defined by dual energy X-ray absorptiometry (DXA). The estimation of lipid risk profiles included total cholesterol, high-density lipoprotein (HDL) -cholesterol, low-density lipoprotein (LDL) -cholesterol and triglycerides (TG). Regardless of gender, android and gynoid body fat percentages were positively and significantly correlated with BMI and waist circumference. After adjustment for age, ethnicity, education, smoking, alcohol consumption, dyslipidaemia and BMI, increases in android fat percentage were significantly associated with total cholesterol, TG and HDL cholesterol in males, and total cholesterol, HDL cholesterol and LDL cholesterol in females. The gynoid fat percentages showed a positive correlation with total cholesterol in males, whereas gynoid fat accumulation in females showed a favourable association with TG and HDL cholesterol. The observed associations differed according to ethnic groups. Our results suggest that regional fat distribution in the android and gynoid regions have different effects on lipid profiles, and that fat in the android region, rather than the gynoid region, may be an important factor in determining the risk of cardiovascular disease. © 2014 John Wiley & Sons Ltd.

Serum fatty acid composition in normal Japanese and its relationship with dietary fish and vegetable oil contents and blood lipid levels.

Science.gov (United States)

Nakamura, T; Takebe, K; Tando, Y; Arai, Y; Yamada, N; Ishii, M; Kikuchi, H; Machida, K; Imamura, K; Terada, A

1995-01-01

A survey was conducted on 110 normal Japanese adults (55 men and 55 women) to determine their caloric intake, dietary fat content and its origin (animal, plant, or marine). In addition, their blood lipid levels and fatty acid compositions were examined. Men in their 30s-50s consumed 2,600-2,800 calories and 60 g of fats, while women in the same age range consumed 2,000-2,200 calories and 52-58 g of fats. In both sexes, caloric, fat, and cholesterol intakes were lower for those in their 60s but protein and crude fiber consumption remained generally unchanged. When the dietary fats were classified according to origin, men and women in their 30s were found to consume less oil of marine origin. This appeared to be the result of a western style diet for Japanese adults in their 30s. Compared with men, women exhibited lower blood lipid levels. As age increased, the total cholesterol level of the blood rose in women. Thus the blood lipid level was generally equal in the two groups in their 60s. There was a positive correlation between the blood eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) levels and dietary consumption of fish oil. The marine/plant lipid ratio was positively correlated with the blood EPA/arachidonic acid ratio. Therefore, it was believed that the origin of the dietary fats consumed is a factor in determining the blood fatty acid profile. The linoleic acid (18:2), arachidonic acid (20:4), and 18:2 + 20:4 contents were negatively correlated to the total cholesterol level in the blood but positively correlated to the HDL-cholesterol level. Polyunsaturated fatty acids (18:2 + 20:4 + 20:5 + 22:6) were negatively correlated with the blood triglyceride level. From the findings presented above, we concluded that dietary fats not derived from animal sources should be classified into fish and vegetable oils to evaluate their dietary significance. We also noted that Japanese in their 30s consume less fish oil, indicating the western trend in their

Break the fast? Update on patient preparation for cholesterol testing.

Science.gov (United States)

Naugler, Christopher; Sidhu, Davinder

2014-10-01

To provide an update on the clinical usefulness of nonfasting versus fasting lipid testing to improve patient compliance, patient safety, and clinical assessment in cholesterol testing. Recommendations are identified as supported by good, fair, and poor (conflicting or insufficient) evidence, according to the classifications adopted by the Canadian Task Force on Preventive Health Care. Screening for dyslipidemia as a risk factor for coronary artery disease and management of lipid-lowering medications are key parts of primary care. Recent evidence has questioned the fasting requirement for lipid testing. In population-based studies, total cholesterol, high-density lipoprotein cholesterol, and non-low-density lipoprotein cholesterol all varied by an average of 2% with fasting status. For routine screening, nonfasting cholesterol measurement is now a reasonable alternative to a fasting cholesterol measurement. For patients with diabetes, the fasting requirement might be an important safety issue because of problems with hypoglycemia. For the monitoring of triglyceride and low-density lipoprotein cholesterol levels in patients taking lipid-lowering medications, fasting becomes more important. Fasting for routine lipid level determinations is largely unnecessary and unlikely to affect patient clinical risk stratification, while nonfasting measurement might improve patient compliance and safety. Copyright© the College of Family Physicians of Canada.

Cholesterol Induced Changes in the Characteristics of the Time Series From Planar Lipid Bilayer Membrane during Electroporation

International Nuclear Information System (INIS)

Kotulska, M.; Koronkiewicz, S.; Kalinowski, S.

2002-01-01

The electroporation can be used as a non-toxic method for introducing exogenous macromolecules, especially DNA and drugs, into various types of cells. Research in to new therapeutic methods based on Long Duration Electroporation (LDE) is of special interest. A new current-clamp method makes possible the electroporation of very long duration with no damage to bio-membranes. In this paper we compare responses of lipid planar bilayer membranes at physiological concentration of KCl, with lipid membranes formed at higher ionic strength, and membranes containing cholesterol. A longer lifespan of the membranes with cholesterol and membranes with increased ionic strength could be observed. Sensitivity of the power spectrum response to the presence of cholesterol, ionic strength, current intensity, and membrane ageing was examined. The membrane memory was analyzed by means of autocorrelation function and rescaled range analysis. We showed that the memory of the system decreases for higher current intensities and this relation is pronounced better at higher ionic strength. At low current intensities all membranes showed slightly persistent type of noise behavior with crossover to Brownian type of noise for higher current value. The transition w as much faster for higher ionic strength, where the next transition to anti-persistent response was observed for relatively low currents. Very interesting results were obtained from power spectrum analysis. At low current intensity, all membranes exhibited 1/f noise, which disappeared for higher currents, maintaining f β type with rising value of β. Membranes formed at lower ionic strength and with cholesterol showed a pronounced tendency to lose flicker noise while ageing, also with rising β value. (author)

Impacts of fat fromruminants’ meat on cardiovascular health and possible strategies to alter its lipid composition

DEFF Research Database (Denmark)

Vargas-Bello-Pérez, Einar; Larraín, Rafael E.

2017-01-01

intake of fat, saturated FAs and cholesterol as a means of reducing the risk of cardiovascular disease. Interestingly, ruminant meat has some bioactive lipids such as C18:1t11 and C18:2 c9, t11 which have been reported to have positive effects on human health. In order to improve muscle fat composition......In the last few decades there has been increased consumer interest in the fatty acid (FA) composition of ruminant meat due to its content of saturated FAs, which have been implicated in diseases associated with modern life. However, recent studies have questioned the recommendations to reduce...... from a human health standpoint, oilseeds, plant oils andmarine oils can be used in ruminant diets. On the other hand,molecular mechanisms play an important role in the alteration of the FA composition of muscle fat. Genetics offer a wide range of possibilities for improvement of muscle fat...

Blockade of oestrogen biosynthesis in peripubertal boys: effects on lipid metabolism, insulin sensitivity, and body composition.

Science.gov (United States)

Hero, Matti; Ankarberg-Lindgren, Carina; Taskinen, Marja-Riitta; Dunkel, Leo

2006-09-01

In males, the pubertal increase in sex hormone production has been associated with proatherogenic changes in lipid and carbohydrate metabolism. Aromatase inhibitors, a novel treatment modality for some growth disorders, may significantly influence these risk factors for cardiovascular disease by suppressing oestrogen biosynthesis and stimulating gonadal androgen production. In the current study, we explored the effects of aromatase inhibition on lipid metabolism, insulin sensitivity, body composition and serum adiponectin in peripubertal boys. Prospective, double-blind, randomised, placebo-controlled clinical study. Thirty-one boys, aged 9.0-14.5 years, with idiopathic short stature were treated with the aromatase inhibitor letrozole (2.5 mg/day) or placebo for 2 years. During the treatment, the concentrations of sex hormones, IGF-I, lipids, lipoproteins and adiponectin were followed-up. The percentage of fat mass (FM) was assessed by skinfold measurements and insulin resistance by homeostasis model assessment (HOMA) index. In pubertal boys, who received letrozole, high-density lipoprotein cholesterol (HDL-C) decreased by 0.47 mmol/l (P<0.01) during the study. Simultaneously, their percentage of FM decreased from 17.0 to 10.5 (P<0.001), in an inverse relationship with serum testosterone. The concentrations of low-density lipoprotein cholesterol, triglycerides and HOMA index remained at pretreatment level in both groups. Serum adiponectin decreased similarly in letrozole- and placebo-treated pubertal boys (2.9 and 3.3 mg/l respectively). In males, aromatase inhibition reduces HDL-C and decreases relative FM after the start of puberty. The treatment does not adversely affect insulin sensitivity in lean subjects.

Endogenous lipid (cholesterol) pneumonia in three captive Siberian tigers (Panthera tigris altaica).

Science.gov (United States)

Bollo, Enrico; Scaglione, Frine Eleonora; Chiappino, Laura; Sereno, Alessandra; Triberti, Orfeo; Schröder, Cathrin

2012-05-01

During the years 2009-2011, 7 Siberian tigers (Panthera tigris altaica), aged between 2 and 14 years, from the Safaripark of Pombia were referred for necropsy to the Department of Animal Pathology of the University of Turin (Italy). Three tigers, aged 10 (2 animals) and 14 years, had multifocal, irregularly distributed, white, soft, subpleural, 3-mm nodules scattered throughout the lungs. Histologically, there was a marked infiltration of macrophages, with foamy cytoplasm, and multinucleate giant cells interspersed with numerous clusters of cholesterol clefts. A mild lymphocytic infiltration was localized around the lesion. The findings were consistent with endogenous lipid pneumonia, which was considered an incidental finding of no clinical significance.

Easy, Fast, and Reproducible Quantification of Cholesterol and Other Lipids in Human Plasma by Combined High Resolution MSX and FTMS Analysis

Science.gov (United States)

Gallego, Sandra F.; Højlund, Kurt; Ejsing, Christer S.

2018-01-01

Reliable, cost-effective, and gold-standard absolute quantification of non-esterified cholesterol in human plasma is of paramount importance in clinical lipidomics and for the monitoring of metabolic health. Here, we compared the performance of three mass spectrometric approaches available for direct detection and quantification of cholesterol in extracts of human plasma. These approaches are high resolution full scan Fourier transform mass spectrometry (FTMS) analysis, parallel reaction monitoring (PRM), and novel multiplexed MS/MS (MSX) technology, where fragments from selected precursor ions are detected simultaneously. Evaluating the performance of these approaches in terms of dynamic quantification range, linearity, and analytical precision showed that the MSX-based approach is superior to that of the FTMS and PRM-based approaches. To further show the efficacy of this approach, we devised a simple routine for extensive plasma lipidome characterization using only 8 μL of plasma, using a new commercially available ready-to-spike-in mixture with 14 synthetic lipid standards, and executing a single 6 min sample injection with combined MSX analysis for cholesterol quantification and FTMS analysis for quantification of sterol esters, glycerolipids, glycerophospholipids, and sphingolipids. Using this simple routine afforded reproducible and absolute quantification of 200 lipid species encompassing 13 lipid classes in human plasma samples. Notably, the analysis time of this procedure can be shortened for high throughput-oriented clinical lipidomics studies or extended with more advanced MSALL technology (Almeida R. et al., J. Am. Soc. Mass Spectrom. 26, 133-148 [1]) to support in-depth structural elucidation of lipid molecules. [Figure not available: see fulltext.

Lipid composition of hepatic and adipose tissues from normal cats and from cats with idiopathic hepatic lipidosis.

Science.gov (United States)

Hall, J A; Barstad, L A; Connor, W E

1997-01-01

The purpose of this study was to characterize the lipid classes in hepatic and adipose tissues from cats with idiopathic hepatic lipidosis (IHL). Concentrations of triglyceride, phospholipid phosphorus, and free and total cholesterol were determined in lipid extracts of liver homogenates from 5 cats with IHL and 5 healthy control cats. Total fatty acid composition of liver and adipose tissue was also compared. Triglyceride accounted for 34% of liver by weight in cats with IHL (338 +/- 38 mg/g wet liver) versus 1% in control cats (9.9 +/- 1.0 mg/g wet liver, P hepatic tissue in the 2 groups differed; palmitate was higher (19.5 +/- 1.1% of total fatty acids in cats with IHL versus 9.2 +/- 2.7% in controls, P hepatic triglyceride in cats with IHL is the mobilization of fatty acids from adipose tissue.

Normal Non-HDL Cholesterol, Low Total Cholesterol, and HDL Cholesterol Levels in Sickle Cell Disease Patients in the Steady State: A Case-Control Study of Tema Metropolis.

Science.gov (United States)

Ephraim, Richard K D; Adu, Patrick; Ake, Edem; Agbodzakey, Hope; Adoba, Prince; Cudjoe, Obed; Agoni, Clement

2016-01-01

Background. Abnormal lipid homeostasis in sickle cell disease (SCD) is characterized by defects in plasma and erythrocyte lipids and may increase the risk of cardiovascular disease. This study assessed the lipid profile and non-HDL cholesterol level of SCD patients. Methods. A hospital-based cross-sectional study was conducted in 50 SCD patients, in the steady state, aged 8-28 years, attending the SCD clinic, and 50 healthy volunteers between the ages of 8-38 years. Serum lipids were determined by enzymatic methods and non-HDL cholesterol calculated by this formula: non-HDL-C = TC-HDL-C. Results. Total cholesterol (TC) ( p = 0.001) and high-density lipoprotein cholesterol (HDL-C) ( p < 0.0001) were significantly decreased in cases compared to controls. The levels of non-HDL-C, low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) were similar among the participants. The levels of decrease in TC and HDL were associated with whether a patient was SCD-SS or SCD-SC. Systolic blood pressure and diastolic blood pressure were each significantly associated with increased VLDL [SBP, p = 0.01, OR: 0.74 (CI: 0.6-0.93); DBP, p = 0.023, OR: 1.45 (CI: 1.05-2.0)]. Conclusion. Dyslipidemia is common among participants in this study. It was more pronounced in the SCD-SS than in SCD-SC. This dyslipidemia was associated with high VLDL as well as increased SBP and DBP.

Reversible mode of binding of serum proteins to DOTAP/cholesterol Lipoplexes: a possible explanation for intravenous lipofection efficiency.

Science.gov (United States)

Simberg, Dmitri; Weiss, Aryeh; Barenholz, Yechezkel

2005-09-01

There are many indications that interaction of serum proteins with intravenously injected cationic lipoplexes disturbs lipofection in vitro and in vivo. However, transfection with certain lipid compositions such as N-[1- (2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTAP)/cholesterol appears to be more resistant to serum and more efficacious. We investigated the mechanism of interaction between fluorescently labeled lipoplexes of the above composition and fluorescently labeled serum proteins. Fluorescence resonance energy transfer measurements in vitro indicate that serum proteins interact instantly and closely with the DOTAP/cholesterol lipoplexes. In accord with this, preinjection of fluorescently labeled serum into mice before injection of lipoplexes showed an immediate association of proteins with lipoplexes. Serum proteins colocalized with the lipoplexes in the lung vasculature; however, they dissociated from the cationic lipid as soon as 1 hr postinjection, probably because of displacement of serum proteins from lipoplexes by extracellular proteoglycans. Indeed, this displacement was imitated by heparin, a typical glycosaminoglycan, and could be explained by the inability of weakly acidic serum proteins to neutralize the DOTAP/cholesterol electrical surface potential psi0. The stability of the cationic lipid psi0 in serum could be a key reason for the high lung association and transfection efficiency with this formulation.

Nanomolar Cellular Antisense Activity of Peptide Nucleic Acid (PNA) Cholic Acid ("Umbrella") and Cholesterol Conjugates Delivered by Cationic Lipids

DEFF Research Database (Denmark)

Shiraishi, Takehiko; Nielsen, Peter E

2012-01-01

of cholesterol and cholic acid ("umbrella") derivatives of splice correction antisense PNA oligomers. While the conjugates alone were practically inactive up to 1 µM, their activity was dramatically improved when delivered by a cationic lipid transfection agent (LipofectAMINE2000). In particular, PNAs...

Biochemical and Bioimaging Evidence of Cholesterol in Acquired Cholesteatoma

DEFF Research Database (Denmark)

Thorsted, Bjarne; Bloksgaard, Maria; Groza, Alexandra

2016-01-01

: The results show that the total lipid content of the cholesteatoma matrix is similar to that of stratum corneum from skin and that the cholesteatoma matrix unquestionably contains cholesterol. The cholesterol content in the cholesteatoma matrix is increased by over 30% (w/w dry weight) compared to the control....... The cholesterol sulfate content is below 1% of the total lipids in both the cholesteatoma and the control. Cholesterol ester was reduced by over 30% when compared to the control. CONCLUSIONS: The content of cholesterol in the cholesteatoma matrix is significantly different from that in stratum corneum from skin...

Achieving secondary prevention low-density lipoprotein particle concentration goals using lipoprotein cholesterol-based data.

Directory of Open Access Journals (Sweden)

Simon C Mathews

Full Text Available BACKGROUND: Epidemiologic studies suggest that LDL particle concentration (LDL-P may remain elevated at guideline recommended LDL cholesterol goals, representing a source of residual risk. We examined the following seven separate lipid parameters in achieving the LDL-P goal of <1000 nmol/L goal for very high risk secondary prevention: total cholesterol to HDL cholesterol ratio, TC/HDL, <3; a composite of ATP-III very high risk targets, LDL-C<70 mg/dL, non-HDL-C<100 mg/dL and TG<150 mg/dL; a composite of standard secondary risk targets, LDL-C<100, non-HDL-C<130, TG<150; LDL phenotype; HDL-C ≥ 40; TG<150; and TG/HDL-C<3. METHODS: We measured ApoB, ApoAI, ultracentrifugation lipoprotein cholesterol and NMR lipoprotein particle concentration in 148 unselected primary and secondary prevention patients. RESULTS: TC/HDL-C<3 effectively discriminated subjects by LDL-P goal (F = 84.1, p<10(-6. The ATP-III very high risk composite target (LDL-C<70, nonHDL-C<100, TG<150 was also effective (F = 42.8, p<10(-5. However, the standard secondary prevention composite (LDL-C<100, non-HDL-C<130, TG<150 was also effective but yielded higher LDL-P than the very high risk composite (F = 42.0, p<10(-5 with upper 95% confidence interval of LDL-P less than 1000 nmol/L. TG<150 and TG/HDL-C<3 cutpoints both significantly discriminated subjects but the LDL-P upper 95% confidence intervals fell above goal of 1000 nmol/L (F = 15.8, p = 0.0001 and F = 9.7, p = 0.002 respectively. LDL density phenotype neared significance (F = 2.85, p = 0.094 and the HDL-C cutpoint of 40 mg/dL did not discriminate (F = 0.53, p = 0.47 alone or add discriminatory power to ATP-III targets. CONCLUSIONS: A simple composite of ATP-III very high risk lipoprotein cholesterol based treatment targets or TC/HDL-C ratio <3 most effectively identified subjects meeting the secondary prevention target level of LDL-P<1000 nmol/L, providing a potential alternative to advanced lipid testing in many clinical

Lipid alterations in lipid rafts from Alzheimer's disease human brain cortex.

Science.gov (United States)

Martín, Virginia; Fabelo, Noemí; Santpere, Gabriel; Puig, Berta; Marín, Raquel; Ferrer, Isidre; Díaz, Mario

2010-01-01

Lipid rafts are membrane microdomains intimately associated with cell signaling. These biochemical microstructures are characterized by their high contents of sphingolipids, cholesterol and saturated fatty acids and a reduced content of polyunsaturated fatty acids (PUFA). Here, we have purified lipid rafts of human frontal brain cortex from normal and Alzheimer's disease (AD) and characterized their biochemical lipid composition. The results revealed that lipid rafts from AD brains exhibit aberrant lipid profiles compared to healthy brains. In particular, lipid rafts from AD brains displayed abnormally low levels of n-3 long chain polyunsaturated fatty acids (LCPUFA, mainly 22:6n-3, docosahexaenoic acid) and monoenes (mainly 18:1n-9, oleic acid), as well as reduced unsaturation and peroxidability indexes. Also, multiple relationships between phospholipids and fatty acids were altered in AD lipid rafts. Importantly, no changes were observed in the mole percentage of lipid classes and fatty acids in rafts from normal brains throughout the lifespan (24-85 years). These indications point to the existence of homeostatic mechanisms preserving lipid raft status in normal frontal cortex. The disruption of such mechanisms in AD brains leads to a considerable increase in lipid raft order and viscosity, which may explain the alterations in lipid raft signaling observed in AD.

Effects of apolipoproteins on the kinetics of cholesterol exchange

International Nuclear Information System (INIS)

Letizia, J.Y.; Phillips, M.C.

1991-01-01

The effects of apolipoproteins on the kinetics of cholesterol exchange have been investigated by monitoring the transfer of [ 14 C]cholesterol from donor phospholipid/cholesterol complexes containing human apolipoproteins A, B, or C. Negatively charged discoidal and vesicular particles containing purified apolipoproteins complexed with lipid and a trace of [ 14 C]cholesterol were incubated with a 10-fold excess of neutral, acceptor, small unilamellar vesicles. The donor and acceptor particles were separated by chromatogrphy of DEAE-Sepharose, and the rate of movement of labeled cholesterol was analyzed as a first-order exchange process. The kinetics of exchange of cholesterol from both vesicular and discoidal complexes that contain apoproteins are consistent with an aqueous diffusion mechanism, as has been established previously for PC/cholesterol SUV. Apolipoproteins A-I, A-II, reduced and carboxymethylated A-11, and B-100 present in SUV at the same lipid/protein (w/w) ratio all enhance the rate of cholesterol exchange to about the same degree. Cholesterol molecules exchange more rapidly from discoidal complexes. Generally, as the diameter of apoprotein/phospholipid/cholesterol discs decreases, t 1/2 for cholesterol exchange decreases. Since small bilayer discs have a relatively high ratio of boundary to face surface area, cholesterol molecules desorb more rapidly than from larger discs. The modulation of lipid packing by the apoprotein molecules present at the surface of lipoprotein particles affects the rate of cholesterol exchange from such particles

RaftProt: mammalian lipid raft proteome database.

Science.gov (United States)

Shah, Anup; Chen, David; Boda, Akash R; Foster, Leonard J; Davis, Melissa J; Hill, Michelle M

2015-01-01

RaftProt (http://lipid-raft-database.di.uq.edu.au/) is a database of mammalian lipid raft-associated proteins as reported in high-throughput mass spectrometry studies. Lipid rafts are specialized membrane microdomains enriched in cholesterol and sphingolipids thought to act as dynamic signalling and sorting platforms. Given their fundamental roles in cellular regulation, there is a plethora of information on the size, composition and regulation of these membrane microdomains, including a large number of proteomics studies. To facilitate the mining and analysis of published lipid raft proteomics studies, we have developed a searchable database RaftProt. In addition to browsing the studies, performing basic queries by protein and gene names, searching experiments by cell, tissue and organisms; we have implemented several advanced features to facilitate data mining. To address the issue of potential bias due to biochemical preparation procedures used, we have captured the lipid raft preparation methods and implemented advanced search option for methodology and sample treatment conditions, such as cholesterol depletion. Furthermore, we have identified a list of high confidence proteins, and enabled searching only from this list of likely bona fide lipid raft proteins. Given the apparent biological importance of lipid raft and their associated proteins, this database would constitute a key resource for the scientific community. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Impact of Dietary Cholesterol on the Pathophysiology of Infectious and Autoimmune Disease

Directory of Open Access Journals (Sweden)

Catherine J. Andersen

2018-06-01

Full Text Available Cellular cholesterol metabolism, lipid raft formation, and lipoprotein interactions contribute to the regulation of immune-mediated inflammation and response to pathogens. Lipid pathways have been implicated in the pathogenesis of bacterial and viral infections, whereas altered lipid metabolism may contribute to immune dysfunction in autoimmune diseases, such as systemic lupus erythematosus, multiple sclerosis, and rheumatoid arthritis. Interestingly, dietary cholesterol may exert protective or detrimental effects on risk, progression, and treatment of different infectious and autoimmune diseases, although current findings suggest that these effects are variable across populations and different diseases. Research evaluating the effects of dietary cholesterol, often provided by eggs or as a component of Western-style diets, demonstrates that cholesterol-rich dietary patterns affect markers of immune inflammation and cellular cholesterol metabolism, while additionally modulating lipoprotein profiles and functional properties of HDL. Further, cholesterol-rich diets appear to differentially impact immunomodulatory lipid pathways across human populations of variable metabolic status, suggesting that these complex mechanisms may underlie the relationship between dietary cholesterol and immunity. Given the Dietary Guidelines for Americans 2015–2020 revision to no longer include limitations on dietary cholesterol, evaluation of dietary cholesterol recommendations beyond the context of cardiovascular disease risk is particularly timely. This review provides a comprehensive and comparative analysis of significant and controversial studies on the role of dietary cholesterol and lipid metabolism in the pathophysiology of infectious disease and autoimmune disorders, highlighting the need for further investigation in this developing area of research.

Lipid and lipoprotein abnormalities in acute lymphoblastic leukemia survivors.

Science.gov (United States)

Morel, Sophia; Leahy, Jade; Fournier, Maryse; Lamarche, Benoit; Garofalo, Carole; Grimard, Guy; Poulain, Floriane; Delvin, Edgard; Laverdière, Caroline; Krajinovic, Maja; Drouin, Simon; Sinnett, Daniel; Marcil, Valérie; Levy, Emile

2017-05-01

Survivors of acute lymphoblastic leukemia (ALL), the most common cancer in children, are at increased risk of developing late cardiometabolic conditions. However, the mechanisms are not fully understood. This study aimed to characterize the plasma lipid profile, Apo distribution, and lipoprotein composition of 80 childhood ALL survivors compared with 22 healthy controls. Our results show that, despite their young age, 50% of the ALL survivors displayed dyslipidemia, characterized by increased plasma triglyceride (TG) and LDL-cholesterol, as well as decreased HDL-cholesterol. ALL survivors exhibited lower plasma Apo A-I and higher Apo B-100 and C-II levels, along with elevated Apo C-II/C-III and B-100/A-I ratios. VLDL fractions of dyslipidemic ALL survivors contained more TG, free cholesterol, and phospholipid moieties, but less protein. Differences in Apo content were found between ALL survivors and controls for all lipoprotein fractions except HDL 3 HDL 2 , especially, showed reduced Apo A-I and raised Apo A-II, leading to a depressed Apo A-I/A-II ratio. Analysis of VLDL-Apo Cs disclosed a trend for higher Apo C-III 1 content in dyslipidemic ALL survivors. In conclusion, this thorough investigation demonstrates a high prevalence of dyslipidemia in ALL survivors, while highlighting significant abnormalities in their plasma lipid profile and lipoprotein composition. Special attention must, therefore, be paid to these subjects given the atherosclerotic potency of lipid and lipoprotein disorders. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

Ordering effects of cholesterol and its analogues

DEFF Research Database (Denmark)

Róg, Tomasz; Pasenkiewicz-Gierula, Marta; Vattulainen, Ilpo

2009-01-01

Without any exaggeration, cholesterol is one of the most important lipid species in eukaryotic cells. Its effects on cellular membranes and functions range from purely mechanistic to complex metabolic ones, besides which it is also a precursor of the sex hormones (steroids) and several vitamins....... In this review, we discuss the biophysical effects of cholesterol on the lipid bilayer, in particular the ordering and condensing effects, concentrating on the molecular level or inter-atomic interactions perspective, starting from two-component systems and proceeding to many-component ones e.g., modeling lipid...... rafts. Particular attention is paid to the roles of the methyl groups in the cholesterol ring system, and their possible biological function. Although our main research methodology is computer modeling, in this review we make extensive comparisons between experiments and different modeling approaches....

Cholesterol Depletion from a Ceramide/Cholesterol Mixed Monolayer: A Brewster Angle Microscope Study

KAUST Repository

Mandal, Pritam

2016-06-01

Cholesterol is crucial to the mechanical properties of cell membranes that are important to cells’ behavior. Its depletion from the cell membranes could be dramatic. Among cyclodextrins (CDs), methyl beta cyclodextrin (MβCD) is the most efficient to deplete cholesterol (Chol) from biomembranes. Here, we focus on the depletion of cholesterol from a C16 ceramide/cholesterol (C16-Cer/Chol) mixed monolayer using MβCD. While the removal of cholesterol by MβCD depends on the cholesterol concentration in most mixed lipid monolayers, it does not depend very much on the concentration of cholesterol in C16-Cer/Chol monolayers. The surface pressure decay during depletion were described by a stretched exponential that suggested that the cholesterol molecules are unable to diffuse laterally and behave like static traps for the MβCD molecules. Cholesterol depletion causes morphology changes of domains but these disrupted monolayers domains seem to reform even when cholesterol level was low.

21-Methylpyrenyl-cholesterol stably and specifically associates with lipoprotein peripheral hemi-membrane: A new labelling tool

Energy Technology Data Exchange (ETDEWEB)

Gaibelet, Gérald [INSERM U563, CHU Purpan, Toulouse (France); CEA, SB2SM and UMR8221 CNRS, IBiTec-Saclay, Gif-sur-Yvette (France); Tercé, François [Université Toulouse III, UMR 1048, Toulouse (France); INSERM U1048, Toulouse (France); Bertrand-Michel, Justine [Université Toulouse III, UMR 1048, Toulouse (France); INSERM U1048, Lipidomic Platform Metatoul, Toulouse (France); Allart, Sophie [Plateau Technique d’Imagerie Cellulaire, INSERM U1043, Toulouse (France); Azalbert, Vincent [Université Toulouse III, UMR 1048, Toulouse (France); INSERM U1048, Toulouse (France); Lecompte, Marie-France [INSERM U563, Faculté de Médecine de Rangueil, Toulouse (France); Collet, Xavier [Université Toulouse III, UMR 1048, Toulouse (France); INSERM U1048, Toulouse (France); Orlowski, Stéphane, E-mail: stephane.orlowski@cea.fr [INSERM U563, CHU Purpan, Toulouse (France); CEA, SB2SM and UMR8221 CNRS, IBiTec-Saclay, Gif-sur-Yvette (France)

2013-11-01

Highlights: •21-Methylpyrenyl-cholesterol specifically and stably associates to lipoproteins. •It is not esterified by LCAT, and thus reliably labels their peripheral hemi-membrane. •HDL vs. LDL are well distinguishable by various fluorescent labelling characteristics. •LDL peripheral hemi-membrane harbors cholesterol-rich ordered lipid (micro)domains. •Cultured cells can be stained by such labelled lipoproteins-mediated delivery. -- Abstract: Lipoproteins are important biological components. However, they have few convenient fluorescent labelling probes currently reported, and their physiological reliability can be questioned. We compared the association of two fluorescent cholesterol derivatives, 22-nitrobenzoxadiazole-cholesterol (NBD-Chol) and 21-methylpyrenyl-cholesterol (Pyr-met-Chol), to serum lipoproteins and to purified HDL and LDL. Both lipoproteins could be stably labelled by Pyr-met-Chol, but virtually not by NBD-Chol. At variance with NBD-Chol, LCAT did not esterify Pyr-met-Chol. The labelling characteristics of lipoproteins by Pyr-met-Chol were well distinguishable between HDL and LDL, regarding dializability, associated probe amount and labelling kinetics. We took benefit of the pyrene labelling to approach the structural organization of LDL peripheral hemi-membrane, since Pyr-met-Chol-labelled LDL, but not HDL, presented a fluorescence emission of pyrene excimers, indicating that the probe was present in an ordered lipid micro-environment. Since the peripheral membrane of LDL contains more sphingomyelin (SM) than HDL, this excimer formation was consistent with the existence of cholesterol- and SM-enriched lipid microdomains in LDL, as already suggested in model membranes of similar composition and reminiscent to the well-described “lipid rafts” in bilayer membranes. Finally, we showed that Pyr-met-Chol could stain cultured PC-3 cells via lipoprotein-mediated delivery, with a staining pattern well different to that observed with NBD

21-Methylpyrenyl-cholesterol stably and specifically associates with lipoprotein peripheral hemi-membrane: A new labelling tool

International Nuclear Information System (INIS)

Gaibelet, Gérald; Tercé, François; Bertrand-Michel, Justine; Allart, Sophie; Azalbert, Vincent; Lecompte, Marie-France; Collet, Xavier; Orlowski, Stéphane

2013-01-01

Highlights: •21-Methylpyrenyl-cholesterol specifically and stably associates to lipoproteins. •It is not esterified by LCAT, and thus reliably labels their peripheral hemi-membrane. •HDL vs. LDL are well distinguishable by various fluorescent labelling characteristics. •LDL peripheral hemi-membrane harbors cholesterol-rich ordered lipid (micro)domains. •Cultured cells can be stained by such labelled lipoproteins-mediated delivery. -- Abstract: Lipoproteins are important biological components. However, they have few convenient fluorescent labelling probes currently reported, and their physiological reliability can be questioned. We compared the association of two fluorescent cholesterol derivatives, 22-nitrobenzoxadiazole-cholesterol (NBD-Chol) and 21-methylpyrenyl-cholesterol (Pyr-met-Chol), to serum lipoproteins and to purified HDL and LDL. Both lipoproteins could be stably labelled by Pyr-met-Chol, but virtually not by NBD-Chol. At variance with NBD-Chol, LCAT did not esterify Pyr-met-Chol. The labelling characteristics of lipoproteins by Pyr-met-Chol were well distinguishable between HDL and LDL, regarding dializability, associated probe amount and labelling kinetics. We took benefit of the pyrene labelling to approach the structural organization of LDL peripheral hemi-membrane, since Pyr-met-Chol-labelled LDL, but not HDL, presented a fluorescence emission of pyrene excimers, indicating that the probe was present in an ordered lipid micro-environment. Since the peripheral membrane of LDL contains more sphingomyelin (SM) than HDL, this excimer formation was consistent with the existence of cholesterol- and SM-enriched lipid microdomains in LDL, as already suggested in model membranes of similar composition and reminiscent to the well-described “lipid rafts” in bilayer membranes. Finally, we showed that Pyr-met-Chol could stain cultured PC-3 cells via lipoprotein-mediated delivery, with a staining pattern well different to that observed with NBD

Functional genomics reveals increases in cholesterol biosynthetic genes and highly unsaturated fatty acid biosynthesis after dietary substitution of fish oil with vegetable oils in Atlantic salmon (Salmo salar

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Bron James E

2008-06-01

Full Text Available Abstract Background There is an increasing drive to replace fish oil (FO in finfish aquaculture diets with vegetable oils (VO, driven by the short supply of FO derived from wild fish stocks. However, little is known of the consequences for fish health after such substitution. The effect of dietary VO on hepatic gene expression, lipid composition and growth was determined in Atlantic salmon (Salmo salar, using a combination of cDNA microarray, lipid, and biochemical analysis. FO was replaced with VO, added to diets as rapeseed (RO, soybean (SO or linseed (LO oils. Results Dietary VO had no major effect on growth of the fish, but increased the whole fish protein contents and tended to decrease whole fish lipid content, thus increasing the protein:lipid ratio. Expression levels of genes of the highly unsaturated fatty acid (HUFA and cholesterol biosynthetic pathways were increased in all vegetable oil diets as was SREBP2, a master transcriptional regulator of these pathways. Other genes whose expression was increased by feeding VO included those of NADPH generation, lipid transport, peroxisomal fatty acid oxidation, a marker of intracellular lipid accumulation, and protein and RNA processing. Consistent with these results, HUFA biosynthesis, hepatic β-oxidation activity and enzymic NADPH production were changed by VO, and there was a trend for increased hepatic lipid in LO and SO diets. Tissue cholesterol levels in VO fed fish were the same as animals fed FO, whereas fatty acid composition of the tissues largely reflected those of the diets and was marked by enrichment of 18 carbon fatty acids and reductions in 20 and 22 carbon HUFA. Conclusion This combined gene expression, compositional and metabolic study demonstrates that major lipid metabolic effects occur after replacing FO with VO in salmon diets. These effects are most likely mediated by SREBP2, which responds to reductions in dietary cholesterol. These changes are sufficient to maintain

Radiation-induced lipid peroxidation: influence of oxygen concentration and membrane lipid composition

International Nuclear Information System (INIS)

Wolters, H.; Tilburg, C.A.M. van; Konings, A.W.T.

1987-01-01

Radiation -induced lipid peroxidation phospholipid liposomes was investigated in terms of its dependence on lipid composition and oxygen concentration. Non-peroxidizable lipid incorporated in the liposomes reduced the rate of peroxidation of the peroxidizable phospholipid acyl chains, possibly by restricting the length of chain reactions. The latter effect is believed to be caused by interference of the non-peroxidizable lipids in the bilayer. At low oxygen concentration lipid peroxidation was reduced. The cause of this limited peroxidation may be a reduced number of radical initiation reactions possibly involving oxygen-derived superoxide radicals. Killing of proliferating mammalian cells, irradiated at oxygen concentrations ranging from 0 to 100%, appeared to be independent of the concentration of peroxidizable phospholipids in the cell membranes. This indicates that lipid peroxidation is not the determining process in radiation-induced reproductive cell death. (author)

Zebrafish Embryonic Lipidomic Analysis Reveals that the Yolk Cell Is Metabolically Active in Processing Lipid

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Daniel Fraher

2016-02-01

Full Text Available The role of lipids in providing energy and structural cellular components during vertebrate development is poorly understood. To elucidate these roles further, we visualized lipid deposition and examined expression of key lipid-regulating genes during zebrafish embryogenesis. We also conducted a semiquantitative analysis of lipidomic composition using liquid chromatography (LC-mass spectrometry. Finally, we analyzed processing of boron-dipyrromethene (BODIPY lipid analogs injected into the yolk using thin layer chromatography. Our data reveal that the most abundant lipids in the embryo are cholesterol, phosphatidylcholine, and triglyceride. Moreover, we demonstrate that lipids are processed within the yolk prior to mobilization to the embryonic body. Our data identify a metabolically active yolk and body resulting in a dynamic lipid composition. This provides a foundation for studying lipid biology during normal or pharmacologically compromised embryogenesis.

Generalized Anxiety Disorder (GAD) and Comorbid Major Depression with GAD Are Characterized by Enhanced Nitro-oxidative Stress, Increased Lipid Peroxidation, and Lowered Lipid-Associated Antioxidant Defenses.

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Maes, Michael; Bonifacio, Kamila Landucci; Morelli, Nayara Rampazzo; Vargas, Heber Odebrecht; Moreira, Estefânia Gastaldello; St Stoyanov, Drozdstoy; Barbosa, Décio Sabbatini; Carvalho, André F; Nunes, Sandra Odebrecht Vargas

2018-05-07

Accumulating evidence shows that nitro-oxidative pathways play an important role in the pathophysiology of major depressive disorder (MDD) and bipolar disorder (BD) and maybe anxiety disorders. The current study aims to examine superoxide dismutase (SOD1), catalase, lipid hydroperoxides (LOOH), nitric oxide metabolites (NOx), advanced oxidation protein products (AOPP), malondialdehyde (MDA), glutathione (GSH), paraoxonase 1 (PON1), high-density lipoprotein cholesterol (HDL), and uric acid (UA) in participants with and without generalized anxiety disorder (GAD) co-occurring or not with BD, MDD, or tobacco use disorder. Z unit-weighted composite scores were computed as indices of nitro-oxidative stress driving lipid and protein oxidation. SOD1, LOOH, NOx, and uric acid were significantly higher and HDL and PON1 significantly lower in participants with GAD than in those without GAD. GAD was more adequately predicted by increased SOD + LOOH + NOx and lowered HDL + PON1 composite scores. Composite scores of nitro-oxidative stress coupled with aldehyde and AOPP production were significantly increased in participants with comorbid GAD + MDD as compared with all other study groups, namely MDD, GAD + BD, BD, GAD, and healthy controls. In conclusion, GAD is characterized by increased nitro-oxidative stress and lipid peroxidation and lowered lipid-associated antioxidant defenses, while increased uric acid levels in GAD may protect against aldehyde production and protein oxidation. This study suggests that increased nitro-oxidative stress and especially increased SOD1 activity, NO production, and lipid peroxidation as well as lowered HDL-cholesterol and PON1 activity could be novel drug targets for GAD especially when comorbid with MDD.

Corn oil improves the plasma lipoprotein lipid profile compared with extra-virgin olive oil consumption in men and women with elevated cholesterol: results from a randomized controlled feeding trial.

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Maki, Kevin C; Lawless, Andrea L; Kelley, Kathleen M; Kaden, Valerie N; Geiger, Constance J; Dicklin, Mary R

2015-01-01

Restricted intakes of saturated and trans-fatty acids is emphasized in heart-healthy diets, and replacement with poly- and monounsaturated fatty acids is encouraged. To compare the effects of polyunsaturated fatty acid-rich corn oil (CO) and monounsaturated fatty acid-rich extra-virgin olive oil (EVOO) on plasma lipids in men and women (N = 54) with fasting low-density lipoprotein cholesterol (LDL-C) ≥130 mg/dL and consumption away from the clinic. Baseline mean (standard error) lipids in mg/dL were: LDL-C 153.3 (3.5), total cholesterol (total-C) 225.7 (3.9), non-high-density lipoprotein (non-HDL)-C 178.3 (3.7), HDL-C 47.4 (1.7), total-C/HDL-C 5.0 (0.2), and TG 124.8 (7.2). CO resulted in significantly larger least-squares mean % changes (all P Consumption of CO in a weight-maintenance, low saturated fat and cholesterol diet resulted in more favorable changes in LDL-C and other atherogenic lipids vs EVOO. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Effects of Dietary Coconut Oil as a Medium-chain Fatty Acid Source on Performance, Carcass Composition and Serum Lipids in Male Broilers.

Science.gov (United States)

Wang, Jianhong; Wang, Xiaoxiao; Li, Juntao; Chen, Yiqiang; Yang, Wenjun; Zhang, Liying

2015-02-01

This study was conducted to investigate the effects of dietary coconut oil as a medium-chain fatty acid (MCFA) source on performance, carcass composition and serum lipids in male broilers. A total of 540, one-day-old, male Arbor Acres broilers were randomly allotted to 1 of 5 treatments with each treatment being applied to 6 replicates of 18 chicks. The basal diet (i.e., R0) was based on corn and soybean meal and was supplemented with 1.5% soybean oil during the starter phase (d 0 to 21) and 3.0% soybean oil during the grower phase (d 22 to 42). Four experimental diets were formulated by replacing 25%, 50%, 75%, or 100% of the soybean oil with coconut oil (i.e., R25, R50, R75, and R100). Soybean oil and coconut oil were used as sources of long-chain fatty acid and MCFA, respectively. The feeding trial showed that dietary coconut oil had no effect on weight gain, feed intake or feed conversion. On d 42, serum levels of total cholesterol, low-density lipoprotein cholesterol, and low-density lipoprotein/high-density lipoprotein cholesterol were linearly decreased as the coconut oil level increased (pcoconut oil level increased (poil in diets with coconut oil is the optimum level to reduce fat deposition and favorably affect lipid profiles without impairing performance in broilers.

Central Nervous System Demyelination and Remyelination is Independent from Systemic Cholesterol Level in Theiler's Murine Encephalomyelitis.

Science.gov (United States)

Raddatz, Barbara B; Sun, Wenhui; Brogden, Graham; Sun, Yanyong; Kammeyer, Patricia; Kalkuhl, Arno; Colbatzky, Florian; Deschl, Ulrich; Naim, Hassan Y; Baumgärtner, Wolfgang; Ulrich, Reiner

2016-01-01

High dietary fat and/or cholesterol intake is a risk factor for multiple diseases and has been debated for multiple sclerosis. However, cholesterol biosynthesis is a key pathway during myelination and disturbances are described in demyelinating diseases. To address the possible interaction of dyslipidemia and demyelination, cholesterol biosynthesis gene expression, composition of the body's major lipid repositories and Paigen diet-induced, systemic hypercholesterolemia were examined in Theiler's murine encephalomyelitis (TME) using histology, immunohistochemistry, serum clinical chemistry, microarrays and high-performance thin layer chromatography. TME-virus (TMEV)-infected mice showed progressive loss of motor performance and demyelinating leukomyelitis. Gene expression associated with cholesterol biosynthesis was overall down-regulated in the spinal cord of TMEV-infected animals. Spinal cord levels of galactocerebroside and sphingomyelin were reduced on day 196 post TMEV infection. Paigen diet induced serum hypercholesterolemia and hepatic lipidosis. However, high dietary fat and cholesterol intake led to no significant differences in clinical course, inflammatory response, astrocytosis, and the amount of demyelination and remyelination in the spinal cord of TMEV-infected animals. The results suggest that down-regulation of cholesterol biosynthesis is a transcriptional marker for demyelination, quantitative loss of myelin-specific lipids, but not cholesterol occurs late in chronic demyelination, and serum hypercholesterolemia exhibited no significant effect on TMEV infection. © 2015 International Society of Neuropathology.

Accumulation of raft lipids in T-cell plasma membrane domains engaged in TCR signalling

DEFF Research Database (Denmark)

Zech, Tobias; Ejsing, Christer S.; Gaus, Katharina

2009-01-01

Activating stimuli for T lymphocytes are transmitted through plasma membrane domains that form at T-cell antigen receptor (TCR) signalling foci. Here, we determined the molecular lipid composition of immunoisolated TCR activation domains. We observed that they accumulate cholesterol, sphingomyelin...... and saturated phosphatidylcholine species as compared with control plasma membrane fragments. This provides, for the first time, direct evidence that TCR activation domains comprise a distinct molecular lipid composition reminiscent of liquid-ordered raft phases in model membranes. Interestingly, TCR activation...... domains were also enriched in plasmenyl phosphatidylethanolamine and phosphatidylserine. Modulating the T-cell lipidome with polyunsaturated fatty acids impaired the plasma membrane condensation at TCR signalling foci and resulted in a perturbed molecular lipid composition. These results correlate...

Scavenger receptor class B member 1 protein: hepatic regulation and its effects on lipids, reverse cholesterol transport, and atherosclerosis

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Kent AP

2011-04-01

Full Text Available Anthony P Kent, Ioannis M StylianouDepartment of Medicine and Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA, USAAbstract: Scavenger receptor class B member 1 (SR-BI, also known as SCARB1 is the primary receptor for the selective uptake of cholesterol from high-density lipoprotein (HDL. SR-BI is present in several key tissues; however, its presence and function in the liver is deemed the most relevant for protection against atherosclerosis. Cholesterol is transferred from HDL via SR-BI to the liver, which ultimately results in the excretion of cholesterol via bile and feces in what is known as the reverse cholesterol transport pathway. Much of our knowledge of SR-BI hepatic function and regulation is derived from mouse models and in vitro characterization. Multiple independent regulatory mechanisms of SR-BI have been discovered that operate at the transcriptional and post-transcriptional levels. In this review we summarize the critical discoveries relating to hepatic SR-BI cholesterol metabolism, atherosclerosis, and regulation of SR-BI, as well as alternative functions that may indirectly affect atherosclerosis.Keywords: SR-BI, SCARB1, lipids, atherosclerosis, CAD, mouse models

Dairy products and plasma cholesterol levels

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Lena Ohlsson

2010-08-01

Full Text Available Cholesterol synthesized in the body or ingested is an essential lipid component for human survival from our earliest life. Newborns ingest about 3–4 times the amount per body weight through mother's milk compared to the dietary intake of adults. A birth level of 1.7 mmol/L plasma total cholesterol will increase to 4–4.5 mmol/L during the nursing period and continue to increase from adulthood around 40% throughout life. Coronary artery disease and other metabolic disorders are strongly associated with low-density lipoprotein (LDL and high-density lipoprotein (HDL cholesterol as well as triacylglycerol concentration. Milk fat contains a broad range of fatty acids and some have a negative impact on the cholesterol rich lipoproteins. The saturated fatty acids (SFAs, such as palmitic acid (C16:0, myristic acid (C14:0, and lauric acid (C12:0, increase total plasma cholesterol, especially LDL, and constitute 11.3 g/L of bovine milk, which is 44.8% of total fatty acid in milk fat. Replacement of dairy SFA and trans-fatty acids with polyunsaturated fatty acids decreases plasma cholesterol, especially LDL cholesterol, and is associated with a reduced risk of cardiovascular disease. Available data shows different effects on lipoproteins for different dairy products and there is uncertainty as to the impact a reasonable intake amount of dairy items has on cardiovascular risk. The aim of this review is to elucidate the effect of milk components and dairy products on total cholesterol, LDL, HDL, and the LDL/HDL quotients. Based on eight recent randomized controlled trials of parallel or cross-over design and recent reviews it can be concluded that replacement of saturated fat mainly (but not exclusively derived from high-fat dairy products with low-fat dairy products lowers LDL/HDL cholesterol and total/HDL cholesterol ratios. Whey, dairy fractions enriched in polar lipids, and techniques such as fermentation, or fortification of cows feeding can be used

Low HDL cholesterol is correlated to the acute ischemic stroke with diabetes mellitus.

Science.gov (United States)

Luo, Yun; Li, Jingwei; Zhang, Junfeng; Xu, Yun

2014-11-14

To clarify the role of lipid composition in the occurrence of acute ischemic stroke (AIS) with diabetes mellitus (DM) and its influence factors. Data was collected from the patients hospitalization in Affiliated Drum Tower Hospital of Nanjing University Medical School from October 2008 to May 2012, which included AIS and non-AIS consist of transient ischemic attack (TIA) and Vertigo or dizzy. Lipid and other risk factors including blood glucose (BG), uric acid (UA), hypertension, DM and atrial fibrillation (AF) were investigated in relation to occurrence of AIS. The level of high density lipoprotein (HDL) cholesterol was decreased obviously in the DM group compared to the non-DM group and low level of HDL cholesterol was prevalent in the AIS patients with DM. logistic regression demonstrated that decreased HDL cholesterol was correlated to the AIS with DM, not all AIS, and the relative risk of ischemic stroke in low HDL cholesterol level group was 2.113 (95% CI = 1.191-3.749, P = 0.011) compared to the high level group. Furthermore, age has the obviously impact on it. HDL cholesterol was correlated to the AIS with DM just in the populations of aged ≦70 years (OR = 0.192, P = 0.000), low level of HDL cholesterol had more high risk of ischemic stroke than that in the high level group (OR = 6.818, P = 0.002). Decreased HDL cholesterol was correlated to the occurrence of AIS with DM, especially in the populations of aged ≦70 years.

Hepatitis C Virus Replication Depends on Endosomal Cholesterol Homeostasis.

Science.gov (United States)

Stoeck, Ina Karen; Lee, Ji-Young; Tabata, Keisuke; Romero-Brey, Inés; Paul, David; Schult, Philipp; Lohmann, Volker; Kaderali, Lars; Bartenschlager, Ralf

2018-01-01

Similar to other positive-strand RNA viruses, hepatitis C virus (HCV) causes massive rearrangements of intracellular membranes, resulting in a membranous web (MW) composed of predominantly double-membrane vesicles (DMVs), the presumed sites of RNA replication. DMVs are enriched for cholesterol, but mechanistic details on the source and recruitment of cholesterol to the viral replication organelle are only partially known. Here we focused on selected lipid transfer proteins implicated in direct lipid transfer at various endoplasmic reticulum (ER)-membrane contact sites. RNA interference (RNAi)-mediated knockdown identified several hitherto unknown HCV dependency factors, such as steroidogenic acute regulatory protein-related lipid transfer domain protein 3 (STARD3), oxysterol-binding protein-related protein 1A and -B (OSBPL1A and -B), and Niemann-Pick-type C1 (NPC1), all residing at late endosome and lysosome membranes and required for efficient HCV RNA replication but not for replication of the closely related dengue virus. Focusing on NPC1, we found that knockdown or pharmacological inhibition caused cholesterol entrapment in lysosomal vesicles concomitant with decreased cholesterol abundance at sites containing the viral replicase factor NS5A. In untreated HCV-infected cells, unesterified cholesterol accumulated at the perinuclear region, partially colocalizing with NS5A at DMVs, arguing for NPC1-mediated endosomal cholesterol transport to the viral replication organelle. Consistent with cholesterol being an important structural component of DMVs, reducing NPC1-dependent endosomal cholesterol transport impaired MW integrity. This suggests that HCV usurps lipid transfer proteins, such as NPC1, at ER-late endosome/lysosome membrane contact sites to recruit cholesterol to the viral replication organelle, where it contributes to MW functionality. IMPORTANCE A key feature of the replication of positive-strand RNA viruses is the rearrangement of the host cell

Bile acids and lipids in isolated rat hepatocytes. II. Source of cholesterol used for bile acid formation, estimated by incorporation of tritium from tritiated water, and by the effect of ML-236B

NARCIS (Netherlands)

Kempen, H.J.; Vos Van Holstein, M.; Lange, J.de

1983-01-01

Chemicals/CAS: cholesterol, 57-88-5; cholic acid, 32500-01-9, 361-09-1, 81-25-4; colestyramine, 11041-12-6, 58391-37-0; compactin, 73573-88-3; lipid, 66455-18-3; tritium oxide, 14940-65-9; Bile Acids and Salts; Cholesterol, 57-88-5; Cholestyramine, 11041-12-6; compactin, 73573-88-3; Lipids;

Plasma cholesterol and related lipid levels of seemingly healthy ...

African Journals Online (AJOL)

The purpose of this study was achieved through analysis of fasting plasma samples for the following: Total cholesterol (TC), Triacylglycerols (TG), High density lipoprotein cholesterol (HDL), Low density lipoprotein cholesterol (LDL), and molar ratios of LDL/HDL, TC/ HDL, and TC/TG. Methods: One hundred and seventy four ...

Cholesterol in myelin biogenesis and hypomyelinating disorders.

Science.gov (United States)

Saher, Gesine; Stumpf, Sina Kristin

2015-08-01

The largest pool of free cholesterol in mammals resides in myelin membranes. Myelin facilitates rapid saltatory impulse propagation by electrical insulation of axons. This function is achieved by ensheathing axons with a tightly compacted stack of membranes. Cholesterol influences myelination at many steps, from the differentiation of myelinating glial cells, over the process of myelin membrane biogenesis, to the functionality of mature myelin. Cholesterol emerged as the only integral myelin component that is essential and rate-limiting for the development of myelin in the central and peripheral nervous system. Moreover, disorders that interfere with sterol synthesis or intracellular trafficking of cholesterol and other lipids cause hypomyelination and neurodegeneration. This review summarizes recent results on the roles of cholesterol in CNS myelin biogenesis in normal development and under different pathological conditions. This article is part of a Special Issue entitled Brain Lipids. Copyright © 2015 Elsevier B.V. All rights reserved.

Manipulation of Host Cholesterol by Obligate Intracellular Bacteria

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Dhritiman Samanta

2017-05-01

Full Text Available Cholesterol is a multifunctional lipid that plays important metabolic and structural roles in the eukaryotic cell. Despite having diverse lifestyles, the obligate intracellular bacterial pathogens Chlamydia, Coxiella, Anaplasma, Ehrlichia, and Rickettsia all target cholesterol during host cell colonization as a potential source of membrane, as well as a means to manipulate host cell signaling and trafficking. To promote host cell entry, these pathogens utilize cholesterol-rich microdomains known as lipid rafts, which serve as organizational and functional platforms for host signaling pathways involved in phagocytosis. Once a pathogen gains entrance to the intracellular space, it can manipulate host cholesterol trafficking pathways to access nutrient-rich vesicles or acquire membrane components for the bacteria or bacteria-containing vacuole. To acquire cholesterol, these pathogens specifically target host cholesterol metabolism, uptake, efflux, and storage. In this review, we examine the strategies obligate intracellular bacterial pathogens employ to manipulate cholesterol during host cell colonization. Understanding how obligate intracellular pathogens target and use host cholesterol provides critical insight into the host-pathogen relationship.

Secondary prevention care and effect: Total and low-density lipoprotein cholesterol levels and lipid-lowering drug use in women and men after incident myocardial infarction - The Tromsø Study 1994-2016.

Science.gov (United States)

Hopstock, Laila A; Eggen, Anne Elise; Løchen, Maja-Lisa; Mathiesen, Ellisiv B; Njølstad, Inger; Wilsgaard, Tom

2018-02-01

Secondary prevention guidelines after myocardial infarction (MI) are gender neutral, but underutilisation of treatment in women has been reported. We investigated the change in total and low-density lipoprotein (LDL) cholesterol levels and lipid-lowering drug (LLD) use after first-ever MI in a population-based study. We followed 10,005 participants (54% women) attending the Tromsø Study 1994-1995 and 8483 participants (55% women) attending the Tromsø Study 2007-2008 for first-ever MI up to their participation in 2007-2008 and 2015-2016, respectively. We used linear and logistic regression models to investigate sex differences in change in lipid levels. A total of 395 (MI cohort I) and 132 participants (MI cohort II) had a first-ever MI during 1994-2008 and 2007-2013, respectively. Mean change in total cholesterol was -2.34 mmol/L (SD 1.15) in MI cohort I, and in LDL cholesterol was -1.63 mmol/L (SD 1.12) in MI cohort II. Men had a larger decrease in lipid levels compared to women: the linear regression coefficient for change was -0.33 (95% confidence interval [CI] -0.51 to -0.14) for total cholesterol and -0.21 (95% CI -0.37 to -0.04) for LDL cholesterol, adjusted for baseline lipid value, age and cohort. Men had 73% higher odds (95% CI 1.15-2.61) of treatment target achievement compared to women, adjusted for baseline lipid value, age and cohort. LLD use was reported in 85% of women and 92% of men in MI cohort I, and 80% in women and 89% in men in MI cohort II. Compared to men, women had significantly less decrease in lipid levels after MI, and a smaller proportion of women achieved the treatment target.

Longitudinal Trend in Lipid Profile of Incident Peritoneal Dialysis Patients is Not Influenced by the Use of Biocompatible Solutions

Science.gov (United States)

Cho, Yeoungjee; Büchel, Janine; Steppan, Sonja; Passlick-Deetjen, Jutta; Hawley, Carmel M.; Dimeski, Goce; Clarke, Margaret; Johnson, David W.

2016-01-01

♦ Background: The longitudinal trends of lipid parameters and the impact of biocompatible peritoneal dialysis (PD) solutions on these levels remain to be fully defined. The present study aimed to a) evaluate the influence of neutral pH, low glucose degradation product (GDP) PD solutions on serum lipid parameters, and b) explore the capacity of lipid parameters (total cholesterol [TC], triglyceride [TG], high density lipoprotein [HDL], TC/HDL, low density lipoprotein [LDL], very low density lipoprotein [VLDL]) to predict cardiovascular events (CVE) and mortality in PD patients. ♦ Methods: The study included 175 incident participants from the balANZ trial with at least 1 stored serum sample. A composite CVE score was used as a primary clinical outcome measure. Multilevel linear regression and Poisson regression models were fitted to describe the trend of lipid parameters over time and its ability to predict composite CVE, respectively. ♦ Results: Small but statistically significant increases in serum TG (coefficient 0.006, p < 0.001), TC/HDL (coefficient 0.004, p = 0.001), and VLDL cholesterol (coefficient 0.005, p = 0.001) levels and a decrease in the serum HDL cholesterol levels (coefficient −0.004, p = 0.009) were observed with longer time on PD, whilst the type of PD solution (biocompatible vs standard) received had no significant effect on these levels. Peritoneal dialysis glucose exposure was significantly associated with trends in TG, TC/HDL, HDL and VLDL levels. Baseline lipid parameter levels were not predictive of composite CVEs or all-cause mortality. ♦ Conclusion: Serum TG, TC/HDL, and VLDL levels increased and the serum HDL levels decreased with increasing PD duration. None of the lipid parameters were significantly modified by biocompatible PD solution use over the time period studied or predictive of composite CVE or mortality. PMID:26429421

HYPOLIPEMIC THERAPY AND LOW SERUM CHOLESTEROL CONCENTRATION

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Vladmila Bojanic

2004-01-01

Full Text Available Low concentration of plasma lipoproteins (hypolipoproteinemia presents decreasing concentrations of all or particular lipids components. Classification of hypolipoproteinemia (hypoLP divides them into: primary (hereditary and secondary. Primary hipoLP are rare diseases and their main characteristic is disorder of apolipoproteins synthesis, which leads to low serum cholesterol concentration. Secondary hipoLP are presented in many diseases. They have diagnostic, prognostic significance and present good therapeutic marker. However, modern therapeutic approaches for aggressive lipid lowering pointed out many questions about physiological limits for cholesterol lowering. These approaches, also, open many questions about consequences of low serum concentration of total cholesterol and triglicerides.

Association between cholesterol plasma levels and craving among heroin users.

Science.gov (United States)

Lin, Shih-Hsien; Yang, Yen Kuang; Lee, Sheng-Yu; Hsieh, Pei Chun; Chen, Po See; Lu, Ru-Band; Chen, Kao Chin

2012-12-01

Lipids may play some roles in the central nervous system functions that are associated with drug addiction. To date, cholesterol is known to influence relapse of cocaine use. However, the relationship between cholesterol and heroin craving is unclear. This study examined the concurrent association between cholesterol and craving. The serum lipid levels of 70 heroin users who were undergoing or had undergone a methadone maintenance therapy were measured. Their craving and demographic data were assessed. Total cholesterol and low-density lipoprotein cholesterol are negatively associated with craving before (r = -0.33, P cognitive aspect of craving and may be a potential marker to predict risk of drug relapse.

Discovery and refinement of loci associated with lipid levels

DEFF Research Database (Denmark)

Willer, C. J.; Schmidt, E. M.; Sengupta, S.

2013-01-01

Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individ...... of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.......Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188......,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry...

Higher dietary intake of vitamin D may influence total cholesterol and carbohydrate profile independent of body composition in men with Chronic Spinal Cord Injury.

Science.gov (United States)

Beal, Christopher; Gorgey, Ashraf; Moore, Pamela; Wong, Nathan; Adler, Robert A; Gater, David

2018-07-01

A case-control design. To determine the effects of dietary vitamin D intake on insulin sensitivity (Si), glucose effectiveness (Sg), and lipid profile in individuals with spinal cord injury (SCI). 20 male, paraplegic (T3-L1) with chronic (> one year) motor complete SCI (AIS A or B) were recruited. Three-day dietary records were analyzed for dietary vitamin D (calciferol), and participants were assigned to one of two groups, a high vitamin D intake group and a low vitamin D intake group based on the mid-point of vitamin D frequency distribution. Individuals in both groups were matched based on age, weight, time since injury and level of injury. Sg, Si and lipid profiles were measured of the two groups. The high vitamin D group had an average intake of 5.33 ± 4.14 mcg compared to low vitamin D group, 0.74 ± 0.24 mcg. None of the 20 participants met the recommended guidelines for daily vitamin D intake. The higher vitamin D group had a significantly lower (P = 0.035) total cholesterol (148.00 ± 14.12 mg/dl) than the lower vitamin D group (171.80 ± 36.22 mg/dl). Vitamin D adjusted to total dietary intake was positively correlated to improvement in Si and Sg (PD intake. However, a higher dietary intake of vitamin D may influence total cholesterol and carbohydrate profile as demonstrated by a significant decrease in total cholesterol and improvement in glucose homeostasis independent of body composition changes after SCI.

CER-001, a HDL-mimetic, stimulates the reverse lipid transport and atherosclerosis regression in high cholesterol diet-fed LDL-receptor deficient mice.

Science.gov (United States)

Tardy, Claudine; Goffinet, Marine; Boubekeur, Nadia; Ackermann, Rose; Sy, Gavin; Bluteau, Alice; Cholez, Guy; Keyserling, Constance; Lalwani, Narendra; Paolini, John F; Dasseux, Jean-Louis; Barbaras, Ronald; Baron, Rudi

2014-01-01

CER-001 is a novel engineered HDL-mimetic comprised of recombinant human apoA-I and phospholipids that was designed to mimic the beneficial properties of nascent pre-β HDL. In this study, we have evaluated the capacity of CER-001 to perform reverse lipid transport in single dose studies as well as to regress atherosclerosis in LDLr(-/-) mice after short-term multiple-dose infusions. CER-001 induced cholesterol efflux from macrophages and exhibited anti-inflammatory response similar to natural HDL. Studies with HUVEC demonstrated CER-001 at a concentration of 500 μg/mL completely suppressed the secretion of cytokines IL-6, IL-8, GM-CSF and MCP-1. Following infusion of CER-001 (10mg/kg) in C57Bl/6J mice, we observed a transient increase in the mobilization of unesterified cholesterol in HDL particles containing recombinant human apoA-I. Finally we show that cholesterol elimination was stimulated in CER-001 treated animals as demonstrated by the increased cholesterol concentration in liver and feces. In a familial hypercholesterolemia mouse model (LDL-receptor deficient mice), the infusion of CER-001 caused 17% and 32% reductions in plaque size, 17% and 23% reductions in lipid content after 5 and 10 doses given every 2 days, respectively. Also, there was an 80% reduction in macrophage content in the plaque following 5 doses, and decreased VCAM-1 expression by 16% and 22% in the plaque following 5 and 10 intravenous doses of CER-001, respectively. These data demonstrate that CER-001 rapidly enhances reverse lipid transport in the mouse, reducing vascular inflammation and promoting regression of diet-induced atherosclerosis in LDLr(-/-) mice upon a short-term multiple dose treatment. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Physical activity, high density lipoprotein cholesterol and other lipids levels, in men and women from the ATTICA study

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Papaioannou Ioanna

2003-06-01

Full Text Available Abstract Background Physical activity has long been associated with reduced risk of coronary heart disease (CHD. In this work we evaluated the effect of physical activity on lipid levels, in a sample of cardiovascular disease free people. Methods The ATTICA study is a population – based cohort that has randomly enrolled 2772 individuals, stratified by age – gender (according to the census 2001, from the greater area of Athens, during 2001–2002. Of them, 1376 were men (45 ± 12 years old, range: 18 – 86 and 1396 women (45 ± 13 years old, range: 18 – 88. We assessed the relationship between physical activity status (measured in kcal/min expended per day and several lipids, after taking into account the effect of several characteristics of the participants. Results 578 (42% men and 584 (40% women were classified as physically active. Compared to sedentary physically active women had significantly lower levels of total serum cholesterol (p Conclusions Substantial independent increases in HDL-cholesterol and apolipoprotein A1 concentrations were observed in women, but not in men, in a Mediterranean cohort.

Lack of association of ghrelin precursor gene variants and percentage body fat or serum lipid profiles.

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Martin, Glynn R; Loredo, J C; Sun, Guang

2008-04-01

Ghrelin has been recognized for its involvement in food intake, control of energy homeostasis, and lipid metabolism. However, the roles of genetic variations in the ghrelin precursor gene (GHRL) on body compositions and serum lipids are not clear in humans. Our study investigated five single-nucleotide polymorphisms (SNPs) within GHRL to determine their relationship with body fat percentage (BF), trunk fat percentage (TF), lower body (legs) fat percentage (LF), and serum lipids in 1,464 subjects, which were recruited from the genetically homogeneous population of Newfoundland and Labrador (NL), Canada. Serum glucose, insulin, total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, and triglycerides were determined. Five SNPs are rs35684 (A/G: a transition substitution in exon 1), rs4684677 (A/T: a missense mutation), rs2075356 (C/T: intron), rs26802 (G/T: intron), and rs26311 (A/G: near the 3' untranslated region) of GHRL were genotyped using TaqMan validated or functionally tested SNP genotyping assays. Our study found no significant evidence of an allele or genotype association between any of the variant sites and body compositions or serum lipids. Furthermore, haplotype frequencies were not found to be significantly different between lean and obese subjects. In summary, the results of our study do not support a significant role for genetic variations in GHRL in the differences of body fat and serum lipid profiles in the NL population.

Genetic architecture of circulating lipid levels

DEFF Research Database (Denmark)

Demirkan, Ayşe; Amin, Najaf; Isaacs, Aaron

2011-01-01

Serum concentrations of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs) and total cholesterol (TC) are important heritable risk factors for cardiovascular disease. Although genome-wide association studies (GWASs) of circulating lipid...... the ENGAGE Consortium GWAS on serum lipids, were applied to predict lipid levels in an independent population-based study, the Rotterdam Study-II (RS-II). We additionally tested for evidence of a shared genetic basis for different lipid phenotypes. Finally, the polygenic score approach was used to identify...... an alternative genome-wide significance threshold before pathway analysis and those results were compared with those based on the classical genome-wide significance threshold. Our study provides evidence suggesting that many loci influencing circulating lipid levels remain undiscovered. Cross-prediction models...

Effects of aerobic exercise on lipids and lipoproteins.

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Wang, Yating; Xu, Danyan

2017-07-05

Dyslipidemia is the risk of cardiovascular disease, and their relationship is clear. Lowering serum cholesterol can reduce the risk of coronary heart disease. At present, the main treatment is taking medicine, however, drug treatment has its limitations. Exercise not only has a positive effect on individuals with dyslipidemia, but can also help improve lipids profile. This review is intending to provide information on the effects of exercise training on both tranditional lipids, for example, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides and new lipids and lipoproteins such as non-high-density lipoprotein cholesterol, and postprandial lipoprotein. The mechanisms of aerobic exercise on lipids and lipoproteins are also briefly described.

Interaction of pathogens with host cholesterol metabolism.

Science.gov (United States)

Sviridov, Dmitri; Bukrinsky, Michael

2014-10-01

Pathogens of different taxa, from prions to protozoa, target cellular cholesterol metabolism to advance their own development and to impair host immune responses, but also causing metabolic complications, for example, atherosclerosis. This review describes recent findings of how pathogens do it. A common theme in interaction between pathogens and host cholesterol metabolism is pathogens targeting lipid rafts of the host plasma membrane. Many intracellular pathogens use rafts as an entry gate, taking advantage of the endocytic machinery and high abundance of outward-looking molecules that can be used as receptors. At the same time, disruption of the rafts' functional capacity, achieved by the pathogens through a number of various means, impairs the ability of the host to generate immune response, thus helping pathogen to thrive. Pathogens cannot synthesize cholesterol, and salvaging host cholesterol helps pathogens build advanced cholesterol-containing membranes and assembly platforms. Impact on cholesterol metabolism is not limited to the infected cells; proteins and microRNAs secreted by infected cells affect lipid metabolism systemically. Given an essential role that host cholesterol metabolism plays in pathogen development, targeting this interaction may be a viable strategy to fight infections, as well as metabolic complications of the infections.

Raman probing of lipids, proteins, and mitochondria in skeletal myocytes: a case study on obesity

DEFF Research Database (Denmark)

Brazhe, Nadezda A.; Nikelshparg, Evelina I.; Prats, Clara

2017-01-01

We propose a novel approach to assess simultaneously lipid composition in lipid droplets, the redox state of cytochromes, and the relative amount of [Fe–S] clusters in the electron transport chain in the mitochondria of skeletal myocytes by means of near-infrared Raman spectroscopy. Mitochondria...... technique allows to estimate qualitatively the relative amount of cholesterol and unsaturated lipids, ordering of lipid phase in lipid droplets, changes in the redox state of c-type and b-type cytochromes, and the relative amount of [Fe–S] clusters in the mitochondria of intact myocytes. The proposed...

Future directions in lipid therapies.

Science.gov (United States)

Ansell, Benjamin

2002-01-01

Cholesterol management to reduce the burden of cardiovascular disease is a major public health concern. Despite widespread recognition of lipid abnormalities as cardiovascular risk factors, significant cardiovascular event reductions with cholesterol-lowering therapies, and dissemination of treatment guidelines, most high-risk patients are not at target lipid levels. In addition to lifestyle changes, four major drug classes are available to modify lipid levels: fibrates, niacin, resins, and statins. High efficacy and tolerability in clinical trials make statins the most widely prescribed of these agents. Newer, more potent members of this class and novel formulations of niacin and resins may provide more effective therapy for dyslipidemia with fewer side effects. Several agents in development (cholesterol-absorption inhibitors and ACAT inhibitors) exploit mechanisms of action complementary to those of current treatments and combined with statins may produce greater improvements in lipid profiles than are now possible. These innovations should enable a greater number of patients to achieve more aggressive cholesterol goals, thereby reducing the risk of cardiovascular events.

Interrelationships of spontaneous growth hormone axis activity, body fat, and serum lipids in healthy elderly women and men.

Science.gov (United States)

O'Connor, K G; Harman, S M; Stevens, T E; Jayme, J J; Bellantoni, M F; Busby-Whitehead, M J; Christmas, C; Münzer, T; Tobin, J D; Roy, T A; Cottrell, E; St Clair, C; Pabst, K M; Blackman, M R

1999-11-01

Aging is associated with decreased growth hormone (GH) secretion and plasma insulin-like growth factor-I (IGF-I) levels, increased total and abdominal fat, total and low-density lipoprotein (LDL) cholesterol, and triglycerides, and reduced high-density lipoprotein (HDL) cholesterol. Similar changes in lipids and body composition occur in nonelderly GH-deficient adults and are reversed with GH administration. To examine whether GH/IGF-I axis function in the elderly is related to the lipid profile independently of body fat, we evaluated GH secretion, serum IGF-I and IGF binding protein-3 (IGFBP-3) levels, adiposity via the body mass index (BMI), waist to hip ratio (WHR), dual-energy x-ray absorptiometry (DEXA), and magnetic resonance imaging (MRI), and circulating lipids in 101 healthy subjects older than 65 years. Integrated nocturnal GH secretion (log IAUPGH) was inversely related (P HDL cholesterol (P HDL cholesterol was inversely related to the WHR (P body fat, to be an independent determinant of total (P HDL cholesterol (P HDL in women (P body fat or lipid measures, except for a positive correlation of IGF-I with triglycerides in men. Thus, endogenous nocturnal GH secretion predicts total, LDL, and HDL cholesterol levels independently of total or abdominal fat, suggesting that it is an independent cardiometabolic risk factor in healthy elderly people.

Lxr-driven enterocyte lipid droplet formation delays transport of ingested lipids.

Science.gov (United States)

Cruz-Garcia, Lourdes; Schlegel, Amnon

2014-09-01

Liver X receptors (Lxrs) are master regulators of cholesterol catabolism, driving the elimination of cholesterol from the periphery to the lumen of the intestine. Development of pharmacological agents to activate Lxrs has been hindered by synthetic Lxr agonists' induction of hepatic lipogenesis and hypertriglyceridemia. Elucidating the function of Lxrs in regulating enterocyte lipid handling might identify novel aspects of lipid metabolism that are pharmacologically amenable. We took a genetic approach centered on the single Lxr gene nr1h3 in zebrafish to study the role of Lxr in enterocyte lipid metabolism. Loss of nr1h3 function causes anticipated gene regulatory changes and cholesterol intolerance, collectively reflecting high evolutionary conservation of zebrafish Lxra function. Intestinal nr1h3 activation delays transport of absorbed neutral lipids, with accumulation of neutral lipids in enterocyte cytoplasmic droplets. This delay in transport of ingested neutral lipids protects animals from hypercholesterolemia and hepatic steatosis induced by a high-fat diet. On a gene regulatory level, Lxra induces expression of acsl3a, which encodes acyl-CoA synthetase long-chain family member 3a, a lipid droplet-anchored protein that directs fatty acyl chains into lipids. Forced overexpression of acls3a in enterocytes delays, in part, the appearance of neutral lipids in the vasculature of zebrafish larvae. Activation of Lxr in the intestine cell-autonomously regulates the rate of delivery of absorbed lipids by inducting a temporary lipid intestinal droplet storage depot. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.

Effect of tofacitinib on lipid levels and lipid-related parameters in patients with moderate to severe psoriasis.

Science.gov (United States)

Wolk, Robert; Armstrong, Ehrin J; Hansen, Peter R; Thiers, Bruce; Lan, Shuping; Tallman, Anna M; Kaur, Mandeep; Tatulych, Svitlana

Psoriasis is a systemic inflammatory disease associated with increased cardiovascular (CV) risk and altered lipid metabolism. Tofacitinib is an oral Janus kinase inhibitor. The aim of the study was to investigate the effects of tofacitinib on traditional and nontraditional lipid parameters and CV risk markers in patients with psoriasis from a phase III study, OPT Pivotal 1. Patients with psoriasis were randomized to tofacitinib 5 or 10 mg twice daily (BID) or placebo BID. Serum samples were collected at baseline, week 4, and week 16. Analyses included serum cholesterol levels, triglycerides, lipoproteins, lipid particles, lipid-related parameters/CV risk markers, and high-density lipoprotein (HDL) function analyses. At week 16, small concurrent increases in mean low-density lipoprotein cholesterol (LDL-C) and HDL cholesterol (HDL-C) levels were observed with tofacitinib; total cholesterol/HDL-C ratio did not change. There was no significant change in the number of small dense LDL particles, which are considered to be more atherogenic than large particles, and oxidized LDL did not increase. Paraoxonase 1 activity, linked to HDL antioxidant capacity, increased, and HDL-associated serum amyloid A, which reduces the anti-atherogenic potential of HDL, decreased. HDL capacity to promote cholesterol efflux from macrophages did not change. Lecithin-cholesterol acyltransferase activity, which is associated with reverse cholesterol transport, increased. Markers of systemic inflammation, serum amyloid A and C-reactive protein, decreased with tofacitinib. While small increases in lipid levels are observed with tofacitinib treatment in patients with psoriasis, effects on selected lipid-related parameters and other circulating CV risk biomarkers are not suggestive of an increased CV risk [NCT01276639]. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Postprandial lipid responses of butter blend containing fish oil in a single-meal study in humans

DEFF Research Database (Denmark)

Overgaard, Julie; Porsgaard, Trine; Guo, Zheng

2008-01-01

blend with fish oil (352 mg n-3 long-chain PUFA (LCPUFA)) or the commercial butter blend. Blood samples were collected after the meals and in the fasting condition on the test day and the following morning, and were analysed for cholesterol absorption, plasma lipid profile and fatty acid composition....... No significant difference in the postprandial plasma fatty acid composition was observed between the groups, neither difference in cholesterol absorption, plasma cholesterol or the cholesterol contents of plasma lipoproteins. The incorporation of fish oil in the butter resulted in a significant lower......The postprandial effects of a butter product containing fish oil were investigated in a single-meal, randomized crossover study with a commercial butter product as the control. Twelve healthy males consumed two test meals with (13)C-labelled cholesterol (45 mg) and either an interesterified butter...

Spontaneous insertion of GPI anchors into cholesterol-rich membrane domains

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Jing Li

2018-05-01

Full Text Available GPI-Anchored proteins (GPI-APs can be exogenously transferred onto bilayer membranes both in vivo and in vitro, while the mechanism by which this transfer process occurs is unknown. In this work, we used atomistic molecular dynamics simulations and free energy calculations to characterize the essential influence of cholesterol on insertion of the GPI anchors into plasma membranes. We demonstrate, both dynamically and energetically, that in the presence of cholesterol, the tails of GPI anchors are able to penetrate inside the core of the lipid membrane spontaneously with a three-step mechanism, while in the absence of cholesterol no spontaneous insertion was observed. We ascribe the failure of insertion to the strong thermal fluctuation of lipid molecules in cholesterol-free bilayer, which generates a repulsive force in entropic origin. In the presence of cholesterol, however, the fluctuation of lipids is strongly reduced, thus decreasing the barrier for the anchor insertion. Based on this observation, we propose a hypothesis that addition of cholesterol creates vertical creases in membranes for the insertion of acyl chains. Moreover, we find that the GPI anchor could also spontaneously inserted into the boundary between cholesterol-rich and cholesterol-depleted domains. Our results shed light on the mechanism of cholesterol-mediated interaction between membrane proteins with acyl chain and plasma membranes in living cells.

Spontaneous insertion of GPI anchors into cholesterol-rich membrane domains

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Li, Jing; Liu, Xiuhua; Tian, Falin; Yue, Tongtao; Zhang, Xianren; Cao, Dapeng

2018-05-01

GPI-Anchored proteins (GPI-APs) can be exogenously transferred onto bilayer membranes both in vivo and in vitro, while the mechanism by which this transfer process occurs is unknown. In this work, we used atomistic molecular dynamics simulations and free energy calculations to characterize the essential influence of cholesterol on insertion of the GPI anchors into plasma membranes. We demonstrate, both dynamically and energetically, that in the presence of cholesterol, the tails of GPI anchors are able to penetrate inside the core of the lipid membrane spontaneously with a three-step mechanism, while in the absence of cholesterol no spontaneous insertion was observed. We ascribe the failure of insertion to the strong thermal fluctuation of lipid molecules in cholesterol-free bilayer, which generates a repulsive force in entropic origin. In the presence of cholesterol, however, the fluctuation of lipids is strongly reduced, thus decreasing the barrier for the anchor insertion. Based on this observation, we propose a hypothesis that addition of cholesterol creates vertical creases in membranes for the insertion of acyl chains. Moreover, we find that the GPI anchor could also spontaneously inserted into the boundary between cholesterol-rich and cholesterol-depleted domains. Our results shed light on the mechanism of cholesterol-mediated interaction between membrane proteins with acyl chain and plasma membranes in living cells.

Effects of chromium-enriched bacillus subtilis KT260179 supplementation on chicken growth performance, plasma lipid parameters, tissue chromium levels, cecal bacterial composition and breast meat quality.

Science.gov (United States)

Yang, Jiajun; Qian, Kun; Zhang, Wei; Xu, Yayuan; Wu, Yijing

2016-11-08

Both chromium (Cr) and probiotic bacillus own the virtues of regulating animal metabolism and meat quality. Purpose of this study was to evaluate the efficiency of supplemental Cr and bacillus in the form of chromium-enriched Bacillus subtilis KT260179 (CEBS) on chicken growth performance, plasma lipid parameters, tissue chromium levels, cecal bacterial composition and breast meat quality. Six hundred of 1-day-old Chinese Huainan Partridge chickens were divided into four groups randomly: Control, inorganic Cr, Bacillus subtilis, and CEBS. The feed duration was 56 days. After 28 days of treatment, broiler feed CEBS or normal B. subtilis had higher body weights than control broiler, and after 56 days, chickens given either CEBS or B. subtilis had greater body weights than control broiler or those given inorganic Cr. Plasma total cholesterol, triglycerides, and low density lipoprotein cholesterol levels declined significantly in the CEBS group compared with the control, whereas plasma high density lipoprotein cholesterol levels increased significantly. The concentration of Cr in blood and breast muscle increased after CEBS and inorganic Cr supplementation. B. subtilis and CEBS supplementation caused a significant increase in the numbers of Lactobacillus and Bifidobacterium in the caecum, while the numbers of Escherichia coli and Salmonella decreased significantly compared to the control. Feed adding CEBS increased the lightness, redness, and yellowness of breast meat, improved the water-holding capacity, decreased the shear force and cooking loss. In all, CEBS supplementation promoted body growth, improved plasma lipid parameters, increased tissue Cr concentrations, altered cecal bacterial composition and improved breast meat quality.

Alzheimer’s disease prevention – The emerging role of lipids and diet

Directory of Open Access Journals (Sweden)

Hartmann Tobias

2007-05-01

Full Text Available Although Alzheimer’s disease (AD causes massive and irreversible neurodegeneration, prevention and curing early stages of the disease appears to represent a realistic goal to be achieved in future. In fact, one of the very first effective treatments available could be derived from ordinary food sources. Overproduction of the amyloidogenic peptide Aβ42 causes AD. Thus far two physiological regulatory cycles were identified in which Aβ peptides play a major role. These regulatory cycles are involved in cholesterol and sphingolipid homeostasis. Moreover, Aβ production is under physiological conditions tightly regulated and its production rate is highly sensitive to alterations of the cellular membrane composition. Several lipids, sterols and fatty acids have thus far been identified to affect Aβ production. Most knowledge thus far has been gathered about those lipids which are themselves are target of Aβ mediated lipid homeostasis, cholesterol and sphingomyelin. E.g. cholesterol strongly increases Aβ production and cholesterol lowering with statins is a matter of intense clinical research not only for cardiovascular disease preventions but now also for AD therapy. Special interest received n-3 polyunsaturated fatty acids, especially DHA, because of their Aβ lowering effect in combination with favorable pharmacokinetics and neuroprotective properties.

Astragalus polysaccharides lowers plasma cholesterol through mechanisms distinct from statins.

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Yunjiu Cheng

Full Text Available To determine the efficacy and underlying mechanism of Astragalus polysaccharides (APS on plasma lipids in hypercholesterolemia hamsters. The effect of APS (0.25 g/kg/d on plasma and liver lipids, fecal bile acids and neutral sterol, cholesterol absorption and synthesis, HMG-CoA reductase activity, and gene and protein expressions in the liver and small intestine was investigated in twenty-four hypercholesterolemia hamsters. Treatment periods lasted for three months. APS significantly lowered plasma total cholesterol by 45.8%, triglycerides by 30%, and low-density lipoprotein-cholesterol by 47.4%, comparable to simvastatin. Further examinations revealed that APS reduced total cholesterol and triglycerides in the liver, increased fecal bile acid and neutral sterol excretion, inhibited cholesterol absorption, and by contrast, increased hepatic cholesterol synthesis and HMG-CoA reductase activity. Plasma total cholesterol or low-density lipoprotein-cholesterol levels were significantly correlated with cholesterol absorption rates. APS up-regulated cholesterol-7α-hydroxylase and LDL-receptor gene expressions. These new findings identify APS as a potential natural cholesterol lowering agent, working through mechanisms distinct from statins.

Molecular Transport Studies Through Unsupported Lipid Membranes

Science.gov (United States)

Rock, William; Parekh, Sapun; Bonn, Mischa

2014-03-01

Dendrimers, spherical polymeric nanoparticles made from branched monomers around a central core, show great promise as drug delivery vehicles. Dendrimer size, core contents, and surface functionality can be synthetically tuned, providing unprecedented versatility. Polyamidoamine (PAMAM) dendrimers have been shown to enter cells; however, questions remain about their biophysical interactions with the cell membrane, specifically about the presence and size of transient pores. We monitor dendrimer-lipid bilayer interactions using unsupported black lipid membranes (BLMs) as model cell membranes. Custom bilayer slides contain two vertically stacked aqueous chambers separated by a 25 μm Teflon sheet with a 120 μm aperture where the bilayer is formed. We vary the composition of model membranes (cholesterol content and lipid phase) to create biomimetic systems and study the interaction of PAMAM G6 and G3 dendrimers with these bilayers. Dendrimers, dextran cargo, and bilayers are monitored and quantified using time-lapse fluorescence imaging. Electrical capacitance measurements are simultaneously recorded to determine if the membrane is porous, and the pore size is deduced by monitoring transport of fluorescent dextrans of increasing molecular weight. These experiments shed light on the importance of cholesterol content and lipid phase on the interaction of dendrimer nanoparticles with membranes.

Plasma HDL-cholesterol and triglycerides, but not LDL-cholesterol, are associated with insulin secretion in non-diabetic subjects.

Science.gov (United States)

Natali, Andrea; Baldi, Simona; Bonnet, Fabrice; Petrie, John; Trifirò, Silvia; Tricò, Domenico; Mari, Andrea

2017-04-01

Experimental data support the notion that lipoproteins might directly affect beta cell function, however clinical data are sparse and inconsistent. We aimed at verifying whether, independently of major confounders, serum lipids are associated with alterations in insulin secretion or clearance non-diabetic subjects. Cross sectional and observational prospective (3.5yrs), multicentre study in which 1016 non-diabetic volunteers aged 30-60yrs. and with a wide range of BMI (20.0-39.9kg/m 2 ) were recruited in a setting of University hospital ambulatory care (RISC study). baseline fasting lipids, fasting and OGTT-induced insulin secretion and clearance (measured by glucose and C-peptide modeling), peripheral insulin sensitivity (by the euglycemic clamp). Lipids and OGTT were repeated in 980 subjects after 3.5years. LDL-cholesterol did not show independent associations with fasting or stimulated insulin secretion or clearance. After accounting for potential confounders, HDL-cholesterol displayed negative and triglycerides positive independent associations with fasting and OGTT insulin secretion; neither with insulin clearance. Low HDL-cholesterol and high triglycerides were associated with an increase in glucose-dependent and a decrease in non-glucose-dependent insulin secretion. Over 3.5years both an HDL-cholesterol decline and a triglycerides rise were associated with an increase in fasting insulin secretion independent of changes in body weight or plasma glucose. LDL-cholesterol does not seem to influence any major determinant of insulin bioavailability while low HDL-cholesterol and high triglycerides might contribute to sustain the abnormalities in insulin secretion that characterize the pre-diabetic state. Copyright © 2017 Elsevier Inc. All rights reserved.

Association between hepatic cholesterol and oleic acid in the liver of rats treated with partially hydrogenated vegetable oil

Directory of Open Access Journals (Sweden)

Gabriela Salim Ferreira de Castro

2012-02-01

Full Text Available OBJECTIVE: The aim of the present study was to investigate the lipid profiles of the hepatic and adipose tissues of Wistar rats treated for 21 days with a diet high in saturated fat (high saturated fat, n=6 or high in hydrogenated fat, that is, having 50% partially hydrogenated vegetable oil in its composition (high hydrogenated fat, n=6, and compare them to those of a control group (control group, n=6. METHODS: Adipose tissue and total hepatic fat were higher in the saturated fat group than in the hydrogenated fat group. Hepatic lipid peroxidation was greatest in the saturated fat group, with consequent lower hepatic vitamin E and A levels. In contrast, serum vitamin A was highest in the saturated fat group. Analysis of hepatic lipid fractions found more cholesterol and less high density lipoprotein-cholesterol in the hydrogenated fat group. The hydrogenated fat group had the highest levels of triacylglycerols, followed by the saturated fat group. RESULTS: Significant amounts of trans fatty acids were detected in the hepatic and adipose tissues of the hydrogenated fat group. Among the identified fatty acids, 18:1n9 had a higher positive association with hepatic cholesterol and triacylglycerols, and a higher negative association with high density lipoprotein-cholesterol. Partially hydrogenated vegetable oil promotes greater accumulation of cholesterol and triacylglycerols in the liver than saturated fats. CONCLUSION: Trans fatty acids were incorporated into hepatocytes and adipocytes in a highly efficient manner.

Conservation of lipid metabolic gene transcriptional regulatory networks in fish and mammals.

Science.gov (United States)

Carmona-Antoñanzas, Greta; Tocher, Douglas R; Martinez-Rubio, Laura; Leaver, Michael J

2014-01-15

Lipid content and composition in aquafeeds have changed rapidly as a result of the recent drive to replace ecologically limited marine ingredients, fishmeal and fish oil (FO). Terrestrial plant products are the most economic and sustainable alternative; however, plant meals and oils are devoid of physiologically important cholesterol and long-chain polyunsaturated fatty acids (LC-PUFA), eicosapentaenoic (EPA), docosahexaenoic (DHA) and arachidonic (ARA) acids. Although replacement of dietary FO with vegetable oil (VO) has little effect on growth in Atlantic salmon (Salmo salar), several studies have shown major effects on the activity and expression of genes involved in lipid homeostasis. In vertebrates, sterols and LC-PUFA play crucial roles in lipid metabolism by direct interaction with lipid-sensing transcription factors (TFs) and consequent regulation of target genes. The primary aim of the present study was to elucidate the role of key TFs in the transcriptional regulation of lipid metabolism in fish by transfection and overexpression of TFs. The results show that the expression of genes of LC-PUFA biosynthesis (elovl and fads2) and cholesterol metabolism (abca1) are regulated by Lxr and Srebp TFs in salmon, indicating highly conserved regulatory mechanism across vertebrates. In addition, srebp1 and srebp2 mRNA respond to replacement of dietary FO with VO. Thus, Atlantic salmon adjust lipid metabolism in response to dietary lipid composition through the transcriptional regulation of gene expression. It may be possible to further increase efficient and effective use of sustainable alternatives to marine products in aquaculture by considering these important molecular interactions when formulating diets. © 2013.

Nanoscale Membrane Domain Formation Driven by Cholesterol

DEFF Research Database (Denmark)

Javanainen, Matti; Martinez-Seara, Hector; Vattulainen, Ilpo

2017-01-01

Biological membranes generate specific functions through compartmentalized regions such as cholesterol-enriched membrane nanodomains that host selected proteins. Despite the biological significance of nanodomains, details on their structure remain elusive. They cannot be observed via microscopic...... dipalmitoylphosphatidylcholine and cholesterol - the "minimal standard" for nanodomain formation. The simulations reveal how cholesterol drives the formation of fluid cholesterol-rich nanodomains hosting hexagonally packed cholesterol-poor lipid nanoclusters, both of which show registration between the membrane leaflets....... The complex nanodomain substructure forms when cholesterol positions itself in the domain boundary region. Here cholesterol can also readily flip-flop across the membrane. Most importantly, replacing cholesterol with a sterol characterized by a less asymmetric ring region impairs the emergence of nanodomains...

Serum Lipid Profile: Fasting or Non-fasting?

OpenAIRE

Nigam, P. K.

2010-01-01

Serum lipid profile has now become almost a routine test. It is usually done in fasting state due to certain limitations in non-fasting serum sample. In the recent past efforts have been made to simplify blood sampling by replacing fasting lipid profile with non-fasting lipid profile. However, fasting specimen is preferred if cardiovascular risk assessment is based on total cholesterol, LDL cholesterol or non-HDL cholesterol. A lot has yet to be done in this area. Till then we have to believe...

Lxr-driven enterocyte lipid droplet formation delays transport of ingested lipids[S

OpenAIRE

Cruz-Garcia, Lourdes; Schlegel, Amnon

2014-01-01

Liver X receptors (Lxrs) are master regulators of cholesterol catabolism, driving the elimination of cholesterol from the periphery to the lumen of the intestine. Development of pharmacological agents to activate Lxrs has been hindered by synthetic Lxr agonists’ induction of hepatic lipogenesis and hypertriglyceridemia. Elucidating the function of Lxrs in regulating enterocyte lipid handling might identify novel aspects of lipid metabolism that are pharmacologically amenable. We took a geneti...

Molecular interactions between bile salts, phospholipids and cholesterol : relevance to bile formation, cholesterol crystallization and bile salt toxicity

NARCIS (Netherlands)

Moschetta, Antonio

2001-01-01

Cholesterol is a nonpolar lipid dietary constituent, absorbed from the small intestine, transported in blood and taken up by the liver. In bile, the sterol is solubilized in mixed micelles by bile salts and phospholipids. In case of supersaturation, cholesterol is kept in vesicles with phospholipid

Effects of Lactobacillus fermented soymilk and soy yogurt on hepatic lipid accumulation in rats fed a cholesterol-free diet.

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Kitawaki, Ryoko; Nishimura, Yuko; Takagi, Naohiro; Iwasaki, Mitsuhiro; Tsuzuki, Kimiko; Fukuda, Mitsuru

2009-07-01

We examined the effects of lactic acid fermented soymilk, in which part of the soymilk was replaced with okara (soy yogurt), on plasma and hepatic lipid profiles in rats fed a cholesterol-free diet. Additionally, we investigated the effects of soy yogurt on hepatic gene expression in rats using DNA microarray analysis. Male Sprague-Dawley rats aged 5 weeks (n=5/group) were fed a control diet (AIN-93) or a test diet in which 20% of the diet was replaced by soy yogurt for 7 weeks. Soy yogurt consumption did not affect body weight or adipose tissue weight as compared with control diet. In the soy yogurt group, the liver weight and hepatic triglyceride content were significantly lower than the control group, and the level of plasma cholesterol was also lower. Furthermore, DNA microarray analysis indicated that soy yogurt ingestion down-regulated the expression of the SREBP-1 gene and enzymes related to lipogenesis in the rat liver, while expression of beta-oxidation-related genes was up-regulated. These results suggest that soy yogurt is beneficial in preventing hepatic lipid accumulation in rats.

A Thermodynamic Study of the Effects of Cholesterol on the Interaction between Liposomes and Ethanol

DEFF Research Database (Denmark)

Trandum, Christa; Westh, Peter; Jørgensen, Kent

2000-01-01

The association of ethanol with unilamellar dimyristoyl phosphatidylcholine (DMPC) liposomes of varying cholesterol content has been investigated by isothermal titration calorimetry over a wide temperature range (8-45 degrees C). The calorimetric data show that the interaction of ethanol...... temperature region may play an important role for association of ethanol with the lipid bilayers. Finally, the relation between cholesterol content and the affinity of ethanol for the lipid bilayer provides some support for the in vivo observation that cholesterol acts as a natural antagonist against alcohol...... of ethanol for the lipid bilayer compared to pure DMPC bilayers, whereas higher levels of cholesterol (>10 mol%) reduce affinity of ethanol for the lipid bilayer. Moreover, the experimental data reveal that the affinity of ethanol for the DMPC bilayers containing small amounts of cholesterol is enhanced...

Effect of different fat-enriched meats on non-cholesterol sterols and oxysterols as markers of cholesterol metabolism: Results of a randomized and cross-over clinical trial.

Science.gov (United States)

Baila-Rueda, L; Mateo-Gallego, R; Pérez-Calahorra, S; Lamiquiz-Moneo, I; de Castro-Orós, I; Cenarro, A; Civeira, F

2015-09-01

Different kinds of fatty acids can affect the synthesis, absorption, and elimination of cholesterol. This study was carried out to assess the associations of cholesterol metabolism with the intake of two meats with different fatty acid composition in healthy volunteers. The study group was composed of 20 subjects (12 males and eight females; age, 34.4 ± 11.6 years; body mass index (BMI), 23.5 ± 2.3 kg/m(2); low-density lipoprotein (LDL) cholesterol, 2.97 ± 0.55 mmol/l; high-density lipoprotein (HDL) cholesterol, 1.61 ± 0.31 mmol/l; triglycerides (TG), 1.06 ± 0.41 mmol/l) who completed a 30-day randomized and cross-over study to compare the cholesterol metabolism effect of 250 g of low-fat lamb versus 250 g of high-fat lamb per day in their usual diet. Cholesterol absorption, synthesis, and elimination were estimated from the serum non-cholesterol sterol and oxysterol concentrations analyzed by a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). No changes in weight, plasma lipids, or physical activity were observed across the study. Cholesterol intestinal absorption was decreased with both diets. Cholesterol synthesis and elimination decreased during the low-fat lamb dietary intervention (ρ = 0.048 and ρ = 0.005, respectively). Acute changes in the diet fat content modify the synthesis, absorption, and biliary elimination of cholesterol. These changes were observed even in the absence of total and LDL cholesterol changes in plasma. ClinicalTrials.gov PRS, NCT02259153. Copyright © 2015 Elsevier B.V. All rights reserved.

The Position of Aβ22-40 and Aβ1-42 in Anionic Lipid Membranes Containing Cholesterol.

Science.gov (United States)

Barrett, Matthew A; Alsop, Richard J; Hauß, Thomas; Rheinstädter, Maikel C

2015-11-30

Amyloid-β peptides interact with cell membranes in the human brain and are associated with neurodegenerative diseases, such as Alzheimer's disease. An emerging explanation of the molecular mechanism, which results in neurodegeneration, places the cause of neurotoxicity of the amyloid- peptides on their potentially negative interaction with neuronal membranes. It is known that amyloid-β peptides interact with the membrane, modifying the membrane's structural and dynamic properties. We present a series of X-ray diffraction experiments on anionic model lipid membranes containing various amounts of cholesterol. These experiments provide experimental evidence for an interaction of both the full length amyloid-β1-42 peptide, and the peptide fragment amyloid-β22-40 with anionic bilayer containing cholesterol. The location of the amyloid-β peptides was determined from these experiments, with the full length peptide embedding into the membrane, and the peptide fragment occupying 2 positions-on the membrane surface and embedded into the membrane core.

Tofacitinib restores the inhibition of reverse cholesterol transport induced by inflammation: understanding the lipid paradox associated with rheumatoid arthritis.

Science.gov (United States)

Pérez-Baos, S; Barrasa, J I; Gratal, P; Larrañaga-Vera, A; Prieto-Potin, I; Herrero-Beaumont, G; Largo, R

2017-09-01

Patients with active rheumatoid arthritis (RA) have increased cardiovascular mortality, paradoxically associated with reduced circulating lipid levels. The JAK inhibitor tofacitinib ameliorates systemic and joint inflammation in RA with a concomitant increase in serum lipids. We analysed the effect of tofacitinib on the lipid profile of hyperlipidaemic rabbits with chronic arthritis (CA) and on the changes in reverse cholesterol transport (RCT) during chronic inflammation. CA was induced in previously immunized rabbits, fed a high-fat diet, by administering four intra-articular injections of ovalbumin. A group of rabbits received tofacitinib (10 mg·kg -1 ·day -1 ) for 2 weeks. Systemic and synovial inflammation and lipid content were evaluated. For in vitro studies, THP-1-derived macrophages were exposed to high lipid concentrations and then stimulated with IFNγ in the presence or absence of tofacitinib in order to study mediators of RCT. Tofacitinib decreased systemic and synovial inflammation and increased circulating lipid levels. Although it did not modify synovial macrophage density, it reduced the lipid content within synovial macrophages. In foam macrophages in culture, IFNγ further stimulated intracellular lipid accumulation, while the JAK/STAT inhibition provoked by tofacitinib induced lipid release by increasing the levels of cellular liver X receptor α and ATP-binding cassette transporter (ABCA1) synthesis. Active inflammation could be associated with lipid accumulation within macrophages of CA rabbits. JAK inhibition induced lipid release through RCT activation, providing a plausible explanation for the effect of tofacitinib on the lipid profile of RA patients. © 2017 The British Pharmacological Society.

Melanocortin signaling in the CNS directly regulates circulating cholesterol

OpenAIRE

Perez-Tilve, Diego; Hofmann, Susanna M; Basford, Joshua; Nogueiras, Ruben; Pfluger, Paul T; Patterson, James T; Grant, Erin; Wilson-Perez, Hilary E; Granholm, Norman A; Arnold, Myrtha; Trevaskis, James L; Butler, Andrew A; Davidson, William S; Woods, Stephen C; Benoit, Stephen C

2010-01-01

Cholesterol circulates in the blood in association with triglycerides and other lipids, and elevated blood low-density lipoprotein cholesterol carries a risk for metabolic and cardiovascular disorders, whereas high-density lipoprotein (HDL) cholesterol in the blood is thought to be beneficial. Circulating cholesterol is the balance among dietary cholesterol absorption, hepatic synthesis and secretion, and the metabolism of lipoproteins by various tissues. We found that the CNS is also an impo...

Lipid Raft Size and Lipid Mobility in Non-raft Domains Increase during Aging and Are Exacerbated in APP/PS1 Mice Model of Alzheimer's Disease. Predictions from an Agent-Based Mathematical Model

Science.gov (United States)

Santos, Guido; Díaz, Mario; Torres, Néstor V.

2016-01-01

A connection between lipid rafts and Alzheimer's disease has been studied during the last decades. Mathematical modeling approaches have recently been used to correlate the effects of lipid composition changes in the physicochemical properties of raft-like membranes. Here we propose an agent based model to assess the effect of lipid changes in lipid rafts on the evolution and progression of Alzheimer's disease using lipid profile data obtained in an established model of familial Alzheimer's disease. We have observed that lipid raft size and lipid mobility in non-raft domains are two main factors that increase during age and are accelerated in the transgenic Alzheimer's disease mouse model. The consequences of these changes are discussed in the context of neurotoxic amyloid β production. Our agent based model predicts that increasing sterols (mainly cholesterol) and long-chain polyunsaturated fatty acids (LCPUFA) (mainly DHA, docosahexaenoic acid) proportions in the membrane composition might delay the onset and progression of the disease. PMID:27014089

Serum lipids coupled with menopausal status may be used as biomarkers in female gallstone patients

International Nuclear Information System (INIS)

Awan, A.Y.; Channa, N.A.; Solangi, D.A.; Tabassum, N.

2017-01-01

Objective: Females with different menopausal status are compared for serum lipids to explore the role of menopausal status in developing gallstones. Methodology: This study was conducted at Institute of Biochemistry, University of Sindh Jamshoro, Pakistan. A total number of 135 female gallstone patients admitted at Liaquat University Hospital, Wali Bhai Rajputana Hospital, Hyderabad and other hospitals of Hyderabad, Pakistan and 170 age and gender matched control subjects were selected for the study. The serum samples of patients of different menopausal status and control group were analyzed for the lipid contents. Gallstones recovered from the patients were also analyzed for the composition by FTIR. Results: Serum total cholesterol (TC) and serum high density lipoprotein cholesterol (HDL-C) were significantly varied among all age groups while serum triglycerides (TG), serum very low density lipoprotein cholesterol (VLDL-C) and serum total lipids (TL) were found to be significantly differed among four different types of gallstone formers. Consumers of non-branded oil and non-branded ghee were found with significant lipid alterations in comparison to control group. Major lipid alterations were found in female gallstone patients with pre and peri-menopause. Conclusion: Raised serum TC, serum TG and decreased serum HDL-C in addition to pre- and peri-menopausal status may be considered as biomarkers for female gallstone patients.

Changes in the serum profiles of lipids and cholesterol in sheep ...

African Journals Online (AJOL)

The samples were used for haematological and parasitological analyses and determination of serum concentrations of total cholesterol, triglycerides, high density lipoprotein-cholesterol (HDL-cholesterol) and low density lipoproteincholesterol (LDL-cholesterol). All animals in the infected group showed parasitaemia by day ...

The effects of coconut oil supplementation on the body composition and lipid profile of rats submitted to physical exercise

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NATHÁLIA M. RESENDE

2016-06-01

Full Text Available This study aims to verify the effects of coconut oil supplementation (COS in the body composition and lipid profile of rats submitted to physical exercise. The animals (n=6 per group were randomly assigned to: G1=Sedentary and Non-supplemented (Control Group, G2=Sedentary and Supplemented, G3=Exercised and Non-supplemented and G4=Exercised and Supplemented. The COS protocol used was 3 mL/Kg of body mass by gavage for 28 days. The physical exercise was the vertical jumping training for 28 days. It was determined the body mass parameters, Lee Index, blood glucose and lipid profile. The COS did not interfere with body mass, but the lean body mass was lower in G3 compared to G2. The final Lee Index classified G1 and G2 as obese (>30g/cm. The lipid profile showed total cholesterol was decreased in G3, LDL-c concentration was decreased in G2, triglycerides, VLDL-c and HDL-c concentrations were increased in G2 and G4 in relation to G1 and G3. The COS decreased LDL-c/HDL-c ratio. In conclusion, the COS associated or not to physical exercise worsen others lipid parameters, like triglycerides and VLDL-c level, showing the care with the use of lipid supplements.

The Role of Macrophage Lipophagy in Reverse Cholesterol Transport

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Se-Jin Jeong

2017-03-01

Full Text Available Macrophage cholesterol efflux is a central step in reverse cholesterol transport, which helps to maintain cholesterol homeostasis and to reduce atherosclerosis. Lipophagy has recently been identified as a new step in cholesterol ester hydrolysis that regulates cholesterol efflux, since it mobilizes cholesterol from lipid droplets of macrophages via autophagy and lysosomes. In this review, we briefly discuss recent advances regarding the mechanisms of the cholesterol efflux pathway in macrophage foam cells, and present lipophagy as a therapeutic target in the treatment of atherosclerosis.

Effects of thiosulfonates on the lipid composition of rat tissues

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A. Z. Pylypets

2017-12-01

Full Text Available Thiosulfonates are synthetic analogs of organic sulfur-containing compounds isolated from plants. Recent studies have shown that these substances lowering cholesterol content in the body, are effective against hyperlipidemia. Therefore, the aim of our investigation was to study the effect of synthesized thiosulfonates on the content of lipids and their spectrum in rats blood, liver and kidney. The amount of total lipids and their fractional profile were determined by thin-layer chromatography. The administration of methyl-, ethyl-, and allylthiosulfonates at a dose of 300 mg/kg of body weight did not cause significant changes in the content of total lipids and phospholipids, but led to the redistribution of their classes in the examined tissues. The content of triacylglycerols in the blood plasma under the action of ethyl- and allylthiosulfonates was decreased by 29.14 and 23.19% (P < 0.05-0.01, respectively, whereas the injection with methyl- and ethylthiosulfonates was accompanied by a significant decrease in mono-, di-, triglycerides and free fatty acids in the liver compared to control. The most significant changes in the lipid profile of kidney tissue were detected under the action of methylthiosulfonate.

Lysosomal lipid storage diseases.

Science.gov (United States)

Schulze, Heike; Sandhoff, Konrad

2011-06-01

Lysosomal lipid storage diseases, or lipidoses, are inherited metabolic disorders in which typically lipids accumulate in cells and tissues. Complex lipids, such as glycosphingolipids, are constitutively degraded within the endolysosomal system by soluble hydrolytic enzymes with the help of lipid binding proteins in a sequential manner. Because of a functionally impaired hydrolase or auxiliary protein, their lipid substrates cannot be degraded, accumulate in the lysosome, and slowly spread to other intracellular membranes. In Niemann-Pick type C disease, cholesterol transport is impaired and unesterified cholesterol accumulates in the late endosome. In most lysosomal lipid storage diseases, the accumulation of one or few lipids leads to the coprecipitation of other hydrophobic substances in the endolysosomal system, such as lipids and proteins, causing a "traffic jam." This can impair lysosomal function, such as delivery of nutrients through the endolysosomal system, leading to a state of cellular starvation. Therapeutic approaches are currently restricted to mild forms of diseases with significant residual catabolic activities and without brain involvement.

Pollen viability and membrane lipid composition

NARCIS (Netherlands)

Bilsen, van D.G.J.L.

1993-01-01

In this thesis membrane lipid composition is studied in relation to pollen viability during storage. Chapter 1 reviews pollen viability, membranes in the dry state and membrane changes associated with cellular aging. This chapter is followed by a study of age-related changes in phospholipid

Danish Guidelines for Lipid-lowering Treatment in Patients with Chronic Renal Failure

DEFF Research Database (Denmark)

Dieperink, Hans; Christensen, Jeppe Hagstrup; Feldt-Rasmussen, Bo

2014-01-01

Measurement of lipid profile in adults with CKD 1-5: We recommend measuring the lipid profile (T cholesterol, LDL cholesterol, HDL cholesterol and triglycerides) in all adults with newly diagnosed CKD 1-5 (including patients in renal replacement therapy). Monitoring of lipid profile in adults wit...

Danish guidelines for lipid-lowering treatment in patients with chronic renal failure

DEFF Research Database (Denmark)

Dieperink, Hans; Christensen, Jeppe Hagstrup; Feldt-Rasmussen, Bo

2014-01-01

Measurement of lipid profile in adults with CKD 1-5: We recommend measuring the lipid profile (T cholesterol, LDL cholesterol, HDL cholesterol and triglycerides) in all adults with newly diagnosed CKD 1-5 (including patients in renal replacement therapy). Monitoring of lipid profile in adults wit...

Digital holographic microscopy of phase separation in multicomponent lipid membranes

Science.gov (United States)

Farzam Rad, Vahideh; Moradi, Ali-Reza; Darudi, Ahmad; Tayebi, Lobat

2016-12-01

Lateral in-homogeneities in lipid compositions cause microdomains formation and change in the physical properties of biological membranes. With the presence of cholesterol and mixed species of lipids, phospholipid membranes segregate into lateral domains of liquid-ordered and liquid-disordered phases. Coupling of two-dimensional intralayer phase separations and interlayer liquid-crystalline ordering in multicomponent membranes has been previously demonstrated. By the use of digital holographic microscopy (DHMicroscopy), we quantitatively analyzed the volumetric dynamical behavior of such membranes. The specimens are lipid mixtures composed of sphingomyelin, cholesterol, and unsaturated phospholipid, 1,2-dioleoyl-sn-glycero-3-phosphocholine. DHMicroscopy in a transmission mode is an effective tool for quantitative visualization of phase objects. By deriving the associated phase changes, three-dimensional information on the morphology variation of lipid stacks at arbitrary time scales is obtained. Moreover, the thickness distribution of the object at demanded axial planes can be obtained by numerical focusing. Our results show that the volume evolution of lipid domains follows approximately the same universal growth law of previously reported area evolution. However, the thickness of the domains does not alter significantly by time; therefore, the volume evolution is mostly attributed to the changes in area dynamics. These results might be useful in the field of membrane-based functional materials.

The Interpretation of Cholesterol Balance Derived Synthesis Data and Surrogate Noncholesterol Plasma Markers for Cholesterol Synthesis under Lipid Lowering Therapies

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Frans Stellaard

2017-01-01

Full Text Available The cholesterol balance procedure allows the calculation of cholesterol synthesis based on the assumption that loss of endogenous cholesterol via fecal excretion and bile acid synthesis is compensated by de novo synthesis. Under ezetimibe therapy hepatic cholesterol is diminished which can be compensated by hepatic de novo synthesis and hepatic extraction of plasma cholesterol. The plasma lathosterol concentration corrected for total cholesterol concentration (R_Lath as a marker of de novo cholesterol synthesis is increased during ezetimibe treatment but unchanged under treatment with ezetimibe and simvastatin. Cholesterol balance derived synthesis data increase during both therapies. We hypothesize the following. (1 The cholesterol balance data must be applied to the hepatobiliary cholesterol pool. (2 The calculated cholesterol synthesis value is the sum of hepatic de novo synthesis and the net plasma—liver cholesterol exchange rate. (3 The reduced rate of biliary cholesterol absorption is the major trigger for the regulation of hepatic cholesterol metabolism under ezetimibe treatment. Supportive experimental and literature data are presented that describe changes of cholesterol fluxes under ezetimibe, statin, and combined treatments in omnivores and vegans, link plasma R_Lath to liver function, and define hepatic de novo synthesis as target for regulation of synthesis. An ezetimibe dependent direct hepatic drug effect cannot be excluded.

Incorporation of photosenzitizer hypericin into synthetic lipid-based nano-particles for drug delivery and large unilamellar vesicles with different content of cholesterol

Science.gov (United States)

Joniova, Jaroslava; Blascakova, Ludmila; Jancura, Daniel; Nadova, Zuzana; Sureau, Franck; Miskovsky, Pavol

2014-08-01

Low-density lipoproteins (LDL) and high-density lipoproteins (HDL) are attractive natural occurring vehicles for drug delivery and targeting to cancer tissues. The capacity of both types of the lipoproteins to bind hydrophobic drugs and their functionality as drug carriers have been examined in several studies and it has been also shown that mixing of anticancer drugs with LDL or HDL before administration led to an increase of cytotoxic effects of the drugs in the comparison when the drugs were administered alone. However, a difficult isolation of the lipoproteins in large quantity from a biological organism as well as a variability of the composition and size of these molecules makes practical application of LDL and HDL as drug delivery systems quite complicated. Synthetic LDL and HDL and large unilamellar vesicles (LUV) are potentially suitable candidates to substitute the native lipoproteins for targeted and effective drug delivery. In this work, we have studied process of an association of potent photosensitizer hypericin (Hyp) with synthetic lipid-based nano-particles (sLNP) and large unilamellar vesicles (LUV) containing various amount of cholesterol. Cholesterol is one of the main components of both LDL and HDL particles and its presence in biological membranes is known to be a determining factor for membrane properties. It was found that the behavior of Hyp incorporation into sLNP particles with diameter ca ~ 90 nm is qualitatively very similar to that of Hyp incorporation into LDL (diameter ca. 22 nm) and these particles are able to enter U-87 MG cells by endocytosis. The presence of cholesterol in LUV influences the capacity of these vesicles to incorporate Hyp into their structure.

Effects of Yogurt Containing Fermented Pepper Juice on the Body Fat and Cholesterol Level in High Fat and High Cholesterol Diet Fed Rat.

Science.gov (United States)

Yeon, Su-Jung; Hong, Go-Eun; Kim, Chang-Kyu; Park, Woo Joon; Kim, Soo-Ki; Lee, Chi-Ho

2015-01-01

This experiment investigated whether yogurt containing fermented pepper juice (FPJY) affects cholesterol level in high fat and high cholesterol diet (HFCD) fed rat. Twenty five Sprague-Dawley male rats of 7 wk were divided into 5 groups, and fed following diets for 9 wk; CON (control diet), HFCD (HFCD), PY (HFCD supplemented with 2% of plain yogurt), LFY (HFCD supplemented with 2% of FPJY), and HFY (HFCD supplemented with 5% of FPJY). In the LFY group, hepatic total lipid level decreased significantly compared to the HFCD group (p0.05). In HFY group, body weight and hepatic total lipid level significantly decreased over the HFCD group (p0.05). Liver weight decreased as FPJY content was increased. Results suggested FPJY would inhibit organ hypertrophy and accumulation of body fat, hepatic lipid, and cholesterol in HFCD fed rat.

Effects of intermittent fasting and chronic swimming exercise on body composition and lipid metabolism.

Science.gov (United States)

Moraes, Ruan Carlos Macedo de; Portari, Guilherme Vannucchi; Ferraz, Alex Soares Marreiros; da Silva, Tiago Eugênio Oliveira; Marocolo, Moacir

2017-12-01

Intermittent fasting protocol (IFP) has been suggested as a strategy to change body metabolism and improve health. The effects of IFP seem to be similar to aerobic exercise, having a hormetic adaptation according to intensity and frequency. However, the effects of combining both interventions are still unknown. Therefore, the aim of the present study was to evaluate the effects of IFP with and without endurance-exercise training on body composition, food behavior, and lipid metabolism. Twenty-week-old Wistar rats were kept under an inverted circadian cycle of 12 h with water ad libitum and assigned to 4 different groups: control group (ad libitum feeding and sedentary), exercise group (ad libitum feeding and endurance training), intermittent fasting group (IF; intermittent fasting and sedentary), and intermittent fasting and exercise group (IFEX; intermittent fasting and endurance training). After 6 weeks, the body weight of IF and IFEX animals decreased without changes in food consumption. Yet, the body composition between the 2 groups was different, with the IFEX animals containing higher total protein and lower total fat content than the IF animals. The IFEX group also showed increases in total high-density lipoprotein cholesterol and increased intramuscular lipid content. The amount of brown adipose tissue was higher in IF and IFEX groups; however, the IFEX group showed higher expression levels of uncoupling protein 1 in this tissue, indicating a greater thermogenesis. The IFP combined with endurance training is an efficient method for decreasing body mass and altering fat metabolism, without inflicting losses in protein content.

Effects of dietary yeast autolysate (Saccharomyces cerevisiae) on performance, egg traits, egg cholesterol content, egg yolk fatty acid composition and humoral immune response of laying hens.

Science.gov (United States)

Yalçin, Sakine; Yalçin, Suzan; Cakin, Kemal; Eltan, Onder; Dağaşan, Levent

2010-08-15

The objective of this study was to determine the effects of dietary yeast autolysate on performance, egg traits, egg cholesterol content, egg yolk fatty acid composition, lipid oxidation of egg yolk, some blood parameters and humoral immune response of laying hens during a 16 week period. A total of 225 Hyline Brown laying hens, 22 weeks of age, were allocated equally to one control group and four treatment groups. Yeast autolysate (Saccharomyces cerevisiae, InteWall) was used at levels of 1, 2, 3 and 4 g kg(-1) in the diets of the first, second, third and fourth treatment groups respectively. Dietary treatments did not significantly affect body weight, feed intake and egg traits. Yeast autolysate supplementation increased egg production (P Yeast autolysate at levels of 2, 3 and 4 g kg(-1) decreased egg yolk cholesterol level as mg g(-1) yolk (P yeast autolysate supplementation. Dietary yeast autolysate at levels of 2, 3 and 4 g kg(-1) had beneficial effects on performance, egg cholesterol content and humoral immune response. It is concluded that 2 g kg(-1) yeast autolysate will be enough to have beneficial effects in laying hens. Copyright (c) 2010 Society of Chemical Industry.

Morphology and Molecular Composition of Purified Bovine Viral Diarrhea Virus Envelope.

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Nathalie Callens

2016-03-01

Full Text Available The family Flaviviridae includes viruses that have different virion structures and morphogenesis mechanisms. Most cellular and molecular studies have been so far performed with viruses of the Hepacivirus and Flavivirus genera. Here, we studied bovine viral diarrhea virus (BVDV, a member of the Pestivirus genus. We set up a method to purify BVDV virions and analyzed their morphology by electron microscopy and their protein and lipid composition by mass spectrometry. Cryo-electron microscopy showed near spherical viral particles displaying an electron-dense capsid surrounded by a phospholipid bilayer with no visible spikes. Most particles had a diameter of 50 nm and about 2% were larger with a diameter of up to 65 nm, suggesting some size flexibility during BVDV morphogenesis. Morphological and biochemical data suggested a low envelope glycoprotein content of BVDV particles, E1 and E2 being apparently less abundant than Erns. Lipid content of BVDV particles displayed a ~2.3 to 3.5-fold enrichment in cholesterol, sphingomyelin and hexosyl-ceramide, concomitant with a 1.5 to 5-fold reduction of all glycerophospholipid classes, as compared to lipid content of MDBK cells. Although BVDV buds in the endoplasmic reticulum, its lipid content differs from a typical endoplasmic reticulum membrane composition. This suggests that BVDV morphogenesis includes a mechanism of lipid sorting. Functional analyses confirmed the importance of cholesterol and sphingomyelin for BVDV entry. Surprisingly, despite a high cholesterol and sphingolipid content of BVDV envelope, E2 was not found in detergent-resistant membranes. Our results indicate that there are differences between the structure and molecular composition of viral particles of Flaviviruses, Pestiviruses and Hepaciviruses within the Flaviviridae family.

Lipid Parameters in Patients with Polycystic Ovary Syndrome

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Cristian Ioan IUHAS

2012-11-01

Full Text Available The purpose of our study was to investigate the lipid profile in patients with polycystic ovary syndrome (PCOS. Methods: a retrospective review of the medical records of female patients addressing for a consultation in a private healthcare network in Cluj-Napoca between 2009 and 2011 was performed. Patients with complete lipid profile and without previous treatment were included in the PCOS group. PCOS was diagnosed using Rotterdam criteria for PCOS. Healthy female patients matched for age but without PCOS were included in the control group. Results: Compared with healthy women, women with PCOS presented higher total cholesterol levels (mean difference = 27.5 mg/dl for total cholesterol, p = 0.004 and LDL-cholesterol (mean difference = 38.1 mg/dl, p < 0.001. HDL-cholesterol displayed lower levels in PCOS patients compared with healthy women (44.4±12.2 mg/dl vs. 50.5±12.2 mg/dl, p = 0.02. No difference was observed between groups in terms of triglycerides levels. In regression analysis both total cholesterol and LDL-cholesterol were positively associated only with the presence of PCOS (β = 0.30, p = 0.01 for total cholesterol, β = 0.44, p<0.001 for LDL-cholesterol. No association was observed between HDL-cholesterol levels and the presence of PCOS. Conclusion: The results of our study show that women with PCOS have altered lipid profile, with higher cholesterol levels (both total and LDL and lower HDL cholesterol compared with healthy women. These lipid parameters were associated with the presence of PCOS and not with parameters describing body weight.

Lipid Raft: A Floating Island Of Death or Survival

Science.gov (United States)

George, Kimberly S.; Wu, Shiyong

2012-01-01

Lipid rafts are microdomains of the plasma membrane enriched in cholesterol and sphingolipids, and play an important role in the initiation of many pharmacological agent-induced signaling pathways and toxicological effects. The structure of lipid rafts is dynamic, resulting in an ever-changing content of both lipids and proteins. Cholesterol, as a major component of lipid rafts, is critical for the formation and configuration of lipid rafts microdomains, which provide signaling platforms capable of activating both pro-apoptotic and anti-apoptotic signaling pathways. A change of cholesterol level can result in lipid rafts disruption and activate or deactivate raft-associated proteins, such as death receptor proteins, protein kinases, and calcium channels. Several anti-cancer drugs are able to suppress growth and induce apoptosis of tumor cells through alteration of lipid raft contents via disrupting lipid raft integrity. PMID:22289360

Mesoscale organization of domains in the plasma membrane - beyond the lipid raft.

Science.gov (United States)

Lu, Stella M; Fairn, Gregory D

2018-04-01

The plasma membrane is compartmentalized into several distinct regions or domains, which show a broad diversity in both size and lifetime. The segregation of lipids and membrane proteins is thought to be driven by the lipid composition itself, lipid-protein interactions and diffusional barriers. With regards to the lipid composition, the immiscibility of certain classes of lipids underlies the "lipid raft" concept of plasmalemmal compartmentalization. Historically, lipid rafts have been described as cholesterol and (glyco)sphingolipid-rich regions of the plasma membrane that exist as a liquid-ordered phase that are resistant to extraction with non-ionic detergents. Over the years the interest in lipid rafts grew as did the challenges with studying these nanodomains. The term lipid raft has fallen out of favor with many scientists and instead the terms "membrane raft" or "membrane nanodomain" are preferred as they connote the heterogeneity and dynamic nature of the lipid-protein assemblies. In this article, we will discuss the classical lipid raft hypothesis and its limitations. This review will also discuss alternative models of lipid-protein interactions, annular lipid shells, and larger membrane clusters. We will also discuss the mesoscale organization of plasmalemmal domains including visible structures such as clathrin-coated pits and caveolae.

Recognition of Odontogenic Cyst-Fluid Cholesterol Concentration ...

African Journals Online (AJOL)

Background: Hypercholesterolaemia is a risk factor for cardiovascular diseases. Serum cholesterol is usually determined to know if a subject is at a risk of heart diseases. This lipid is found in most fluids in the body including the odontogenic cyst-fluid. We investigated the concentration of cholesterol in the odontogenic ...

Whole-grain and blood lipid changes in apparently healthy adults

DEFF Research Database (Denmark)

Hollænder, Pernille Lærke Bjørndal; Ross, Alastair B; Kristensen, Mette Bredal

2015-01-01

BACKGROUND: Whole grains are recognized for their potential role in preventing cardiovascular diseases; however, results from randomized controlled studies on blood lipids are inconsistent, potentially because of compositional differences between individual grain types for some nutrients, including...... dietary fiber. OBJECTIVE: Using a meta-analytic approach, we assessed the effect of whole-grain compared with non-whole-grain foods on changes in total cholesterol (TC), LDL cholesterol, HDL cholesterol, and triglycerides. DESIGN: We conducted a systematic literature search in selected databases. Studies...... were included if they were randomized controlled comparisons between whole-grain foods and a non-whole-grain control in adults. A total of 6069 articles were screened for eligibility, and data were extracted from 24 studies. Weighted mean differences were calculated, and meta-regression analyses were...

Cholesterol-raising diterpenes in types of coffee commonly consumed in Singapore, Indonesia and India and associations with blood lipids: a survey and cross sectional study.

Science.gov (United States)

Naidoo, Nasheen; Chen, Cynthia; Rebello, Salome A; Speer, Karl; Tai, E Shyong; Lee, Jeanette; Buchmann, Sandra; Koelling-Speer, Isabelle; van Dam, Rob M

2011-05-15

To measure the content of cholesterol-raising diterpenes in coffee sold at the retailer level in Singapore, Indonesia and India and to determine the relationship of coffee consumption with lipid levels in a population-based study in Singapore. Survey and cross-sectional study in local coffee shops in Singapore, Indonesia and India to measure the diterpene content in coffee, and a population-based study in Singapore to examine the relationship of coffee consumption and blood lipid levels. Interviews and coffee samples (n=27) were collected from coffee shops in Singapore, Indonesia and India. In addition, 3000 men and women who were Chinese, Malay, and Indian residents of Singapore participated in a cross-sectional study. The traditional 'sock' method of coffee preparation used in Singapore resulted in cafestol concentrations comparable to European paper drip filtered coffee (mean 0.09±SD 0.064 mg/cup). This amount would result in negligible predicted increases in serum cholesterol and triglyceride concentrations. Similarly low amounts of cafestol were found in Indian 'filter' coffee that used a metal mesh filter (0.05±0.05 mg/cup). Coffee samples from Indonesia using the 'sock' method (0.85±0.41 mg/cup) or a metal mesh filter (0.98 mg/cup) contained higher amounts of cafestol comparable to espresso coffee. Unfiltered coffee from Indonesia contained an amount of cafestol (4.43 mg/cup) similar to Scandinavian boiled, Turkish and French press coffee with substantial predicted increases in serum cholesterol (0.33 mmol/l) and triglycerides (0.20 mmol/l) concentrations for consumption of 5 cups per day. In the Singaporean population, higher coffee consumption was not substantially associated with serum lipid concentrations after adjustment for potential confounders [LDL-cholesterol: 3.07 (95% confidence interval 2.97-3.18) for Singapore and India, coffee consumption in these countries does not appear to be a risk factor for elevation of serum cholesterol, whereas

Effects of plant sterol esters in skimmed milk and vegetable-fat-enriched milk on serum lipids and non-cholesterol sterols in hypercholesterolaemic subjects: a randomised, placebo-controlled, crossover study.

Science.gov (United States)

Casas-Agustench, Patricia; Serra, Mercè; Pérez-Heras, Ana; Cofán, Montserrat; Pintó, Xavier; Trautwein, Elke A; Ros, Emilio

2012-06-01

Plant sterol (PS)-supplemented foods are recommended to help in lowering serum LDL-cholesterol (LDL-C). Few studies have examined the efficacy of PS-enriched skimmed milk (SM) or semi-SM enriched with vegetable fat (PS-VFM). There is also insufficient information on factors predictive of LDL-C responses to PS. We examined the effects of PS-SM (0·1 % dairy fat) and PS-VFM (0·1 % dairy fat plus 1·5 % vegetable fat) on serum lipids and non-cholesterol sterols in hypercholesterolaemic individuals. In a placebo-controlled, crossover study, forty-three subjects with LDL-C>1300 mg/l were randomly assigned to three 4-week treatment periods: control SM, PS-SM and PS-VFM, with 500 ml milk with or without 3·4 g PS esters (2 g free PS). Serum concentrations of lipids and non-cholesterol sterols were measured. Compared to control, LDL-C decreased by 8·0 and 7·4 % (P synthesis and high cholesterol absorption predicted improved LDL-C responses to PS.

Comparison of serum lipid profile in ischaemic and haemorrhagic stroke

International Nuclear Information System (INIS)

Mehmood, A.; Sharif, M.A.

2010-01-01

To compare serum lipid profile between patients of ischaemic and haemorrhagic strokes. Study Design: Cross sectional, comparative study. Place and Duration of Study: Military Hospital, Rawalpindi, from August 2004 to February 2005. Methodology: Patients with diagnosis of stroke comprising 100 consecutive patients each of ischaemic and haemorrhagic strokes were included in the study while patients on lipid lowering therapy were excluded from study. To determine the subtype of stroke, clinical examination followed by CT scan of brain was done. A serum sample after 8 hours of overnight fasting was taken on the next day of admission for both groups of patients. Total serum cholesterol, triglycerides, LDL cholesterol, VLDL-cholesterol and HDL-cholesterol was determined, using enzymatic colorimetric method. Statistical analysis was done by comparison of lipid profile in two subgroups, using proportion test for any significant difference. Results: The mean age at presentation of patients with stroke was 64.2+-12 years with a male to female ratio of 3.6:1. In 100 ischaemic stroke patients, raised serum total cholesterol was seen in 42, triglyceride in 04, LDL-cholesterol in 05 and VLDL-cholesterol in 07 patients. Serum HDL-cholesterol was below the normal reference in 31 cases. On the other hand, serum total cholesterol and triglycerides was raised in 05 patients each, LDL-cholesterol in 09 and VLDL-cholesterol in 03 patients of haemorrhagic stroke. Serum HDL-cholesterol was below normal in 04 patients of haemorrhagic stroke. On comparison, there were significantly greater number of patients with raised serum cholesterol and low HDL-cholesterol in ischaemic stroke than haemorrhagic stroke (p < 0.05). No statistical significance was found on comparing serum values of ischaemic and haemorrhagic stroke for triglycerides, LDL-cholesterol and VLDL-cholesterol. Conclusion: Ischaemic stroke patients had high serum total cholesterol and lower HDL-cholesterol levels as compared to

Cholesterol regulates the endoplasmic reticulum exit of the major membrane protein P0 required for peripheral myelin compaction.

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Saher, Gesine; Quintes, Susanne; Möbius, Wiebke; Wehr, Michael C; Krämer-Albers, Eva-Maria; Brügger, Britta; Nave, Klaus-Armin

2009-05-13

Rapid impulse conduction requires electrical insulation of axons by myelin, a cholesterol-rich extension of the glial cell membrane with a characteristic composition of proteins and lipids. Mutations in several myelin protein genes cause endoplasmic reticulum (ER) retention and disease, presumably attributable to failure of misfolded proteins to pass the ER quality control. Because many myelin proteins partition into cholesterol-rich membrane rafts, their interaction with cholesterol could potentially be part of the ER quality control system. Here, we provide in vitro and in vivo evidence that the major peripheral myelin protein P0 requires cholesterol for exiting the ER and reaching the myelin compartment. Cholesterol dependency of P0 trafficking in heterologous cells is mediated by a cholesterol recognition/interaction amino acid consensus (CRAC) motif. Mutant mice lacking cholesterol biosynthesis in Schwann cells suffer from severe hypomyelination with numerous uncompacted myelin stretches. This demonstrates that high-level cholesterol coordinates P0 export with myelin membrane synthesis, which is required for the correct stoichiometry of myelin components and for myelin compaction.

Terminalia pallida fruit ethanolic extract ameliorates lipids, lipoproteins, lipid metabolism marker enzymes and paraoxonase in isoproterenol-induced myocardial infarcted rats

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Althaf Hussain Shaik

2018-03-01

Full Text Available The present study aimed to evaluate the effect of Terminalia pallida fruit ethanolic extract (TpFE on lipids, lipoproteins, lipid metabolism marker enzymes and paraoxonase (PON in isoproterenol (ISO-induced myocardial infarcted rats. PON is an excellent serum antioxidant enzyme which involves in the protection of low density lipoprotein cholesterol (LDL-C from the process of oxidation for the prevention of cardiovascular diseases. ISO caused a significant increase in the concentration of total cholesterol, triglycerides, LDL-C, very low density lipoprotein cholesterol and lipid peroxidation whereas significant decrease in the concentration of high density lipoprotein cholesterol. ISO administration also significantly decreased the activities of lecithin cholesterol acyl transferase, PON and lipoprotein lipase whereas significantly increased the activity of 3-hydroxy-3-methylglutaryl-coenzyme-A reductase. Oral pretreatment of TpFE at doses 100, 300 and 500 mg/kg body weight (bw and gallic acid (15 mg/kg bw for 30 days challenged with concurrent injection of ISO (85 mg/kg bw on 29th and 30th day significantly attenuated these alterations and restored the levels of lipids, lipoproteins and the activities of lipid metabolizing enzymes. Also TpFE significantly elevated the serum antioxidant enzyme PON. This is the first report revealed that pretreatment with TPFE ameliorated lipid metabolic marker enzymes and increased the antioxidant PON in ISO treated male albino Wistar rats. Keywords: Terminalia pallida fruit, Gallic acid, Isoproterenol, Lipid metabolism marker enzymes, Paraoxonase, Myocardial infarction

Serum lipid profile changes after successful treatment with electroconvulsive therapy in major depression: A prospective pilot trial.

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Aksay, Suna Su; Bumb, Jan Malte; Janke, Christoph; Biemann, Ronald; Borucki, Katrin; Lederbogen, Florian; Deuschle, Michael; Sartorius, Alexander; Kranaster, Laura

2016-01-01

Cholesterol is reduced in depressed patients, however, these patients have a higher risk for cardiovascular diseases. Electroconvulsive therapy (ECT) is a highly effective treatment option for specific forms of depression. Like for other non-pharmacological therapies targeting depression such as psychotherapy or sleep deprivation, there is a lack of evidence about the effects on peripheral lipid parameters. Our objective was to study the impact of ECT as a non-pharmacological treatment on the peripheral lipid pattern in depressive patients. Peripheral lipid profile composition before and after a course of ECT was analysed in 27 non-fasting inpatients at a university psychiatric hospital with DSM-IV major depressive episode. For the impact of ECT treatment on each lipid parameter a multivariate repeated measurement regression analysis was performed and computed separately for every dependent variable. Total Cholesterol and the cholesterol subtypes HDL and LDL were increased after the treatment compared to baseline. Apolipoprotein A1 was also increased after ECT, whereas apolipoprotein B was not. Indices for the prediction of cardiovascular diseases were unchanged after successful treatment by ECT. The reduction of depressive psychopathology negatively correlated with increases of HDL cholesterol and apolipoprotein A1. Subjects received several antidepressants and other psychotropic medication before and during the ECT. In our preliminary pilot study ECT as a non-pharmacological, effective treatment of depression led to distinct effects on the peripheral lipid pattern. Copyright © 2015 Elsevier B.V. All rights reserved.

Impact of two different saponins on the organization of model lipid membranes.

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Korchowiec, Beata; Gorczyca, Marcelina; Wojszko, Kamila; Janikowska, Maria; Henry, Max; Rogalska, Ewa

2015-10-01

Saponins, naturally occurring plant compounds are known for their biological and pharmacological activity. This activity is strongly related to the amphiphilic character of saponins that allows them to aggregate in aqueous solution and interact with membrane components. In this work, Langmuir monolayer techniques combined with polarization modulation infrared reflection-absorption spectroscopy (PM-IRRAS) and Brewster angle microscopy were used to study the interaction of selected saponins with lipid model membranes. Two structurally different saponins were used: digitonin and a commercial Merck Saponin. Membranes of different composition, namely, cholesterol, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine or 1,2-dipalmitoyl-sn-glycero-3-phospho-rac-(1-glycerol) were formed at the air/water and air/saponin solution interfaces. The saponin-lipid interaction was characterized by changes in surface pressure, surface potential, surface morphology and PM-IRRAS signal. Both saponins interact with model membranes and change the physical state of membranes by perturbing the lipid acyl chain orientation. The changes in membrane fluidity were more significant upon the interaction with Merck Saponin. A higher affinity of saponins for cholesterol than phosphatidylglycerols was observed. Moreover, our results indicate that digitonin interacts strongly with cholesterol and solubilize the cholesterol monolayer at higher surface pressures. It was shown, that digitonin easily penetrate to the cholesterol monolayer and forms a hydrogen bond with the hydroxyl groups. These findings might be useful in further understanding of the saponin action at the membrane interface and of the mechanism of membrane lysis. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of cholesterol nucleation-promoting activity on cholesterol solubilization in model bile

NARCIS (Netherlands)

Groen, A. K.; Ottenhoff, R.; Jansen, P. L.; van Marle, J.; Tytgat, G. N.

1989-01-01

Human bile contains a factor with cholesterol nucleation-promoting activity that binds to concanavalin A-Sepharose. In this study we have investigated the effect of this activity on the dynamics of lipid solubilization in supersaturated model bile. A concanavalin A binding protein fraction of human

A systematic review and meta-analysis of randomized controlled trials of the effect of konjac glucomannan, a viscous soluble fiber, on LDL cholesterol and the new lipid targets non-HDL cholesterol and apolipoprotein B.

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Ho, Hoang Vi Thanh; Jovanovski, Elena; Zurbau, Andreea; Blanco Mejia, Sonia; Sievenpiper, John L; Au-Yeung, Fei; Jenkins, Alexandra L; Duvnjak, Lea; Leiter, Lawrence; Vuksan, Vladimir

2017-05-01

Background: Evidence from randomized controlled trials (RCTs) suggests the consumption of konjac glucomannan (KJM), a viscous soluble fiber, for improving LDL-cholesterol concentrations. It has also been suggested that the cholesterol-lowering potential of KJM may be greater than that of other fibers. However, trials have been relatively scarce and limited in sample size and duration, and the effect estimates have been inconsistent. The effect of KJM on new lipid targets of cardiovascular disease (CVD) risk is also unknown. Objective: This systematic review and meta-analysis aimed to assess the effect of KJM on LDL cholesterol, non-HDL cholesterol, and apolipoprotein B. Design: Medline, Embase, CINAHL, and the Cochrane Central databases were searched. We included RCTs with a follow-up of ≥3 wk that assessed the effect of KJM on LDL cholesterol, non-HDL cholesterol, or apolipoprotein B. Data were pooled by using the generic inverse-variance method with random-effects models and expressed as mean differences (MDs) with 95% CIs. Heterogeneity was assessed by the Cochran Q statistic and quantified by the I 2 statistic. Results: Twelve studies ( n = 370), 8 in adults and 4 in children, met the inclusion criteria. KJM significantly lowered LDL cholesterol (MD: -0.35 mmol/L; 95% CI: -0.46, -0.25 mmol/L) and non-HDL cholesterol (MD: -0.32 mmol/L; 95% CI: -0.46, -0.19 mmol/L). Data from 6 trials suggested no impact of KJM on apolipoprotein B. Conclusions: Our findings support the intake of ∼3 g KJM/d for reductions in LDL cholesterol and non-HDL cholesterol of 10% and 7%, respectively. The information may be of interest to health agencies in crafting future dietary recommendations related to reduction in CVD risk. This study was registered at clinicaltrials.gov as NCT02068248. © 2017 American Society for Nutrition.

Complexation of phospholipids and cholesterol by triterpenic saponins in bulk and in monolayers.

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Wojciechowski, Kamil; Orczyk, Marta; Gutberlet, Thomas; Geue, Thomas

2016-02-01

The interactions between three triterpene saponins: α-hederin, hederacoside C and ammonium glycyrrhizate with model lipids: cholesterol and dipalmitoylphosphatidylcholine (DPPC) are described. The oleanolic acid-type saponins (α-hederin and hederacoside C) were shown to form 1:1 complexes with lipids in bulk, characterized by stability constants in the range (4.0±0.2)·10(3)-(5.0±0.4)·10(4) M(-1). The complexes with cholesterol are generally stronger than those with DPPC. On the contrary, ammonium glycyrrhizate does not form complexes with any of the lipids in solution. The saponin-lipid interactions were also studied in a confined environment of Langmuir monolayers of DPPC and DPPC/cholesterol with the saponins present in the subphase. A combined monolayer relaxation, surface dilational rheology, fluorescence microscopy and neutron reflectivity (NR) study showed that all three saponins are able to penetrate pure DPPC and mixed DPPC/cholesterol monolayers. Overall, the effect of the saponins on the model lipid monolayers does not fully correlate with the lipid-saponin complex formation in the homogeneous solution. The best correlation was found for α-hederin, for which even the preference for cholesterol over DPPC observed in bulk is well reflected in the monolayer studies and the literature data on its membranolytic activity. Similarly, the lack of interaction of ammonium glycyrrhizate with both lipids is evident equally in bulk and monolayer experiments, as well as in its weak membranolytic activity. The combined bulk and monolayer results are discussed in view of the role of confinement in modulating the saponin-lipid interactions and possible mechanism of membranolytic activity of saponins. Copyright © 2015 Elsevier B.V. All rights reserved.

2H NMR evidence for antibiotic-induced cholesterol immobilization in biological model membranes

International Nuclear Information System (INIS)

Dufourc, E.J.; Smith, I.C.

1985-01-01

The interaction of the polyene antibiotic filipin with membrane sterols has been studied by deuterium nuclear magnetic resonance of the molecular probes [2,2,3,4,4,6- 2 H6]cholesterol and 1-myristoyl-2-[4',4',14',14',14'- 2 H5]myristoyl-sn-glycero-3-phospho- choline. At physiological temperatures, there is evidence of filipin-induced cholesterol immobilization in the membrane. The 2 H NMR spectra of cholesterol show two domains in which ordering and dynamics are very different. In one of these, cholesterol is static on the 2 H NMR time scale, whereas in the other it undergoes rapid axially symmetric motions similar to those it exhibits in the drug-free membrane; this indicates that the jumping frequency of cholesterol between the labile and immobilized domains is less than 10(5) s -1 . The distribution of cholesterol between these two sites is temperature dependent. In contrast to cholesterol, the phospholipids sense only one type of environment, at both the top and center of the bilayer, indicating that cholesterol acts as a screen, preventing the lipids from direct interaction with the antibiotic. At low temperature, the ordering of the lipid in the presence of cholesterol does not change upon filipin addition, whereas at elevated temperatures the local ordering of both the lipid and the labile cholesterol is significantly lower than that in the absence of the drug

Differential effect of corn oil-based low trans structured fat on the plasma and hepatic lipid profile in an atherogenic mouse model: comparison to hydrogenated trans fat

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Kim Hye-Jin

2011-01-01

Full Text Available Abstract Background Trans fat are not desirable in many aspects on health maintenance. Low trans structured fats have been reported to be relatively more safe than trans fats. Methods We examined the effects of low trans structured fat from corn oil (LC, compared with high trans fat shortening, on cholesterol and fatty acid metabolism in apo E deficient mice which is an atherogenic animal model. The animals were fed a high trans fat (10% fat: commercial shortening (CS or a low trans fat (LC diet for 12 weeks. Results LC decreased apo B and hepatic cholesterol and triglyceride concentration compared to the CS group but significantly increased plasma total cholesterol and triglyceride concentration and fecal lipids with a simultaneous increase in HDL-cholesterol level, apo A-I, and the ratio of HDL-cholesterol to total cholesterol (HTR. Reduction of hepatic lipid levels by inclusion of LC intake was observed alongside modulation of hepatic enzyme activities related to cholesterol esterification, fatty acid metabolism and fecal lipids level compared to the CS group. The differential effects of LC intake on the plasma and hepatic lipid profile seemed to be partly due to the fatty acid composition of LC which contains higher MUFA, PUFA and SFA content as well as lower content of trans fatty acids compared to CS. Conclusions We suggest that LC may exert a dual effect on plasma and hepatic lipid metabolism in an atherogenic animal model. Accordingly, LC, supplemented at 10% in diet, had an anti-atherogenic effect on these apo E-/- mice, and increased fecal lipids, decreased hepatic steatosis, but elevated plasma lipids. Further studies are needed to verify the exact mode of action regarding the complex physiological changes and alteration in lipid metabolism caused by LC.

Differential effect of corn oil-based low trans structured fat on the plasma and hepatic lipid profile in an atherogenic mouse model: comparison to hydrogenated trans fat

Science.gov (United States)

2011-01-01

Background Trans fat are not desirable in many aspects on health maintenance. Low trans structured fats have been reported to be relatively more safe than trans fats. Methods We examined the effects of low trans structured fat from corn oil (LC), compared with high trans fat shortening, on cholesterol and fatty acid metabolism in apo E deficient mice which is an atherogenic animal model. The animals were fed a high trans fat (10% fat: commercial shortening (CS)) or a low trans fat (LC) diet for 12 weeks. Results LC decreased apo B and hepatic cholesterol and triglyceride concentration compared to the CS group but significantly increased plasma total cholesterol and triglyceride concentration and fecal lipids with a simultaneous increase in HDL-cholesterol level, apo A-I, and the ratio of HDL-cholesterol to total cholesterol (HTR). Reduction of hepatic lipid levels by inclusion of LC intake was observed alongside modulation of hepatic enzyme activities related to cholesterol esterification, fatty acid metabolism and fecal lipids level compared to the CS group. The differential effects of LC intake on the plasma and hepatic lipid profile seemed to be partly due to the fatty acid composition of LC which contains higher MUFA, PUFA and SFA content as well as lower content of trans fatty acids compared to CS. Conclusions We suggest that LC may exert a dual effect on plasma and hepatic lipid metabolism in an atherogenic animal model. Accordingly, LC, supplemented at 10% in diet, had an anti-atherogenic effect on these apo E-/- mice, and increased fecal lipids, decreased hepatic steatosis, but elevated plasma lipids. Further studies are needed to verify the exact mode of action regarding the complex physiological changes and alteration in lipid metabolism caused by LC. PMID:21247503

Cholesterol Balance in Prion Diseases and Alzheimer’s Disease

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Hannaoui, Samia; Shim, Su Yeon; Cheng, Yo Ching; Corda, Erica; Gilch, Sabine

2014-01-01

Prion diseases are transmissible and fatal neurodegenerative disorders of humans and animals. They are characterized by the accumulation of PrPSc, an aberrantly folded isoform of the cellular prion protein PrPC, in the brains of affected individuals. PrPC is a cell surface glycoprotein attached to the outer leaflet of the plasma membrane by a glycosyl-phosphatidyl-inositol (GPI) anchor. Specifically, it is associated with lipid rafts, membrane microdomains enriched in cholesterol and sphinoglipids. It has been established that inhibition of endogenous cholesterol synthesis disturbs lipid raft association of PrPC and prevents PrPSc accumulation in neuronal cells. Additionally, prion conversion is reduced upon interference with cellular cholesterol uptake, endosomal export, or complexation at the plasma membrane. Altogether, these results demonstrate on the one hand the importance of cholesterol for prion propagation. On the other hand, growing evidence suggests that prion infection modulates neuronal cholesterol metabolism. Similar results were reported in Alzheimer’s disease (AD): whereas amyloid β peptide formation is influenced by cellular cholesterol, levels of cholesterol in the brains of affected individuals increase during the clinical course of the disease. In this review, we summarize commonalities of alterations in cholesterol homeostasis and discuss consequences for neuronal function and therapy of prion diseases and AD. PMID:25419621

Cholesterol Balance in Prion Diseases and Alzheimer’s Disease

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Samia Hannaoui

2014-11-01

Full Text Available Prion diseases are transmissible and fatal neurodegenerative disorders of humans and animals. They are characterized by the accumulation of PrPSc, an aberrantly folded isoform of the cellular prion protein PrPC, in the brains of affected individuals. PrPC is a cell surface glycoprotein attached to the outer leaflet of the plasma membrane by a glycosyl-phosphatidyl-inositol (GPI anchor. Specifically, it is associated with lipid rafts, membrane microdomains enriched in cholesterol and sphinoglipids. It has been established that inhibition of endogenous cholesterol synthesis disturbs lipid raft association of PrPC and prevents PrPSc accumulation in neuronal cells. Additionally, prion conversion is reduced upon interference with cellular cholesterol uptake, endosomal export, or complexation at the plasma membrane. Altogether, these results demonstrate on the one hand the importance of cholesterol for prion propagation. On the other hand, growing evidence suggests that prion infection modulates neuronal cholesterol metabolism. Similar results were reported in Alzheimer’s disease (AD: whereas amyloid β peptide formation is influenced by cellular cholesterol, levels of cholesterol in the brains of affected individuals increase during the clinical course of the disease. In this review, we summarize commonalities of alterations in cholesterol homeostasis and discuss consequences for neuronal function and therapy of prion diseases and AD.

Cholesterol and related sterols autoxidation.

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Zerbinati, Chiara; Iuliano, Luigi

2017-10-01

Cholesterol is a unique lipid molecule providing the building block for membranes, hormones, vitamin D and bile acid synthesis. Metabolism of cholesterol involves several enzymes acting on the sterol nucleus or the isooctyl tail. In the recent years, research interest has been focused on oxysterols, cholesterol derivatives generated by the addition of oxygen to the cholesterol backbone. Oxysterols can be produced enzymatically or by autoxidation. Autoxidation of cholesterol proceeds through type I or type II mechanisms. Type I autoxidation is initiated by free radical species, such as those arising from the superoxide/hydrogen peroxide/hydroxyl radical system. Type II autoxidation occurs stoichiometrically by non-radical highly reactive oxygen species such as singlet oxygen, HOCl, and ozone. The vulnerability of cholesterol towards high reactive species has raised considerable interest for mechanistic studies and for the potential biological activity of oxysterols, as well as for the use of oxysterols as biomarkers for the non-invasive study of oxidative stress in vivo. Copyright © 2017. Published by Elsevier Inc.

Increased membrane cholesterol in lymphocytes diverts T-cells toward an inflammatory response.

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Jacqueline Surls

Full Text Available Cell signaling for T-cell growth, differentiation, and apoptosis is initiated in the cholesterol-rich microdomains of the plasma membrane known as lipid rafts. Herein, we investigated whether enrichment of membrane cholesterol in lipid rafts affects antigen-specific CD4 T-helper cell functions. Enrichment of membrane cholesterol by 40-50% following squalene administration in mice was paralleled by an increased number of resting CD4 T helper cells in periphery. We also observed sensitization of the Th1 differentiation machinery through co-localization of IL-2Rα, IL-4Rα, and IL-12Rβ2 subunits with GM1 positive lipid rafts, and increased STAT-4 and STAT-5 phosphorylation following membrane cholesterol enrichment. Antigen stimulation or CD3/CD28 polyclonal stimulation of membrane cholesterol-enriched, resting CD4 T-cells followed a path of Th1 differentiation, which was more vigorous in the presence of increased IL-12 secretion by APCs enriched in membrane cholesterol. Enrichment of membrane cholesterol in antigen-specific, autoimmune Th1 cells fostered their organ-specific reactivity, as confirmed in an autoimmune mouse model for diabetes. However, membrane cholesterol enrichment in CD4(+Foxp3(+ T-reg cells did not alter their suppressogenic function. These findings revealed a differential regulatory effect of membrane cholesterol on the function of CD4 T-cell subsets. This first suggests that membrane cholesterol could be a new therapeutic target to modulate the immune functions, and second that increased membrane cholesterol in various physiopathological conditions may bias the immune system toward an inflammatory Th1 type response.

Fusion of raft-like lipid bilayers operated by a membranotropic domain of the HSV-type I glycoprotein gH occurs through a cholesterol-dependent mechanism.

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Vitiello, Giuseppe; Falanga, Annarita; Petruk, Ariel Alcides; Merlino, Antonello; Fragneto, Giovanna; Paduano, Luigi; Galdiero, Stefania; D'Errico, Gerardino

2015-04-21

A wealth of evidence indicates that lipid rafts are involved in the fusion of the viral lipid envelope with the target cell membrane. However, the interplay between these sterol- and sphingolipid-enriched ordered domains and viral fusion glycoproteins has not yet been clarified. In this work we investigate the molecular mechanism by which a membranotropic fragment of the glycoprotein gH of the Herpes Simplex Virus (HSV) type I (gH625) drives fusion of lipid bilayers formed by palmitoyl oleoyl phosphatidylcholine (POPC)-sphingomyelin (SM)-cholesterol (CHOL) (1 : 1 : 1 wt/wt/wt), focusing on the role played by each component. The comparative analysis of the liposome fusion assays, Dynamic Light Scattering (DLS), spectrofluorimetry, Neutron Reflectivity (NR) and Electron Spin Resonance (ESR) experiments, and Molecular Dynamics (MD) simulations shows that CHOL is fundamental for liposome fusion to occur. In detail, CHOL stabilizes the gH625-bilayer association by specific interactions with the peptide Trp residue. The interaction with gH625 causes an increased order of the lipid acyl chains, whose local rotational motion is significantly hampered. SM plays only a minor role in the process, favoring the propagation of lipid perturbation to the bilayer inner core. The stiffening of the peptide-interacting bilayer leaflet results in an asymmetric perturbation of the membrane, which is locally destabilized thus favoring fusion events. Our results show that viral fusion glycoproteins are optimally suited to exert a high fusogenic activity on lipid rafts and support the relevance of cholesterol as a key player of membrane-related processes.

Lipoproteins in Drosophila melanogaster—Assembly, Function, and Influence on Tissue Lipid Composition

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Palm, Wilhelm; Sampaio, Julio L.; Brankatschk, Marko; Carvalho, Maria; Mahmoud, Ali; Shevchenko, Andrej; Eaton, Suzanne

2012-01-01

Interorgan lipid transport occurs via lipoproteins, and altered lipoprotein levels correlate with metabolic disease. However, precisely how lipoproteins affect tissue lipid composition has not been comprehensively analyzed. Here, we identify the major lipoproteins of Drosophila melanogaster and use genetics and mass spectrometry to study their assembly, interorgan trafficking, and influence on tissue lipids. The apoB-family lipoprotein Lipophorin (Lpp) is the major hemolymph lipid carrier. It is produced as a phospholipid-rich particle by the fat body, and its secretion requires Microsomal Triglyceride Transfer Protein (MTP). Lpp acquires sterols and most diacylglycerol (DAG) at the gut via Lipid Transfer Particle (LTP), another fat body-derived apoB-family lipoprotein. The gut, like the fat body, is a lipogenic organ, incorporating both de novo–synthesized and dietary fatty acids into DAG for export. We identify distinct requirements for LTP and Lpp-dependent lipid mobilization in contributing to the neutral and polar lipid composition of the brain and wing imaginal disc. These studies define major routes of interorgan lipid transport in Drosophila and uncover surprising tissue-specific differences in lipoprotein lipid utilization. PMID:22844248

A Retrospective Cohort Study of the Potency of lipid-lowering therapy and Race-gender Differences in LDL cholesterol control

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Weiner Mark

2011-09-01

Full Text Available Abstract Background Reasons for race and gender differences in controlling elevated low density lipoprotein (LDL cholesterol may be related to variations in prescribed lipid-lowering therapy. We examined the effect of lipid-lowering drug treatment and potency on time until LDL control for black and white women and men with a baseline elevated LDL. Methods We studied 3,484 older hypertensive patients with dyslipidemia in 6 primary care practices over a 4-year timeframe. Potency of lipid-lowering drugs calculated for each treated day and summed to assess total potency for at least 6 and up to 24 months. Cox models of time to LDL control within two years and logistic regression models of control within 6 months by race-gender adjust for: demographics, clinical, health care delivery, primary/specialty care, LDL measurement, and drug potency. Results Time to LDL control decreased as lipid-lowering drug potency increased (P Conclusions Black women and, to a lesser extent, black men and white women were less likely to achieve LDL control than white men after accounting for lipid-lowering drug potency as well as diverse patient and provider factors. Future work should focus on the contributions of medication adherence and response to treatment to these clinically important differences.

Tissue sterol composition in Atlantic salmon (Salmo salar L.) depends on the dietary cholesterol content and on the dietary phytosterol:cholesterol ratio, but not on the dietary phytosterol content.

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Sissener, Nini H; Rosenlund, Grethe; Stubhaug, Ingunn; Liland, Nina S

2018-03-01

The aim of the study was to investigate how the dietary sterol composition, including cholesterol, phytosterol:cholesterol ratio and phytosterols, affect the absorption, biliary excretion, retention, tissue storage and distribution of cholesterol and individual phytosterols in Atlantic salmon (Salmo salar L.). A feeding trial was conducted at two different temperatures (6 and 12°C), using nine different diets with varying contents of phytosterols, cholesterol and phytosterol:cholesterol ratio. Cholesterol retention values were clearly dependent on dietary cholesterol, and showed that fish fed cholesterol levels phytosterol:cholesterol ratio, but not on the dietary phytosterol content in itself. Campesterol and brassicasterol appeared to be the phytosterols with the highest intestinal absorption in Atlantic salmon. There was a high biliary excretion of campesterol, but not of brassicasterol, which accumulated in tissues and particularly in adipose tissue, with 2-fold-higher retention at 12°C compared with 6°C. Campesterol had the second highest retention of the phytosterols in the fish, but with no difference between the two temperatures. Other phytosterols had very low retention. Although brassicasterol retention decreased with increasing dietary phytosterols, campesterol retention decreased with increasing dietary cholesterol, indicating differences in the uptake mechanisms for these two sterols.

JTT-130, a microsomal triglyceride transfer protein (MTP inhibitor lowers plasma triglycerides and LDL cholesterol concentrations without increasing hepatic triglycerides in guinea pigs

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Shrestha Sudeep

2005-09-01

Full Text Available Abstract Background Microsomal transfer protein inhibitors (MTPi have the potential to be used as a drug to lower plasma lipids, mainly plasma triglycerides (TG. However, studies with animal models have indicated that MTPi treatment results in the accumulation of hepatic TG. The purpose of this study was to evaluate whether JTT-130, a unique MTPi, targeted to the intestine, would effectively reduce plasma lipids without inducing a fatty liver. Methods Male guinea pigs (n = 10 per group were used for this experiment. Initially all guinea pigs were fed a hypercholesterolemic diet containing 0.08 g/100 g dietary cholesterol for 3 wk. After this period, animals were randomly assigned to diets containing 0 (control, 0.0005 or 0.0015 g/100 g of MTPi for 4 wk. A diet containing 0.05 g/100 g of atorvastatin, an HMG-CoA reductase inhibitor was used as the positive control. At the end of the 7th week, guinea pigs were sacrificed to assess drug effects on plasma and hepatic lipids, composition of LDL and VLDL, hepatic cholesterol and lipoprotein metabolism. Results Plasma LDL cholesterol and TG were 25 and 30% lower in guinea pigs treated with MTPi compared to controls (P Conclusion These results suggest that JTT-130 could have potential clinical applications due to its plasma lipid lowering effects with no alterations in hepatic lipid concentrations.

Cholesterol efflux is differentially regulated in neurons and astrocytes: implications for brain cholesterol homeostasis

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Chen, Jing; Zhang, Xiaolu; Kusumo, Handojo; Costa, Lucio G.; Guizzetti, Marina

2012-01-01

Disruption of cholesterol homeostasis in the central nervous system (CNS) has been associated with neurological, neurodegenerative, and neurodevelopmental disorders. The CNS is a closed system with regard to cholesterol homeostasis, as cholesterol-delivering lipoproteins from the periphery cannot pass the blood-brain-barrier and enter the brain. Different cell types in the brain have different functions in the regulation of cholesterol homeostasis, with astrocytes producing and releasing apolipoprotein E and lipoproteins, and neurons metabolizing cholesterol to 24(S)-hydroxycholesterol. We present evidence that astrocytes and neurons adopt different mechanisms also in regulating cholesterol efflux. We found that in astrocytes cholesterol efflux is induced by both lipid-free apolipoproteins and lipoproteins, while cholesterol removal from neurons is triggered only by lipoproteins. The main pathway by which apolipoproteins induce cholesterol efflux is through ABCA1. By upregulating ABCA1 levels and by inhibiting its activity and silencing its expression, we show that ABCA1 is involved in cholesterol efflux from astrocytes but not from neurons. Furthermore, our results suggest that ABCG1 is involved in cholesterol efflux to apolipoproteins and lipoproteins from astrocytes but not from neurons, while ABCG4, whose expression is much higher in neurons than astrocytes, is involved in cholesterol efflux from neurons but not astrocytes. These results indicate that different mechanisms regulate cholesterol efflux from neurons and astrocytes, reflecting the different roles that these cell types play in brain cholesterol homeostasis. These results are important in understanding cellular targets of therapeutic drugs under development for the treatments of conditions associated with altered cholesterol homeostasis in the CNS. PMID:23010475

Beneficial effects of aloe vera leaf gel extract on lipid profile status in rats with streptozotocin diabetes.

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Rajasekaran, Subbiah; Ravi, Kasiappan; Sivagnanam, Karuran; Subramanian, Sorimuthu

2006-03-01

The effect of diabetes mellitus on lipid metabolism is well established. The association of hyperglycaemia with an alteration of lipid parameters presents a major risk for cardiovascular complications in diabetes. Many secondary plant metabolites have been reported to possess lipid-lowering properties. The present study was designed to examine the potential anti-hyperlipidaemic efficacy of the ethanolic extract from Aloe vera leaf gel in streptozotocin (STZ)-induced diabetic rats. 2. Oral administration of Aloe vera gel extract at a dose of 300 mg/kg bodyweight per day to STZ-induced diabetic rats for a period of 21 days resulted in a significant reduction in fasting blood glucose, hepatic transaminases (aspartate aminotransferase and alanine aminotransferase), plasma and tissue (liver and kidney) cholesterol, triglycerides, free fatty acids and phospholipids and a significant improvement in plasma insulin. 3. In addition, the decreased plasma levels of high-density lipoprotein-cholesterol and increased plasma levels of low-density lipoprotein-and very low-density lipoprotein-cholesterol in diabetic rats were restored to near normal levels following treatment with the extract. 4. The fatty acid composition of the liver and kidney was analysed by gas chromatography. The altered fatty acid composition in the liver and kidney of diabetic rats was restored following treatment with the extract. 5. Thus, the results of the present study provide a scientific rationale for the use of Aloe vera as an antidiabetic agent.

Changes in lipid composition during sexual development of the malaria parasite Plasmodium falciparum.

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Tran, Phuong N; Brown, Simon H J; Rug, Melanie; Ridgway, Melanie C; Mitchell, Todd W; Maier, Alexander G

2016-02-06

The development of differentiated sexual stages (gametocytes) within human red blood cells is essential for the propagation of the malaria parasite, since only mature gametocytes will survive in the mosquito's midgut. Hence gametocytogenesis is a pre-requisite for transmission of the disease. Physiological changes involved in sexual differentiation are still enigmatic. In particular the lipid metabolism-despite being central to cellular regulation and development-is not well explored. Here the lipid profiles of red blood cells infected with the five different sexual stages of Plasmodium falciparum were analysed by mass spectrometry and compared to those from uninfected and asexual trophozoite infected erythrocytes. Fundamental differences between erythrocytes infected with the different parasite stages were revealed. In mature gametocytes many lipids that decrease in the trophozoite and early gametocyte infected red blood cells are regained. In particular, regulators of membrane fluidity, cholesterol and sphingomyelin, increased significantly during gametocyte maturation. Neutral lipids (serving mainly as caloriometric reserves) increased from 3 % of total lipids in uninfected to 27 % in stage V gametocyte infected red blood cells. The major membrane lipid class (phospholipids) decreased during gametocyte development. The lipid profiles of infected erythrocytes are characteristic for the particular parasite life cycle and maturity stages of gametocytes. The obtained lipid profiles are crucial in revealing the lipid metabolism of malaria parasites and identifying targets to interfere with this deadly disease.

Influence of polymer size, liposomal composition, surface charge, and temperature on the permeability of pH-sensitive liposomes containing lipid-anchored poly(2-ethylacrylic acid

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Lu T

2012-09-01

Full Text Available Tingli Lu,1 Zhao Wang,2 Yufan Ma,1 Yang Zhang,2 Tao Chen1,21Key Laboratory for Space Bioscience and Biotechnology, School of Life Science, Northwestern Polytechnical University, 2Liposome Research Centre, Xi'an, ChinaBackground: Liposomes containing pH-sensitive polymers are promising candidates for the treatment of tumors and localized infection. This study aimed to identify parameters influencing the extent of contents release from poly(ethylacrylic acid (PEAA vesicles, focusing on the effects of polymer size, lipid composition, vesicle surface charge, and temperature.Methods: Anchored lipid pH-sensitive PEAA was synthesized using PEAA with a molecular weight of 8.4 kDa. PEAA vesicles were prepared by insertion of the lipid-anchored PEAA into preformed large unilamellar vesicles. The preformed liposomes were manipulated by varying the phosphocholine and cholesterol content, and by adding negative or positive charges to the liposomes. A calcein release assay was used to evaluate the effects of polymer size, liposome composition, surface charge, and temperature on liposomal permeability.Results: The release efficiency of the calcein-entrapped vesicles was found to be dependent on the PEAA polymer size. PEAA vesicles containing a phosphatidylcholine to cholesterol ratio of 60:40 (mol/mol released more than 80% of their calcein content when the molecular weight of PEAA was larger than 8.4 kDa. Therefore, the same-sized polymer of 8.4 kDa was used for the rest of study. The calcein release potential was found to decrease as the percentage of cholesterol increased and with an increase in the phosphocholine acyl chain length (DMPC . DPPC . DSPC. Negatively charged and neutral vesicles released similar amounts of calcein, whereas positively charged liposomes released a significant amount of their contents. pH-sensitive release was dependent on temperature. Dramatic content release was observed at higher temperatures.Conclusion: The observed

Tritium labelling of a cholesterol amphiphile designed for cell membrane anchoring of proteins.

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Schäfer, Balázs; Orbán, Erika; Kele, Zoltán; Tömböly, Csaba

2015-01-01

Cell membrane association of proteins can be achieved by the addition of lipid moieties to the polypeptide chain, and such lipid-modified proteins have important biological functions. A class of cell surface proteins contains a complex glycosylphosphatidylinositol (GPI) glycolipid at the C-terminus, and they are accumulated in cholesterol-rich membrane microdomains, that is, lipid rafts. Semisynthetic lipoproteins prepared from recombinant proteins and designed lipids are valuable probes and model systems of the membrane-associated proteins. Because GPI-anchored proteins can be reinserted into the cell membrane with the retention of the biological function, they are appropriate candidates for preparing models via reduction of the structural complexity. A synthetic headgroup was added to the 3β-hydroxyl group of cholesterol, an essential lipid component of rafts, and the resulting cholesterol derivative was used as a simplified GPI mimetic. In order to quantitate the membrane integrated GPI mimetic after the exogenous addition to live cells, a tritium labelled cholesterol anchor was prepared. The radioactive label was introduced into the headgroup, and the radiolabelled GPI mimetic anchor was obtained with a specific activity of 1.37 TBq/mmol. The headgroup labelled cholesterol derivative was applied to demonstrate the sensitive detection of the cell membrane association of the anchor under in vivo conditions. Copyright © 2015 John Wiley & Sons, Ltd.

Kefir consumption does not alter plasma lipid levels or cholesterol fractional synthesis rates relative to milk in hyperlipidemic men: a randomized controlled trial [ISRCTN10820810

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Mafu Akier

2002-01-01

Full Text Available Abstract Background Fermented milk products have been shown to affect serum cholesterol concentrations in humans. Kefir, a fermented milk product, has been traditionally consumed for its potential health benefits but has to date not been studied for its hypocholesterolemic properties. Methods Thirteen healthy mildly hypercholesterolemic male subjects consumed a dairy supplement in randomized crossover trial for 2 periods of 4 wk each. Subjects were blinded to the dairy supplement consumed. Blood samples were collected at baseline and after 4 wk of supplementation for measurement of plasma total, low-density lipoprotein, and high-density lipoprotein cholesterol and triglyceride concentrations, as well as fatty acid profile and cholesterol synthesis rate. Fecal samples were collected at baseline and after 2 and 4 wk of supplementation for determination of fecal short chain fatty acid level and bacterial content. Results Kefir had no effect on total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglyceride concentrations nor on cholesterol fractional synthesis rates after 4 wk of supplementation. No significant change on plasma fatty acid levels was observed with diet. However, both kefir and milk increased (p Conclusions Since kefir consumption did not result in lowered plasma lipid concentrations, the results of this study do not support consumption of kefir as a cholesterol-lowering agent.

Cholesterol Hydroperoxide Generation, Translocation, and Reductive Turnover in Biological Systems.

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Girotti, Albert W; Korytowski, Witold

2017-12-01

Cholesterol is like other unsaturated lipids in being susceptible to peroxidative degradation upon exposure to strong oxidants like hydroxyl radical or peroxynitrite generated under conditions of oxidative stress. In the eukaryotic cell plasma membrane, where most of the cellular cholesterol resides, peroxidation leads to membrane structural and functional damage from which pathological states may arise. In low density lipoprotein, cholesterol and phospholipid peroxidation have long been associated with atherogenesis. Among the many intermediates/products of cholesterol oxidation, hydroperoxide species (ChOOHs) have a number of different fates and deserve special attention. These fates include (a) damage-enhancement via iron-catalyzed one-electron reduction, (b) damage containment via two-electron reduction, and (c) inter-membrane, inter-lipoprotein, and membrane-lipoprotein translocation, which allows dissemination of one-electron damage or off-site suppression thereof depending on antioxidant location and capacity. In addition, ChOOHs can serve as reliable and conveniently detected mechanistic reporters of free radical-mediated reactions vs. non-radical (e.g., singlet oxygen)-mediated reactions. Iron-stimulated peroxidation of cholesterol and other lipids underlies a newly discovered form of regulated cell death called ferroptosis. These and other deleterious consequences of radical-mediated lipid peroxidation will be discussed in this review.

Lipid control and use of lipid-regulating drugs for prevention of cardiovascular events in Chinese type 2 diabetic patients: a prospective cohort study

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Tong Peter CY

2010-11-01

Full Text Available Abstract Background Dyslipidaemia is an important but modifiable risk factor of cardiovascular disease (CVD in type 2 diabetes. Yet, the effectiveness of lipid regulating drugs in Asians is lacking. We examined the effects of lipid control and treatment with lipid regulating drugs on new onset of CVD in Chinese type 2 diabetic patients. Methods In this prospective cohort consisting of 4521 type 2 diabetic patients without history of CVD and naïve for lipid regulating treatment recruited consecutively from 1996 to 2005, 371 developed CVD after a median follow-up of 4.9 years. We used Cox proportional hazard regression to obtain the hazard ratios (HR of lipids and use of lipid regulating drugs for risk of CVD. Results The multivariate-adjusted HR (95% confidence interval of CVD in patients with high LDL-cholesterol (≥ 3.0 mmol/L was 1.36 (1.08 - 1.71, compared with lower values. Using the whole range value of HDL-cholesterol, the risk of CVD was reduced by 41% with every 1 mmol/L increase in HDL-cholesterol. Plasma triglyceride did not predict CVD. Statins use was associated with lower CVD risk [HR = 0.66 (0.50 - 0.88]. In sub-cohort analysis, statins use was associated with a HR of 0.60 (0.44 - 0.82 in patients with high LDL-cholesterol (≥ 3.0 mmol/L and 0.49 (0.28 - 0.88 in patients with low HDL-cholesterol. In patients with LDL-cholesterol Conclusions In Chinese type 2 diabetic patients, high LDL-cholesterol and low HDL-cholesterol predicted incident CVD. Overall, patients treated with statins had 40-50% risk reduction in CVD compared to non-users.

Superovulation Induced Changes of Lipid Metabolism in Ovaries and Embryos and Its Probable Mechanism.

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Li-Ya Wang

Full Text Available This research was intended to investigate the fetal origins of changed birth weight of the offspring born through assisted reproductive technology (ART. The association between hormone and lipid metabolism or body weight has been generally accepted, and as the basic and specific treatment in ART procedure, gonadotropin stimulation might have potential effects on intrauterine lipid metabolism. In our studies, the mice were superovulated with two doses of gonadotropin. The cholesterol metabolism in ovaries and the triglyceride metabolism in embryos were analyzed. The results showed gonadotropin probably accelerated luteinization and induced a longer time follicle development and ovulation, which resulted in histological and morphological alteration of ovary, and increased the cholesterol content and the expressions of steroidogenesis-related genes. In embryos, gonadotropin increased lipid accumulation and decreased fatty acid synthesis in a dose-dependent manner. Moreover, the changes of fatty acid composition were also shown in superovulation groups. Our studies firstly provided the evidence that the superovulation might affect the maternal and fetal lipid metabolism. These variations of lipid metabolism in our results may be associated with birth weight of ART infants.

Optimization of Liposomal Lipid Composition for a New, Reactive Sulfur Donor, and In Vivo Efficacy Studies on Mice to Antagonize Cyanide Intoxication

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Ilona Petrikovics

2011-01-01

Full Text Available Present studies have focused on a novel cyanide antidotal system, on the coencapsulation of a new sulfur donor DTO with rhodanese within sterically stabilized liposomes. The optimal lipid composition for coencapsulation of DTO with rhodanese is the combination of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, cholesterol, cationic lipid (DOTAP, and 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol-2000] ammonium salt (with molar ratios of 82.7 : 9.2 : 3.0 : 5.1. With the optimized compositions, prophylactic and therapeutic in vivo efficacy studies were carried out in a mice model. When DTO was coencapsulated with rhodanese and thiosulfate the prophylactic antidotal protection was 4.9×LD50. Maximum antidotal protection against cyanide intoxication (15×LD50 was achieved with coencapsulated rhodanese and DTO/thiosulfate in combination with sodium nitrite. When applied therapeutically, 100% survival rate (6/6 was achieved at 20 mg/kg cyanide doses with the encapsulated DTO-rhodanese-thiosulfate antidotal systems with and without sodium nitrite. These data are indicating that the appropriately formulated DTO is a promising sulfur donor for cyanide antagonism.

Lipid exchange between Borrelia burgdorferi and host cells.

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Jameson T Crowley

2013-01-01

Full Text Available Borrelia burgdorferi, the agent of Lyme disease, has cholesterol and cholesterol-glycolipids that are essential for bacterial fitness, are antigenic, and could be important in mediating interactions with cells of the eukaryotic host. We show that the spirochetes can acquire cholesterol from plasma membranes of epithelial cells. In addition, through fluorescent and confocal microscopy combined with biochemical approaches, we demonstrated that B. burgdorferi labeled with the fluorescent cholesterol analog BODIPY-cholesterol or (3H-labeled cholesterol transfer both cholesterol and cholesterol-glycolipids to HeLa cells. The transfer occurs through two different mechanisms, by direct contact between the bacteria and eukaryotic cell and/or through release of outer membrane vesicles. Thus, two-way lipid exchange between spirochetes and host cells can occur. This lipid exchange could be an important process that contributes to the pathogenesis of Lyme disease.

[Lipid profile from low socioeconomic level preschool children. Valencia, Venezuela].

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Solano, Liseti; Velásquez, Emma; Naddaf, Gloria; Páez, María

2003-01-01

Overweight and obesity are a public health problem worldwide affecting adults and children as well. The aim of this study was to assess overweight, lipid profile and cardiovascular risk ratios in 390 preschool children from low socio-economic level from Valencia, Venezuela. Nutritional anthropometric evaluation measured by body dimensions, and serum determination of cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol and cardiovascular risk factors, were determined. 95% of the children were in relative and critical poverty. 14.3% of undernutrition and 20.8% of overweight was found. Lipid profile was in normal range, with no significant differences by sex, but higher values for HDL-cholesterol and risk ratios were found in children aged 1 to 3.99 years. Even though no differences were found by nutritional status, overweight children had higher values for lipids, except HDL-cholesterol. 6.3% of overweight children had cholesterol > or =170 mg/dL, 16.5% LDL-cholesterol > or =110 mg/dL, 40.5% triglycerides > or =75mg/dL and 100% HDL-cholesterol <45 mg/dL. Overweight and lipid profile alterations were present in an important group of the children, which increase their risk of obesity and chronic non-transmissible diseases. Nutritional and educational intervention should be addressed.

Cholesterol monohydrate nucleation in ultrathin films on water

DEFF Research Database (Denmark)

Rapaport, H.; Kuzmenko, I.; Lafont, S.

2001-01-01

The growth of a cholesterol crystalline phase, three molecular layers thick at the air-water interface, was monitored by grazing incidence x-ray diffraction and x-ray reflectivity. Upon compression, a cholesterol film transforms from a monolayer of trigonal symmetry and low crystallinity to a tri......The growth of a cholesterol crystalline phase, three molecular layers thick at the air-water interface, was monitored by grazing incidence x-ray diffraction and x-ray reflectivity. Upon compression, a cholesterol film transforms from a monolayer of trigonal symmetry and low crystallinity...... in pathological lipid deposits....

Consumption of a dietary portfolio of cholesterol lowering foods improves blood lipids without affecting concentrations of fat soluble compounds.

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Ramprasath, Vanu R; Jenkins, David J A; Lamarche, Benoit; Kendall, Cyril W C; Faulkner, Dorothea; Cermakova, Luba; Couture, Patrick; Ireland, Chris; Abdulnour, Shahad; Patel, Darshna; Bashyam, Balachandran; Srichaikul, Korbua; de Souza, Russell J; Vidgen, Edward; Josse, Robert G; Leiter, Lawrence A; Connelly, Philip W; Frohlich, Jiri; Jones, Peter J H

2014-10-18

Consumption of a cholesterol lowering dietary portfolio including plant sterols (PS), viscous fibre, soy proteins and nuts for 6 months improves blood lipid profile. Plant sterols reduce blood cholesterol by inhibiting intestinal cholesterol absorption and concerns have been raised whether PS consumption reduces fat soluble vitamin absorption. The objective was to determine effects of consumption of a cholesterol lowering dietary portfolio on circulating concentrations of PS and fat soluble vitamins. Using a parallel design study, 351 hyperlipidemic participants from 4 centres across Canada were randomized to 1 of 3 groups. Participants followed dietary advice with control or portfolio diet. Participants on routine and intensive portfolio involved 2 and 7 clinic visits, respectively, over 6 months. No changes in plasma concentrations of α and γ tocopherol, lutein, lycopene and retinol, but decreased β-carotene concentrations were observed with intensive (week 12: p = 0.045; week 24: p = 0.039) and routine (week 12: p = 0.031; week 24: p = 0.078) portfolio groups compared to control. However, cholesterol adjusted β-carotene and fat soluble compound concentrations were not different compared to control. Plasma PS concentrations were increased with intensive (campesterol:p = 0.012; β-sitosterol:p = 0.035) and routine (campesterol: p = 0.034; β-sitosterol: p = 0.080) portfolio groups compared to control. Plasma cholesterol-adjusted campesterol and β-sitosterol concentrations were negatively correlated (p portfolio diet reduces serum total and LDL-C levels while increasing PS values, without altering fat soluble compounds concentrations. The extent of increments of PS with the current study are not deleterious and also maintaining optimum levels of fat soluble vitamins are of paramount necessity to maintain overall metabolism and health. Results indicate portfolio diet as one of the best options for CVD risk reduction

Effects of Dimethyl Sulfoxide in Cholesterol-Containing Lipid Membranes: A Comparative Study of Experiments In Silico and with Cells

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de Ménorval, Marie-Amélie; Mir, Lluis M.; Fernández, M. Laura; Reigada, Ramon

2012-01-01

Dimethyl sulfoxide (DMSO) has been known to enhance cell membrane permeability of drugs or DNA. Molecular dynamics (MD) simulations with single-component lipid bilayers predicted the existence of three regimes of action of DMSO: membrane loosening, pore formation and bilayer collapse. We show here that these modes of action are also reproduced in the presence of cholesterol in the bilayer, and we provide a description at the atomic detail of the DMSO-mediated process of pore formation in cholesterol-containing lipid membranes. We also successfully explore the applicability of DMSO to promote plasma membrane permeability to water, calcium ions (Ca2+) and Yo-Pro-1 iodide (Yo-Pro-1) in living cell membranes. The experimental results on cells in culture can be easily explained according to the three expected regimes: in the presence of low doses of DMSO, the membrane of the cells exhibits undulations but no permeability increase can be detected, while at intermediate DMSO concentrations cells are permeabilized to water and calcium but not to larger molecules as Yo-Pro-1. These two behaviors can be associated to the MD-predicted consequences of the effects of the DMSO at low and intermediate DMSO concentrations. At larger DMSO concentrations, permeabilization is larger, as even Yo-Pro-1 can enter the cells as predicted by the DMSO-induced membrane-destructuring effects described in the MD simulations. PMID:22848583

Effect of beef tallow on growth performance, carcass characteristics, meat composition, and lipid profile of growing lambs

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Shahana Ahmed

2015-09-01

Full Text Available The objective of this study was to investigate the effect of diets with inclusion of beef tallow on growth, and carcass characteristics, meat quality, and lipid profile in growing lambs. The experiment was conducted with 15 lambs for 63 days. The lambs were randomly allotted into three dietary treatments (T0, T1, and T2 with five animals in each group; T0 (control diet without beef tallow, T1 (diet with 2% beef tallow, and T2 (diet with 4% beef tallow. The body weight and feed conversion ratio (FCR were significantly (P0.05 on meat quality and chemical composition among the three dietary groups. Group T1 showed the highest increase of cholesterol concentration (11.5% at the end of experiment, but serum triglyceride concentration was not significantly (P>0.05 correlated with any of the three dietary groups. To sum up, the use of beef tallow at 2% level in lamb diet can increase their performance without having any deleterious effect on carcass, meat quality and lipid profile. [J Adv Vet Anim Res 2015; 2(3.000: 346-352

Associations of Body Composition Measurements with Serum Lipid, Glucose and Insulin Profile: A Chinese Twin Study

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Liao, Chunxiao; Gao, Wenjing; Cao, Weihua; Lv, Jun; Yu, Canqing; Wang, Shengfeng; Zhou, Bin; Pang, Zengchang; Cong, Liming; Wang, Hua; Wu, Xianping; Li, Liming

2015-01-01

Objectives To quantitate and compare the associations of various body composition measurements with serum metabolites and to what degree genetic or environmental factors affect obesity-metabolite relation. Methods Body mass index (BMI), waist circumference (WC), lean body mass (LBM), percent body fat (PBF), fasting serum high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides (TG), total cholesterol (TC), glucose, insulin and lifestyle factors were assessed in 903 twins from Chinese National Twin Registry (CNTR). Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated from fasting serum glucose and insulin. Linear regression models and bivariate structural equation models were used to examine the relation of various body composition measurements with serum metabolite levels and genetic/environmental influences on these associations, respectively. Results At individual level, adiposity measurements (BMI, WC and PBF) showed significant associations with serum metabolite concentrations in both sexes and the associations still existed in male twins when using within-MZ twin pair comparison analyses. Associations of BMI with TG, insulin and HOMA-IR were significantly stronger in male twins compared to female twins (BMI-by-sex interaction p = 0.043, 0.020 and 0.019, respectively). Comparison of various adiposity measurements with levels of serum metabolites revealed that WC explained the largest fraction of variance in serum LDL-C, TG, TC and glucose concentrations while BMI performed best in explaining variance in serum HDL-C, insulin and HOMA-IR levels. Of these phenotypic correlations, 64–81% were attributed to genetic factors, whereas 19–36% were attributed to unique environmental factors. Conclusions We observed different associations between adiposity and serum metabolite profile and demonstrated that WC and BMI explained the largest fraction of variance in serum lipid profile and insulin

Early Effect of High Dose of Ionizing Radiation Exposure on Plasma Lipids Profile and Liver Fatty Acids Composition in Rats

International Nuclear Information System (INIS)

Noaman, E.; Mansour, S.Z.; Ibrahim, N.K.

2005-01-01

The present study was conducted to analyze the effect of acute gamma-irradiation on rats at supralethal doses of 20 Gy to determine the synthesis and amounts of free fatty acids, neutral lipids and phospholipids of plasma and liver after 24 and 48 h of gamma-irradiation. Male Wistar rats weighing 120+- 20 g were exposed to 20 Gy of gamma radiation (dose rate of 0.59 Gy/min). Exposure of rats to ionizing radiation resulted in significant alterations in the assayed parameters indicating lipid metabolism disturbance. Plasma cholesterol and phospholipid levels increased up to 71.3 and 71.5 %, respectively, after 24 h from radiation exposure and then returned to 28 and 27 % change in-compare with control values after 48 h post-irradiation. Plasma triacylglycerol concentrations increased concomitantly with irradiation, but their values are less high than cholesterol and phospholipid levels recording significant changes at 19 and 9 % comparing with control rats. Lipid peroxidation measured as MDA recorded significant elevation after 24 and 48 h post irradiation. It was shown that the synthesis of free fatty acids, cholesterol, cholesterol ethers and phospholipids was activated 48 h after irradiation at 20 Gy. The amount of free fatty acids of the rat liver decreased at 20 Gy exposures. This is assumed to be a result of the radioresistance to some degree in the system of free fatty acid synthesis of the rat to the gamma-irradiation in the lethal doses

Bile salt-induced cholesterol crystal formation from model bile vesicles: a time course study

NARCIS (Netherlands)

van de Heijning, B. J.; Stolk, M. F.; van Erpecum, K. J.; Renooij, W.; Groen, A. K.; vanBerge-Henegouwen, G. P.

1994-01-01

Precipitation of cholesterol crystals from vesicles is an important step in the pathogenesis of cholesterol gallstones. Little is known, however, about the kinetics and the mechanisms involved in cholesterol crystallization. Therefore, the time course of cholesterol crystal precipitation and lipid

Horse meat consumption affects iron status, lipid profile and fatty acid composition of red blood cells in healthy volunteers.

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Del Bó, Cristian; Simonetti, Paolo; Gardana, Claudio; Riso, Patrizia; Lucchini, Giorgio; Ciappellano, Salvatore

2013-03-01

This study investigated the effect of moderate consumption of horse meat on iron status, lipid profile and fatty acid composition of red blood cells in healthy male volunteers. Fifty-two subjects were randomly assigned to two groups of 26 subjects each: a test group consuming two portions of 175 g/week of horse meat, and a control group that abstained from eating horse meat during the 90 days trial. Before and after 90 days, blood samples were collected for analysis. Horse meat consumption significantly (p ≤ 0.05) reduced serum levels of total and low-density lipoprotein cholesterol ( - 6.2% and - 9.1%, respectively) and transferrin ( - 4.6%). Total n - 3, long chain polyunsaturated fatty acids n - 3 and docosahexeanoic acid content in erythrocytes increased (p ≤ 0.05) by about 7.8%, 8% and 11%, respectively. In conclusion, the regular consumption of horse meat may contribute to the dietary intake of n - 3 polyunsaturated fatty acids and may improve lipid profile and iron status in healthy subjects.

Human immunodeficiency virus impairs reverse cholesterol transport from macrophages.

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Zahedi Mujawar

2006-10-01

Full Text Available Several steps of HIV-1 replication critically depend on cholesterol. HIV infection is associated with profound changes in lipid and lipoprotein metabolism and an increased risk of coronary artery disease. Whereas numerous studies have investigated the role of anti-HIV drugs in lipodystrophy and dyslipidemia, the effects of HIV infection on cellular cholesterol metabolism remain uncharacterized. Here, we demonstrate that HIV-1 impairs ATP-binding cassette transporter A1 (ABCA1-dependent cholesterol efflux from human macrophages, a condition previously shown to be highly atherogenic. In HIV-1-infected cells, this effect was mediated by Nef. Transfection of murine macrophages with Nef impaired cholesterol efflux from these cells. At least two mechanisms were found to be responsible for this phenomenon: first, HIV infection and transfection with Nef induced post-transcriptional down-regulation of ABCA1; and second, Nef caused redistribution of ABCA1 to the plasma membrane and inhibited internalization of apolipoprotein A-I. Binding of Nef to ABCA1 was required for down-regulation and redistribution of ABCA1. HIV-infected and Nef-transfected macrophages accumulated substantial amounts of lipids, thus resembling foam cells. The contribution of HIV-infected macrophages to the pathogenesis of atherosclerosis was supported by the presence of HIV-positive foam cells in atherosclerotic plaques of HIV-infected patients. Stimulation of cholesterol efflux from macrophages significantly reduced infectivity of the virions produced by these cells, and this effect correlated with a decreased amount of virion-associated cholesterol, suggesting that impairment of cholesterol efflux is essential to ensure proper cholesterol content in nascent HIV particles. These results reveal a previously unrecognized dysregulation of intracellular lipid metabolism in HIV-infected macrophages and identify Nef and ABCA1 as the key players responsible for this effect. Our findings

Electron paramagnetic resonance (EPR spectral components of spin-labeled lipids in saturated phospholipid bilayers: effect of cholesterol

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Heverton Silva Camargos

2013-01-01

Full Text Available Electron paramagnetic resonance (EPR spectroscopy was used to study the main structural accommodations of spin labels in bilayers of saturated phosphatidylcholines with acyl chain lengths ranging from 16 to 22 carbon atoms. EPR spectra allowed the identification of two distinct spectral components in thermodynamic equilibrium at temperatures below and above the main phase transition. An accurate analysis of EPR spectra, using two fitting programs, enabled determination of the thermodynamic profile for these major probe accommodations. Focusing the analysis on two-component EPR spectra of a spin-labeled lipid, the influence of 40 mol % cholesterol in DPPC was studied.

Mechanistic evaluation of the transfection barriers involved in lipid-mediated gene delivery: Interplay between nanostructure and composition

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Pozzi, D.; Marchini, C.; Cardarelli, F.; Salomone, F.; Coppola, S.; Montani, M.; Zabaleta, M. Elexpuru; Digman, M.A.; Gratton, E.; Colapicchioni, V.; Caracciolo, G.

2014-01-01

Here we present a quantitative mechanism-based investigation aimed at comparing the cell uptake, intracellular trafficking, endosomal escape and final fate of lipoplexes and lipid–protamine/deoxyribonucleic acid (DNA) (LPD) nanoparticles (NPs) in living Chinese hamster ovary (CHO) cells. As a model, two lipid formulations were used for comparison. The first formulation is made of the cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and the zwitterionic lipid dioleoylphosphocholine (DOPC), while the second mixture is made of the cationic 3β-[N-(N,N-dimethylaminoethane)-carbamoyl] cholesterol (DC-Chol) and the zwitterionic helper lipid dioleoylphosphatidylethanolamine (DOPE). Our findings indicate that lipoplexes are efficiently taken up through fluid-phase macropinocytosis, while a less efficient uptake of LPD NPs occurs through a combination of both macropinocytosis and clathrin-dependent pathways. Inside the cell, both lipoplexes and LPD NPs are actively transported towards the cell nucleus, as quantitatively addressed by spatio-temporal image correlation spectroscopy (STICS). For each lipid formulation, LPD NPs escape from endosomes more efficiently than lipoplexes. When cells were treated with DOTAP–DOPC-containing systems the majority of the DNA was trapped in the lysosome compartment, suggesting that extensive lysosomal degradation was the rate-limiting factors in DOTAP–DOPC-mediated transfection. On the other side, escape from endosomes is large for DC-Chol–DOPE-containing systems most likely due to DOPE and cholesterol-like molecules, which are able to destabilize the endosomal membrane. The lipid-dependent and structure-dependent enhancement of transfection activity suggests that DNA is delivered to the nucleus synergistically: the process requires both the membrane-fusogenic activity of the nanocarrier envelope and the employment of lipid species with intrinsic endosomal rupture ability. PMID:24296066

Evaluation the Effect Garlet Tablet on Serum Lipid Profile

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F. Emami

2006-07-01

Full Text Available Introduction & Objective: Some investigators reported significant effect of garlic on serum cholesterol reduction. In addition, Iranian culture has specific belief on herbs and garlic in this regard. Our goal in this study was to evaluate the effect of garlet tablets on serum lipid profile.Materials & Methods: Sixty patients were randomly divided into two groups for evaluation of the effect of garlic on their lipid profile. The first group was low fat regimen group and the second was garlet tablet regimen group. Total cholesterol, LDL cholesterol, HDL cholesterol and triglyceride levels were measured in both groups. Then, after two months of these regimens administration, these items were measured again and were compared.Results: Mean age, sex and baseline initial lipid levels were similar in both groups. Total cholesterol and LDL cholesterol levels were decreased significantly in the garlic regimen group (in spite of non significant reduction in the other group. Triglyceride and HDL levels were not changed significantly in both regimen groups. Conclusion: Garlet tablet administration has more significant reductive effect on cholestrol level than low cholesterol diet.

The effect of ghee (clarified butter) on serum lipid levels and microsomal lipid peroxidation.

Science.gov (United States)

Sharma, Hari; Zhang, Xiaoying; Dwivedi, Chandradhar

2010-04-01

Ghee, also known as clarified butter, has been utilized for thousands of years in Ayurveda as a therapeutic agent. In ancient India, ghee was the preferred cooking oil. In the last several decades, ghee has been implicated in the increased prevalence of coronary artery disease (CAD) in Asian Indians due to its content of saturated fatty acids and cholesterol and, in heated ghee, cholesterol oxidation products. Our previous research on Sprague-Dawley outbred rats, which serve as a model for the general population, showed no effect of 5 and 10% ghee-supplemented diets on serum cholesterol and triglycerides. However, in Fischer inbred rats, which serve as a model for genetic predisposition to diseases, results of our previous research showed an increase in serum total cholesterol and triglyceride levels when fed a 10% ghee-supplemented diet. In the present study, we investigated the effect of 10% dietary ghee on microsomal lipid peroxidation, as well as serum lipid levels in Fischer inbred rats to assess the effect of ghee on free radical mediated processes that are implicated in many chronic diseases including cardiovascular disease. Results showed that 10% dietary ghee fed for 4 weeks did not have any significant effect on levels of serum total cholesterol, but did increase triglyceride levels in Fischer inbred rats. Ghee at a level of 10% in the diet did not increase liver microsomal lipid peroxidation or liver microsomal lipid peroxide levels. Animal studies have demonstrated many beneficial effects of ghee, including dose-dependent decreases in serum total cholesterol, low density lipoprotein (LDL), very low density lipoprotein (VLDL), and triglycerides; decreased liver total cholesterol, triglycerides, and cholesterol esters; and a lower level of nonenzymatic-induced lipid peroxidation in liver homogenate. Similar results were seen with heated (oxidized) ghee which contains cholesterol oxidation products. A preliminary clinical study showed that high doses of

Cholesterol affects the interaction between an ionic liquid and phospholipid vesicles. A study by differential scanning calorimetry and nanoplasmonic sensing.

Science.gov (United States)

Russo, Giacomo; Witos, Joanna; Rantamäki, Antti H; Wiedmer, Susanne K

2017-12-01

The present work aims at studying the interactions between cholesterol-rich phosphatidylcholine-based lipid vesicles and trioctylmethylphosphonium acetate ([P 8881 ][OAc]), a biomass dissolving ionic liquid (IL). The effect of cholesterol was assayed by using differential scanning calorimetry (DSC) and nanoplasmonic sensing (NPS) measurement techniques. Cholesterol-enriched dipalmitoyl-phosphatidylcholine vesicles were exposed to different concentrations of the IL, and the derived membrane perturbation was monitored by DSC. The calorimetric data could suggest that the binding and infiltration of the IL are delayed in the vesicles containing cholesterol. To clarify our findings, NPS was applied to quantitatively follow the resistance of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine incorporating 0, 10, and 50mol% of cholesterol toward the IL exposure over time. The membrane perturbation induced by different concentrations of IL was found to be a concentration dependent process on cholesterol-free lipid vesicles. Moreover, our results showed that lipid depletion in cholesterol-enriched lipid vesicles is inversely proportional to the increasing amount of cholesterol in the vesicles. These findings support that cholesterol-rich lipid bilayers are less susceptible toward membrane disrupting agents as compared to membranes that do not incorporate any sterols. This probably occurs because cholesterol tightens the phospholipid acyl chain packing of the plasma membranes, increasing their resistance and reducing their permeability. Copyright © 2017 Elsevier B.V. All rights reserved.

Intensity of lipid oxidation and formation of cholesterol oxidation products during frozen storage of raw and cooked chicken

OpenAIRE

Conchillo, A. (Ana); Ansorena, D. (Diana); Astiasarán, I. (Iciar)

2004-01-01

Raw and cooked chicken breasts were stored at −18 °C for 3 months under aerobic and vacuum conditions, and the intensity of lipid oxidation and the formation of COP (cholesterol oxidation products) were studied. Raw samples showed low COP levels (4.60–7.40 µg g−1 fat), TBARS (thiobarbituric acid reactive substances) levels (0.01–0.03 mg kg−1) and peroxide values (not detected) under both aerobic and vacuum conditions. Cooked samples (grilled and roasted) showed TBARS levels of 0.36–0.99 mg kg...

Fatty acid composition of the pollen lipids of Cycas revoluta Thunb

International Nuclear Information System (INIS)

Sidorov, R.A.; Kuznetsova, E.I.; Pchelkin, V.P.; Zhukov, A.V.; Gorshkova, E.N.; Tsydendambaev, V.D.

2016-01-01

The fatty acid (FA) composition of total extractable and non extractable with chloroform lipids of C. revoluta pollen was determined. Among other minor FAs, unusual Δ5 polymethylene-interrupted FA, Δ5, 11-octadecadienoic acid was found. This FA was found in the seed lipids of C. revoluta earlier, but it was discovered for the first time in pollen lipids. [es

Ex Vivo Antioxidant Activity of Selected Medicinal Plants against Fenton Reaction-Mediated Oxidation of Biological Lipid Substrates

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Namratha Pai Kotebagilu

2015-01-01

Full Text Available Free radical-mediated oxidation is often linked to various degenerative diseases. Biological substrates with lipids as major components are susceptible to oxygen-derived lipid peroxidation due to their composition. Lipid peroxide products act as biomarkers in evaluating the antioxidant potential of various plants and functional foods. The study focused on evaluation of the antioxidant potential of two extracts (methanol and 80% methanol of four medicinal plants, Andrographis paniculata, Costus speciosus, Canthium parviflorum, and Abrus precatorius, against Fenton reaction-mediated oxidation of three biological lipid substrates; cholesterol, low-density lipoprotein, and brain homogenate. The antioxidant activity of the extracts was measured by thiobarbituric acid reactive substances method. Also, the correlation between the polyphenol, flavonoid content, and the antioxidant activity in biological substrates was analyzed. Results indicated highest antioxidant potential by 80% methanol extract of Canthium parviflorum (97.55%, methanol extract of Andrographis paniculata (72.15%, and methanol extract of Canthium parviflorum (49.55% in cholesterol, low-density lipoprotein, and brain, respectively. The polyphenol and flavonoid contents of methanol extract of Andrographis paniculata in cholesterol (r=0.816 and low-density lipoprotein (r=0.948 and Costus speciosus in brain (r=0.977, polyphenols, and r=0.949, flavonoids correlated well with the antioxidant activity. The findings prove the antioxidant potential of the selected medicinal plants against Fenton reaction in biological lipid substrates.

Dietary exposure to shiitake mushroom confers reductions in serum glucose, lipids, leptin and antioxidant capacity in rats

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Previously, we showed that dietary intake of shiitake mushroom (Lentinus edodes) decreased serum levels of polar lipids in rats. This study evaluated the effects of lifelong consumption of shiitake on body composition and serum cholesterol-related- and anti-oxidant indices in rats. Rat dams and th...

Effect of physical exercise on blood lipids and adipose tissue composition in young healthy men

NARCIS (Netherlands)

Danner, S. A.; Wieling, W.; Havekes, L.; Leuven, J. G.; Smit, E. M.; Dunning, A. J.

1984-01-01

In a prospective, controlled study, the influence of strenuous physical exercise on plasma total cholesterol, HDL cholesterol, apolipoprotein A-I, total triglycerides and fatty acid composition of adipose tissue was studied during 7 months of training in 15 senior oarsmen and 21 controls matched for

Structure of cholesterol/ceramide monolayer mixtures

DEFF Research Database (Denmark)

Scheffer, L.; Solomonov, I.; Weygand, M.J.

2005-01-01

The structure of monolayers of cholesterol/ ceramide mixtures was investigated using grazing incidence x-ray diffraction, immunofluorescence, and atomic force microscopy techniques. Grazing incidence x-ray diffraction measurements showed the existence of a crystalline mixed phase of the two....... As ceramide incorporates the lipid backbone common to all sphingolipids, this arrangement may be relevant to the understanding of the molecular organization of lipid rafts....

THE ROLE OF GROWTH HORMONE IN LIPID METABOLISM

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I Gusti Ayu Dewi Ratnayanti

2013-04-01

Full Text Available Growth hormone (GH is one of the hormones that regulate metabolism, including lipid metabolism. GH can regulate the amount of fat in the tissue and also the level of lipid profile. Growth hormone affects the lipid in the tissue and blood by modulating the lipid metabolism, especially through the regulation of synthesis, excretion and breakdown of internal lipids. Research showed that GH could consistently lower the level of total cholesterol and LDL, whereas its effect on triglyceride and HDL level showed varying results. Growth hormone induces lypolisis by stimulating the activity of HSL and LPL and thereby influenced the triglyceride level and tissue fat storage. Cholesterol and lipoprotein levels are controlled by regulating the synthesis of cholesterol by lowering the activity of HMGCoA reductase. The excretion of cholesterol through the bile is also enhanced by stimulating the activity of enzymes C7?OH. The breakdown of VLDL and LDL are enhanced by increasing the expression of LDL receptor and ApoE as well as affecting the editing of mRNA ApoB100. Increase activity of LPL is also known to be the important factor in the HDL metabolism

The role of tetraether lipid composition in the adaptation of thermophilic archaea to acidity.

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Boyd, Eric S; Hamilton, Trinity L; Wang, Jinxiang; He, Liu; Zhang, Chuanlun L

2013-01-01

Diether and tetraether lipids are fundamental components of the archaeal cell membrane. Archaea adjust the degree of tetraether lipid cyclization in order to maintain functional membranes and cellular homeostasis when confronted with pH and/or thermal stress. Thus, the ability to adjust tetraether lipid composition likely represents a critical phenotypic trait that enabled archaeal diversification into environments characterized by extremes in pH and/or temperature. Here we assess the relationship between geochemical variation, core- and polar-isoprenoid glycerol dibiphytanyl glycerol tetraether (C-iGDGT and P-iGDGT, respectively) lipid composition, and archaeal 16S rRNA gene diversity and abundance in 27 geothermal springs in Yellowstone National Park, Wyoming. The composition and abundance of C-iGDGT and P-iGDGT lipids recovered from geothermal ecosystems were distinct from surrounding soils, indicating that they are synthesized endogenously. With the exception of GDGT-0 (no cyclopentyl rings), the abundances of individual C-iGDGT and P-iGDGT lipids were significantly correlated. The abundance of a number of individual tetraether lipids varied positively with the relative abundance of individual 16S rRNA gene sequences, most notably crenarchaeol in both the core and polar GDGT fraction and sequences closely affiliated with Candidatus Nitrosocaldus yellowstonii. This finding supports the proposal that crenarchaeol is a biomarker for nitrifying archaea. Variation in the degree of cyclization of C- and P-iGDGT lipids recovered from geothermal mats and sediments could best be explained by variation in spring pH, with lipids from acidic environments tending to have, on average, more internal cyclic rings than those from higher pH ecosystems. Likewise, variation in the phylogenetic composition of archaeal 16S rRNA genes could best be explained by spring pH. In turn, the phylogenetic similarity of archaeal 16S rRNA genes was significantly correlated with the similarity

The Role of Tetraether Lipid Composition in the Adaptation of Thermophilic Archaea to Acidity

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Boyd, Eric S.; Hamilton, Trinity L.; Wang, Jinxiang; He, Liu; Zhang, Chuanlun L.

2013-01-01

Diether and tetraether lipids are fundamental components of the archaeal cell membrane. Archaea adjust the degree of tetraether lipid cyclization in order to maintain functional membranes and cellular homeostasis when confronted with pH and/or thermal stress. Thus, the ability to adjust tetraether lipid composition likely represents a critical phenotypic trait that enabled archaeal diversification into environments characterized by extremes in pH and/or temperature. Here we assess the relationship between geochemical variation, core- and polar-isoprenoid glycerol dibiphytanyl glycerol tetraether (C-iGDGT and P-iGDGT, respectively) lipid composition, and archaeal 16S rRNA gene diversity and abundance in 27 geothermal springs in Yellowstone National Park, Wyoming. The composition and abundance of C-iGDGT and P-iGDGT lipids recovered from geothermal ecosystems were distinct from surrounding soils, indicating that they are synthesized endogenously. With the exception of GDGT-0 (no cyclopentyl rings), the abundances of individual C-iGDGT and P-iGDGT lipids were significantly correlated. The abundance of a number of individual tetraether lipids varied positively with the relative abundance of individual 16S rRNA gene sequences, most notably crenarchaeol in both the core and polar GDGT fraction and sequences closely affiliated with Candidatus Nitrosocaldus yellowstonii. This finding supports the proposal that crenarchaeol is a biomarker for nitrifying archaea. Variation in the degree of cyclization of C- and P-iGDGT lipids recovered from geothermal mats and sediments could best be explained by variation in spring pH, with lipids from acidic environments tending to have, on average, more internal cyclic rings than those from higher pH ecosystems. Likewise, variation in the phylogenetic composition of archaeal 16S rRNA genes could best be explained by spring pH. In turn, the phylogenetic similarity of archaeal 16S rRNA genes was significantly correlated with the similarity

Protective potentials of wild rice (Zizania latifolia (Griseb) Turcz) against obesity and lipotoxicity induced by a high-fat/cholesterol diet in rats.

Science.gov (United States)

Han, Shu-Fen; Zhang, Hong; Zhai, Cheng-Kai

2012-07-01

The study evaluates the protective potentials of wild rice against obesity and lipotoxicity induced by a high-fat/cholesterol diet in rats. In addition to the rats of low-fat diet group, others animals were exposed to a high-fat/cholesterol diet condition for 8 weeks. The city diet (CD) is based on the diet consumed by urban residents in modern China, which is rich in fat/cholesterol and high in carbohydrates from white rice and processed wheat starch. The chief source of dietary carbohydrates of wild rice diet (WRD) is from Chinese wild rice and other compositions are the same with CD. Rats fed CD showed elevated body and liver organ weights, lipid profiles, free fatty acids (FFA) and leptin comparable with rats fed high-fat/cholesterol diet (HFD) known to induce obesity and hyperlipidaemia in this species. However, rats consuming WRD suppressed the increase of lipid droplets accumulation, FFA, and leptin, and the decrease of lipoprotein lipase and adipose triglyceride lipase. Meanwhile, WRD prevented high-fat/cholesterol diet-induced elevation in protein expression of sterol-regulatory element binding protein-1c, and gene expression of fatty acid synthase and acetyl-CoA carboxylase. These findings indicate that wild rice as a natural food has the potentials of preventing obesity and liver lipotoxicity induced by a high-fat/cholesterol diet in rats. Copyright © 2012 Elsevier Ltd. All rights reserved.

Impact of age, gender and diabetes on serum lipid levels

International Nuclear Information System (INIS)

Adnan, M.; Shabbir, I.; Ali, Z.; Ali, S.F.; Rahat, T.

2013-01-01

Objectives:To see the effects of age, gender and diabetes on serum lipid levels. Study type, settings and duration:Cross sectional analytical study conducted at PMRC Research Centre, Fatima Jinnah Medical College,Lahore from Jun-Dec 2011. Materials and Methods: One hundred type 2 diabetes mellitus and equal numbers of gender matched healthy controls were randomly selected for the study. After an overnight fasting, blood specimens were drawn for lipid profile where total cholesterol,high density lipoprotein cholesterol and triglycerides were measured by standard enzymatic endpoint methods and LDL-cholesterol by Friedweld's formula. Statistical analysis was done using SPSS-15. Results Odd ratios of age for total cholesterol (OR 1.198); high density lipoprotein cholesterol (OR 1.144); and low density lipoprotein cholesterol (OR 1.576) revealed that subjects aged 45 years or more had greater risk of having deranged lipid levels. Female gender had higher high density lipoprotein cholesterol (p 0.000); and triglycerides (p 0.001). Odd ratios of men for total cholesterol (OR 0.775); high density lipoprotein cholesterol(OR 0.183); and low density lipoprotein Cholesterol (OR 0.683) illustrated that men were significantly less prone to dyslipidemia than women. Odd ratio of diabetes for high density lipoprotein cholesterol (OR 1.802) suggested that diabetics had 1.8 times more risk of having low high density lipoprotein cholesterol. Conclusions: Diabetic females over 45 years of age have significantly high chances of having disturbed or high lipid profile. Policy message:All persons in general and diabetics in particular over the age of 45 years should be screened for dyslipidemia and informed using behavior change communication to prevent disease complications. (author)

Impact of age, gender and diabetes on serum lipid levels

Energy Technology Data Exchange (ETDEWEB)

Adnan, M.; Shabbir, I.; Ali, Z.; Ali, S. F.; Rahat, T. [Fatima Jinnah Medical College, Lahore (Pakistan)

2013-01-15

Objectives:To see the effects of age, gender and diabetes on serum lipid levels. Study type, settings and duration:Cross sectional analytical study conducted at PMRC Research Centre, Fatima Jinnah Medical College,Lahore from Jun-Dec 2011. Materials and Methods: One hundred type 2 diabetes mellitus and equal numbers of gender matched healthy controls were randomly selected for the study. After an overnight fasting, blood specimens were drawn for lipid profile where total cholesterol,high density lipoprotein cholesterol and triglycerides were measured by standard enzymatic endpoint methods and LDL-cholesterol by Friedweld's formula. Statistical analysis was done using SPSS-15. Results Odd ratios of age for total cholesterol (OR 1.198); high density lipoprotein cholesterol (OR 1.144); and low density lipoprotein cholesterol (OR 1.576) revealed that subjects aged 45 years or more had greater risk of having deranged lipid levels. Female gender had higher high density lipoprotein cholesterol (p 0.000); and triglycerides (p 0.001). Odd ratios of men for total cholesterol (OR 0.775); high density lipoprotein cholesterol(OR 0.183); and low density lipoprotein Cholesterol (OR 0.683) illustrated that men were significantly less prone to dyslipidemia than women. Odd ratio of diabetes for high density lipoprotein cholesterol (OR 1.802) suggested that diabetics had 1.8 times more risk of having low high density lipoprotein cholesterol. Conclusions: Diabetic females over 45 years of age have significantly high chances of having disturbed or high lipid profile. Policy message:All persons in general and diabetics in particular over the age of 45 years should be screened for dyslipidemia and informed using behavior change communication to prevent disease complications. (author)

Cholesterol Contributes to Diabetic Nephropathy through SCAP-SREBP-2 Pathway

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Hong Sun

2013-01-01

Full Text Available Diabetic nephropathy (DN has been associated with the presence of lipid deposition. We hypothesized that the disruption of intracellular cholesterol feedback may contribute to DN. Diabetes was induced by high fat/sucrose diet and low-dose intraperitoneal injection of streptozocin (STZ in male Sprague-Dawley rats. Then diabetic rats were randomly divided into two groups: untreated diabetic group (DM and atorvastatin-treated group (DM + AT. We found that the levels of serum blood urea nitrogen and creatinine, as well as 24-hour urine protein and urinary neutrophil gelatinase-associated lipocalin, were significantly increased in diabetic rats. This result indicated that the diabetic rats suffered from functional renal damage. We also observed lipid droplet accumulation and increase in 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoAR, low density lipoprotein receptor (LDLr, sterol regulatory element binding protein-2 (SREBP-2, and SREBP-cleavage activating protein (SCAP in the kidneys of diabetic rats. However, atorvastatin ameliorated renal lipid accumulation and improved the renal function of diabetic rats despite an increase in mRNA and protein expressions of HMG-CoAR, LDLr, and SREBP-2. These results demonstrated that intracellular cholesterol feedback regulation is disrupted in rats with type 2 diabetes, thereby causing renal cholesterol accumulation. Atorvastatin ameliorated renal cholesterol accumulation by reducing renal cholesterol synthesis.

Cholesterol inhibits entotic cell-in-cell formation and actomyosin contraction.

Science.gov (United States)

Ruan, Banzhan; Zhang, Bo; Chen, Ang; Yuan, Long; Liang, Jianqing; Wang, Manna; Zhang, Zhengrong; Fan, Jie; Yu, Xiaochen; Zhang, Xin; Niu, Zubiao; Zheng, You; Gu, Songzhi; Liu, Xiaoqing; Du, Hongli; Wang, Jufang; Hu, Xianwen; Gao, Lihua; Chen, Zhaolie; Huang, Hongyan; Wang, Xiaoning; Sun, Qiang

2018-01-01

Cell-in-cell structure is prevalent in human cancer, and associated with several specific pathophysiological phenomena. Although cell membrane adhesion molecules were found critical for cell-in-cell formation, the roles of other membrane components, such as lipids, remain to be explored. In this study, we attempted to investigate the effects of cholesterol and phospholipids on the formation of cell-in-cell structures by utilizing liposome as a vector. We found that Lipofectamine-2000, the reagent commonly used for routine transfection, could significantly reduce entotic cell-in-cell formation in a cell-specific manner, which is correlated with suppressed actomyosin contraction as indicated by reduced β-actin expression and myosin light chain phosphorylation. The influence on cell-in-cell formation was likely dictated by specific liposome components as some liposomes affected cell-in-cell formation while some others didn't. Screening on a limited number of lipids, the major components of liposome, identified phosphatidylethanolamine (PE), stearamide (SA), lysophosphatidic acid (LPA) and cholesterol (CHOL) as the inhibitors of cell-in-cell formation. Importantly, cholesterol treatment significantly inhibited myosin light chain phosphorylation, which resembles the effect of Lipofectamine-2000, suggesting cholesterol might be partially responsible for liposomes' effects on cell-in-cell formation. Together, our findings supporting a role of membrane lipids and cholesterol in cell-in-cell formation probably via regulating actomyosin contraction. Copyright © 2017 Elsevier Inc. All rights reserved.

Cholesterol, sphingolipids, and glycolipids: What do we know about their role in raft-like membranes?

DEFF Research Database (Denmark)

Rog, T.; Vattulainen, I.

2014-01-01

Lipids rafts are considered to be functional nanoscale membrane domains enriched in cholesterol and sphingolipids, characteristic in particular of the external leaflet of cell membranes. Lipids, together with membrane-associated proteins, are therefore considered to form nanoscale units with pote......Lipids rafts are considered to be functional nanoscale membrane domains enriched in cholesterol and sphingolipids, characteristic in particular of the external leaflet of cell membranes. Lipids, together with membrane-associated proteins, are therefore considered to form nanoscale units...... with potential specific functions. Although the understanding of the structure of rafts in living cells is quite limited, the possible functions of rafts are widely discussed in the literature, highlighting their importance in cellular functions. In this review, we discuss the understanding of rafts that has...... emerged based on recent atomistic and coarse-grained molecular dynamics simulation studies on the key lipid raft components, which include cholesterol, sphingolipids, glycolipids, and the proteins interacting with these classes of lipids. The simulation results are compared to experiments when possible...

High ratio of triglycerides to hdl-cholesterol predicts extensive coronary disease

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Protasio Lemos da Luz

2008-01-01

Full Text Available An abnormal ratio of triglycerides to HDL-cholesterol (TG/HDL-c indicates an atherogenic lipid profile and a risk for the development of coronary disease. OBJECTIVE: To investigate the association between lipid levels, specifically TG/HDL-c, and the extent of coronary disease. METHODS: High-risk patients (n = 374 submitted for coronary angiography had their lipid variables measured and coronary disease extent scored by the Friesinger index. RESULTS: The subjects consisted of 220 males and 154 females, age 57.2 ± 11.1 years, with total cholesterol of 210± 50.3 mg/dL, triglycerides of 173.8 ± 169.8 mg/dL, HDL-cholesterol (HDL-c of 40.1 ± 12.8 mg/dL, LDL-cholesterol (LDL-c of 137.3 ± 46.2 mg/dL, TG/HDL-c of 5.1 ± 5.3, and a Friesinger index of 6.6 ± 4.7. The relationship between the extent of coronary disease (dichotomized by a Friesenger index of 5 and lipid levels (normal vs. abnormal was statistically significant for the following: triglycerides, odds ratio of 2.02 (1.31-3.1; p = 0.0018; HDL-c, odds ratio of 2.21 (1.42-3.43; p = 0.0005; and TG/HDL-c, odds ratio of 2.01(1.30-3.09; p = 0.0018. However, the relationship was not significant between extent of coronary disease and total cholesterol [1.25 (0.82-1.91; p = 0.33] or LDL-c [1.47 (0.96-2.25; p = 0.0842]. The chi-square for linear trends for Friesinger > 4 and lipid quartiles was statistically significant for triglycerides (p = 0.0017, HDL-c (p = 0.0001, and TG/HDL-c (p = 0.0018, but not for total cholesterol (p = 0.393 or LDL-c (p = 0.0568. The multivariate analysis by logistic regression OR gave 1.3 ± 0.79 (p = .0001 for TG/HDL-c, 0.779 ± 0.074 (p = .0001 for HDL-c, and 1.234 ± 0.097 (p = 0.03 for LDL. Analysis of receiver operating characteristic curves showed that only TG/HDL-c and HDL-c were useful for detecting extensive coronary disease, with the former more strongly associated with disease. CONCLUSIONS: Although some lipid variables were associated with the extent of

Sex-Specific Associations Between Thyrotropin and Serum Lipid Profiles

DEFF Research Database (Denmark)

Meisinger, Christa; Ittermann, Till; Tiller, Daniel

2014-01-01

BACKGROUND: Population-based studies investigating the sex-specific association between thyrotropin (TSH) levels and serum lipid concentrations are scarce. We examined the association between TSH and total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL......) cholesterol, and triglycerides in men and women from the general population. Furthermore, the association with TSH outside and within the reference range and lipid levels was studied. METHODS: Individual data of 13,571 men and women without lipid medication of four population-based studies conducted...... in Western European adults were pooled for cross-sectional analyses. The association between TSH levels and lipid concentrations were analyzed by calculating sex-specific multivariable median regression models. RESULTS: In the pooled population, serum TSH levels were significantly positively associated...

Probing the binding of cationic lipids with dendrimers.

Science.gov (United States)

Mandeville, J S; Bourassa, P; Tajmir-Riahi, H A

2013-01-14

Polycationic polymers are used extensively in biology to disrupt cell membranes and thus enhance the transport of materials into the cell. We report the bindings of several lipids cholesterol (Chol), 1,2-dioleoyl-3-trimethylammonium-propane(DOTAP), dioctadecyldimethylammoniumbromide (DDAB), and dioleoylphosphatidylethanolamine (DOPE) to dendrimers of different compositions such as mPEG-PAMAM (G3), mPEG-PAMAM (G4), and PAMAM (G4) under physiological conditions. FTIR, UV-visible spectroscopic, methods and molecular modeling were used to analyze the lipid binding mode, the binding constant, and the effects of lipid complexation on the dendrimer structure. The structural analysis showed that lipids bind dendrimers through both hydrophilic and hydrophobic contacts with overall binding constants of K(chol-mPEG-G3) = 1.7 × 10(3) M(-1), K(chol-mPEG-PAMAM-G4) = 2.7 × 10(3) M(-1), K(chol-PAMAM-G4) = 1.0 × 10(3) M(-1), K(DOPE-mPEG-G3) = 1.5 × 10(3) M(-1), K(DOPE-mPEG-PAMAM-G4) = 1.6 × 10(3) M(-1), K(DOPE-PAMAM-G4) = 5.3 × 10(2) M(-1), K(DDAB-mPEG-G3) = 1.5 × 10(3) M(-1), K(DDAB-mPEG-PAMAM-G4) = 1.9 × 10(2) M(-1), K(DDAB-PAMAM-G4) = 7.0 × 10(2) M(-1), K(DOTAP-mPEG-G3) = 1.9 × 10(3) M(-1), K(DOTAP-mPEG-PAMAM-G4) = 1.5 × 10(3) M(-1), and K(DOTAP-PAMAM-G4) = 5.7 × 10(2) M(-1). Weaker interaction was observed as dendrimer cationic charges increased. The free binding energies from docking were -5.15 (cholesterol), -5.79 (DDAB), and -5.36 kcal/mol (DOTAP) with the order of stability DDAB-PAMAM-G-4 > DOTAP-PAMAM-G4 > cholesterol-PAMAM-G4, consistent with the spectroscopic results. Dendrimers might act as carriers to transport lipids in vitro.

Phytosterol ester processing in the small intestine: impact on cholesterol availability for absorption and chylomicron cholesterol incorporation in healthy humans[S

Science.gov (United States)

Amiot, Marie Josèphe; Knol, Diny; Cardinault, Nicolas; Nowicki, Marion; Bott, Romain; Antona, Claudine; Borel, Patrick; Bernard, Jean-Paul; Duchateau, Guus; Lairon, Denis

2011-01-01

Phytosterols (plant sterols and stanols) can lower intestinal cholesterol absorption, but the complex dynamics of the lipid digestion process in the presence of phytosterol esters (PEs) are not fully understood. We performed a clinical experiment in intubated healthy subjects to study the time course of changes in the distribution of all lipid moieties present in duodenal phases during 4 h of digestion of meals with 3.2 g PE (PE meal) or without (control meal) PE. In vitro experiments under simulated gastrointestinal conditions were also performed. The addition of PE did not alter triglyceride (TG) hydrolysis in the duodenum or subsequent chylomicron TG occurrence in the circulation. In contrast, cholesterol accumulation in the duodenum aqueous phase was markedly reduced in the presence of PE (−32%, P < 0.10). In vitro experiments confirmed that PE reduces cholesterol transfer into the aqueous phase. The addition of PE resulted in a markedly reduced presence of meal-derived hepta-deuterated cholesterol in the circulation, i.e., in chylomicrons (−43%, PE meal vs. control; P < 0.0001) and plasma (−54%, PE meal vs. control; P < 0.0001). The present data show that addition of PE to a meal does not alter TG hydrolysis but displaces cholesterol from the intestinal aqueous phase and lowers chylomicron cholesterol occurrence in humans. PMID:21482714

Cholesterol and fatty acids oxidation in meat from three muscles of Massese suckling lambs slaughtered at different weights

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Andrea Serra

2014-09-01

Full Text Available Eighteen Massese male lambs fed mainly with maternal milk were slaughtered at 11, 14 and 17 kg. Samples of Longissimus dorsi (LD, Triceps brachii (TB and Semimembranosus (Sm muscles were collected. Total intramuscular lipids were extracted by means of a mixture of chloroform methanol 2/1. Cholesterol content and its oxidation product (COP were determined by a gas chromatography apparatus equipped with an apolar 30 m column. Fatty acid oxidation was evaluated by means of thiobarbituric acid reactive substances (TBARS extracting the sample with aqueous acidic solution. The effect of slaughter weight on oxidation of intramuscular lipids was found only in TB muscles. In this muscle the cholesterol content showed a decreasing trend, while the content of COPs significantly increased with the age of animals. Among the COPs, the 7-ketocholesterol and 7β-hydroxycholesterol were the most abundant, followed by α- and β- epoxy-cholesterol and cholestan-triol. The content of TBARS did not vary owing to a similar fatty acid composition of intramuscular fat across weight of slaughter. In any case, the values of TBARS did not reach the threshold of the detection of off-flavour in meat.

A Moderate Zinc Deficiency Does Not Alter Lipid and Fatty Acid Composition in the Liver of Weanling Rats Fed Diets Rich in Cocoa Butter or Safflower Oil.

Science.gov (United States)

Weigand, Edgar; Egenolf, Jennifer

2017-01-01

The aim of the study was to examine whether a moderate zinc deficiency alters hepatic lipid composition. Male weanling rats, assigned to five groups (8 animals each), were fed low-carbohydrate high-fat diets supplemented with 7 or 50 mg Zn/kg (LZ or HZ) and 22% cocoa butter (CB) or 22% safflower oil (SF) for four weeks. One group each had free access to the LZ-CB and LZ-SF diets, one group each was restrictedly fed the HZ-CB and HZ-SF diets in matching amounts, and one group had free access to the HZ-SF diet (ad libitum control). The rats fed the LZ diets had significantly lower energy intakes and final body weights than the ad libitum control group, and lower plasma and femur Zn concentrations than the animals consuming the HZ diets. Hepatic cholesterol, triacylglycerol and phospholipid concentrations, and fatty acid composition of hepatic triacylglycerols and phospholipids did not significantly differ between the LZ and their respective HZ groups, but were greatly affected by dietary fat source. In conclusion, the moderate Zn deficiency did not significantly alter liver lipid concentrations and fatty acid composition.

A Moderate Zinc Deficiency Does Not Alter Lipid and Fatty Acid Composition in the Liver of Weanling Rats Fed Diets Rich in Cocoa Butter or Safflower Oil

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Edgar Weigand

2017-01-01

Full Text Available The aim of the study was to examine whether a moderate zinc deficiency alters hepatic lipid composition. Male weanling rats, assigned to five groups (8 animals each, were fed low-carbohydrate high-fat diets supplemented with 7 or 50 mg Zn/kg (LZ or HZ and 22% cocoa butter (CB or 22% safflower oil (SF for four weeks. One group each had free access to the LZ-CB and LZ-SF diets, one group each was restrictedly fed the HZ-CB and HZ-SF diets in matching amounts, and one group had free access to the HZ-SF diet (ad libitum control. The rats fed the LZ diets had significantly lower energy intakes and final body weights than the ad libitum control group, and lower plasma and femur Zn concentrations than the animals consuming the HZ diets. Hepatic cholesterol, triacylglycerol and phospholipid concentrations, and fatty acid composition of hepatic triacylglycerols and phospholipids did not significantly differ between the LZ and their respective HZ groups, but were greatly affected by dietary fat source. In conclusion, the moderate Zn deficiency did not significantly alter liver lipid concentrations and fatty acid composition.

Increased hepatic cholesterol esterification with essential fatty acid deficiency (EFAD): relationship to plasma lipoprotein (LP) cholesterol content

International Nuclear Information System (INIS)

Ney, D.M.; Ziboh, V.A.; Schneeman, B.O.

1986-01-01

EFAD in the rat is associated with hepatic accumulation of esterified cholesterol and altered distribution of cholesterol between plasma and hepatic tissue. Little is known regarding the impact of EFAD on LP composition. To determine the relationship between hepatic cholesterol esterification and plasma lP composition in control (C) and EFAD male Wistar rats, the authors induced EFAD with continuous intragastric (IG) infusion of EFA-free solutions containing 3.5% of calories as triolein for 7 and 14 days. C animals received IG infusion of solutions containing 3.5% of calories as linoleic acid. Data in the EFAD groups reveal: (i) marked decreases in hepatic EFAs and increases in monoenoic acids; (ii) progressive increases in hepatic content of triglyceride and esterified cholesterol with 7 and 14 days of feeding; (iii) assay of acyl CoA:cholesterol acyltransferase activity in hepatic tissue using 14 C-cholesterol demonstrates an increase in hepatic cholesterol esterification when compared to C animals. Increased hepatic cholesterol esterification correlates with elevated levels of esterified cholesterol in plasma VLDL and HDL particles. These data indicate that the elevated levels of cholesterol esters in LP particles is due, at least in part, to increased hepatic cholesterol esterification with EFAD

MILD CHOLESTEROL DEPLETION REDUCES AMYLOID-β PRODUCTION BY IMPAIRING APP TRAFFICKING TO THE CELL SURFACE

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Guardia-Laguarta, Cristina; Coma, Mireia; Pera, Marta; Clarimón, Jordi; Sereno, Lidia; Agulló, José M.; Molina-Porcel, Laura; Gallardo, Eduard; Deng, Amy; Berezovska, Oksana; Hyman, Bradley T.; Blesa, Rafael; Gómez-Isla, Teresa; Lleó, Alberto

2009-01-01

It has been suggested that cellular cholesterol levels can modulate the metabolism of the amyloid precursor protein (APP) but the underlying mechanism remains controversial. In the current study, we investigate in detail the relationship between cholesterol reduction, APP processing and γ-secretase function in cell culture studies. We found that mild membrane cholesterol reduction led to a decrease in Aβ40 and Aβ42 in different cell types. We did not detect changes in APP intracellular domain or Notch intracellular domain generation. Western blot analyses showed a cholesterol-dependent decrease in the APP C-terminal fragments and cell surface APP. Finally, we applied a fluorescence resonance energy transfer (FRET)-based technique to study APP-Presenilin 1 (PS1) interactions and lipid rafts in intact cells. Our data indicate that cholesterol depletion reduces association of APP into lipid rafts and disrupts APP-PS1 interaction. Taken together, our results suggest that mild membrane cholesterol reduction impacts the cleavage of APP upstream of γ-secretase and appears to be mediated by changes in APP trafficking and partitioning into lipid rafts. PMID:19457132

Grape tannin catechin and ethanol fluidify oral membrane mimics containing moderate amounts of cholesterol: Implications on wine tasting?

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Furlan, Aurélien L; Saad, Ahmad; Dufourc, Erick J; Géan, Julie

2016-11-01

Wine tasting results in interactions of tannin-ethanol solutions with proteins and lipids of the oral cavity. Among the various feelings perceived during tasting, astringency and bitterness most probably result in binding events with saliva proteins, lipids and receptors. In this work, we monitored the conjugated effect of the grape polyphenol catechin and ethanol on lipid membranes mimicking the different degrees of keratinization of oral cavity surfaces by varying the amount of cholesterol present in membranes. Both catechin and ethanol fluidify the membranes as evidenced by solid-state 2 H NMR of perdeuterated lipids. The effect is however depending on the cholesterol proportion and may be very important and cumulative in the absence of cholesterol or presence of 18 mol % cholesterol. For 40 mol % cholesterol, mimicking highly keratinized membranes, both ethanol and catechin can no longer affect membrane dynamics. These observations can be accounted for by phase diagrams of lipid-cholesterol mixtures and the role played by membrane defects for insertion of tannins and ethanol when several phases coexist. These findings suggest that the behavior of oral membranes in contact with wine should be different depending of their cholesterol content. Astringency and bitterness could be then affected; the former because of a potential competition between the tannin-lipid and the tannin-saliva protein interaction, and the latter because of a possible fluidity modification of membranes containing taste receptors. The lipids that have been up to now weakly considered in oenology may be become a new actor in the issue of wine tasting. Copyright © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Effect of dietary supplementation with olive and sunflower oils on lipid profile and liver histology in rats fed high cholesterol diet.

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Duavy, Sandra Mara Pimentel; Salazar, Gerson Javier Torres; Leite, Gerlânia de Oliveira; Ecker, Assis; Barbosa, Nilda Vargas

2017-06-01

To compare the effects of high-monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA) against the metabolic disorders elicited by a high-cholesterol diet (HC) in rats. Using in vivo dietary manipulation, rats were fed with different diets containing 4% soybean oil (cholesterol free diet) and 1% HC containing 12% olive oil (HC + OO) enriched with MUFA and 12% sunflower oil (HC + SO) enriched with PUFA for 60 d. Serum lipid levels and hepatic steatosis were evaluated after the treatment period. Comparatively, rats treated with HC + OO diet experienced a decrease in the serum LDL-C, VLDL-C and CT levels compared to those fed with HC + SO diet (P blood. Copyright © 2017 Hainan Medical University. Production and hosting by Elsevier B.V. All rights reserved.

Lipid Microarray Biosensor for Biotoxin Detection.

Energy Technology Data Exchange (ETDEWEB)

Singh, Anup K.; Throckmorton, Daniel J.; Moran-Mirabal, Jose C.; Edel, Joshua B.; Meyer, Grant D.; Craighead, Harold G.

2006-05-01

We present the use of micron-sized lipid domains, patterned onto planar substrates and within microfluidic channels, to assay the binding of bacterial toxins via total internal reflection fluorescence microscopy (TIRFM). The lipid domains were patterned using a polymer lift-off technique and consisted of ganglioside-populated DSPC:cholesterol supported lipid bilayers (SLBs). Lipid patterns were formed on the substrates by vesicle fusion followed by polymer lift-off, which revealed micron-sized SLBs containing either ganglioside GT1b or GM1. The ganglioside-populated SLB arrays were then exposed to either Cholera toxin subunit B (CTB) or Tetanus toxin fragment C (TTC). Binding was assayed on planar substrates by TIRFM down to 1 nM concentration for CTB and 100 nM for TTC. Apparent binding constants extracted from three different models applied to the binding curves suggest that binding of a protein to a lipid-based receptor is strongly affected by the lipid composition of the SLB and by the substrate on which the bilayer is formed. Patterning of SLBs inside microfluidic channels also allowed the preparation of lipid domains with different compositions on a single device. Arrays within microfluidic channels were used to achieve segregation and selective binding from a binary mixture of the toxin fragments in one device. The binding and segregation within the microfluidic channels was assayed with epifluorescence as proof of concept. We propose that the method used for patterning the lipid microarrays on planar substrates and within microfluidic channels can be easily adapted to proteins or nucleic acids and can be used for biosensor applications and cell stimulation assays under different flow conditions. KEYWORDS. Microarray, ganglioside, polymer lift-off, cholera toxin, tetanus toxin, TIRFM, binding constant.4

Cholesterol, Triglycerides, and the Five-Factor Model of Personality

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Sutin, Angelina R.; Terracciano, Antonio; Deiana, Barbara; Uda, Manuela; Schlessinger, David; Lakatta, Edward G.; Costa, Paul T.

2010-01-01

Unhealthy lipid levels are among the leading controllable risk factors for coronary heart disease. To identify the psychological factors associated with dyslipidemia, this study investigates the personality correlates of cholesterol (total, LDL, and HDL) and triglycerides. A community-based sample (N=5,532) from Sardinia, Italy, had their cholesterol and triglyceride levels assessed and completed a comprehensive personality questionnaire, the NEO-PI-R. All analyses controlled for age, sex, BMI, smoking, drinking, hypertension, and diabetes. Low Conscientiousness and traits related to impulsivity were associated with lower HDL cholesterol and higher triglycerides. Compared to the lowest 10%, those who scored in top 10% on Impulsivity had a 2.5 times greater risk of exceeding the clinical threshold for elevated triglycerides (OR=2.51, CI=1.56–4.07). In addition, sex moderated the association between trait depression (a component of Neuroticism) and HDL cholesterol, such that trait depression was associated with lower levels of HDL cholesterol in women but not men. When considering the connection between personality and health, unhealthy lipid profiles may be one intermediate biomarker between personality and morbidity and mortality. PMID:20109519

Critical role of the lipid rafts in caprine herpesvirus type 1 infection in vitro.

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Pratelli, Annamaria; Colao, Valeriana

2016-01-04

The fusion machinery for herpesvirus entry in the host cells involves the interactions of viral glycoproteins with cellular receptors, although additional viral and cellular domains are required. Extensive areas of the plasma membrane surface consist of lipid rafts organized into cholesterol-rich microdomains involved in signal transduction, protein sorting, membrane transport and in many processes of viruses infection. Because of the extraction of cholesterol leads to disorganization of lipid microdomains and to dissociation of proteins bound to the lipid rafts, we investigated the effect of cholesterol depletion by methyl-β-cyclodextrin (MβCD) on caprine herpesvirus 1 (CpHV.1) in three important phases of virus infection such as binding, entry and post-entry. MβCD treatment did not prejudice virus binding to cells, while a dose-dependent reduction of the virus yield was observed at the virus entry stage, and 30 mM MβCD reduced infectivity evidently. Treatment of MDBK after virus entry revealed a moderate inhibitory effect suggesting that cholesterol is mainly required during virus entry rather than during the post-entry stage. Alteration of the envelope lipid composition affected virus entry and a noticeable reduction in virus infectivity was detected in the presence of 15 mM MβCD. Considering that the recognition of a host cell receptor is a crucial step in the start-up phase of infection, these data are essential for the study of CpHV.1 pathogenesis. To date virus receptors for CpHV.1 have not yet been identified and further investigations are required to state that MβCD treatment affects the expression of the viral receptors. Copyright © 2015 Elsevier B.V. All rights reserved.

Multimodal nonlinear imaging of atherosclerotic plaques differentiation of triglyceride and cholesterol deposits

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Christian Matthäus

2014-09-01

Full Text Available Cardiovascular diseases in general and atherothrombosis as the most common of its individual disease entities is the leading cause of death in the developed countries. Therefore, visualization and characterization of inner arterial plaque composition is of vital diagnostic interest, especially for the early recognition of vulnerable plaques. Established clinical techniques provide valuable morphological information but cannot deliver information about the chemical composition of individual plaques. Therefore, spectroscopic imaging techniques have recently drawn considerable attention. Based on the spectroscopic properties of the individual plaque components, as for instance different types of lipids, the composition of atherosclerotic plaques can be analyzed qualitatively as well as quantitatively. Here, we compare the feasibility of multimodal nonlinear imaging combining two-photon fluorescence (TPF, coherent anti-Stokes Raman scattering (CARS and second-harmonic generation (SHG microscopy to contrast composition and morphology of lipid deposits against the surrounding matrix of connective tissue with diffraction limited spatial resolution. In this contribution, the spatial distribution of major constituents of the arterial wall and atherosclerotic plaques like elastin, collagen, triglycerides and cholesterol can be simultaneously visualized by a combination of nonlinear imaging methods, providing a powerful label-free complement to standard histopathological methods with great potential for in vivo application.

Effect of age and gender on lipid profile in healthy rural population of ...

African Journals Online (AJOL)

There are contradicting information on the influence of age and gender on blood lipid profile, some researchers believe the levels of total cholesterol and other components of lipid profile increase with age, others have proved significant negative correlation between total cholesterol, low density lipoprotein cholesterol and ...

Secular trends in lipid-lowering treatment and lipid levels after a first acute myocardial infarction

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Lena Björck

2008-01-01

Full Text Available Lena Björck1, Catharina Welin2, Annika Rosengren11Department of medicine, Sahlgrenska University Hospital/Östra, Göteborg, Sweden; 2Institute of Health and Care Sciences, the Sahlgrenska Academy at Göteborg University, Göteborg, SwedenBackground: The beneficial effects of statins were unequivocally demonstrated in the Scandinavian Simvastatin Survival Study (4S in 1994, leading to an increase in the use of lipid-lowering drugs. However, to what extent this translates into serum cholesterol levels in a real-life setting has not been systematically investigated.Objective: To estimate secular trends from 1994 to 2002 in blood lipid levels among unselected younger patients after a first acute myocardial infarction (AMI.Method: Descriptive single centre study using consecutive data collection in 781 patients (aged <65 years hospitalized with a first AMI during the period 1994–2002.Results: From 1994–2002, the use of lipid-lowering drugs increased from 10% to 94% for men and from 23% to 90% for women. In 1994, the mean serum cholesterol levels were 6.53 mmol/l in men and 6.32 mmol/l in women, decreasing to 4.31 mmol/l and 5.13 mmol/l in men and women, respectively, in 2002. Still, only 56% of the men and 35% of the women had total serum cholesterol levels <4.5 mmol/l in 2002.Conclusion: Despite a marked increase in lipid-lowering drug treatment in which there was an increase from about 10% in 1994 to more than 90% in 2002, current target levels of <4.5 mmol/l for serum cholesterol were not achieved in a significant proportion of post-AMI patients.Keywords: lipid levels, lipid-lowering medication, myocardial infarction, risk factors

The cholesterol-lowering effect of coconut flakes in humans with moderately raised serum cholesterol.

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Trinidad, Trinidad P; Loyola, Anacleta S; Mallillin, Aida C; Valdez, Divinagracia H; Askali, Faridah C; Castillo, Joan C; Resaba, Rosario L; Masa, Dina B

2004-01-01

This study investigated the effect of coconut flakes on serum cholesterol levels of humans with moderately raised serum cholesterol in 21 subjects. The serum total cholesterol of subjects differed and ranged from 259 to 283 mg/dL. The study was conducted in a double-blind randomized crossover design on a 14-week period, consisting of four 2-week experimental periods, with each experimental period separated by a 2-week washout period. The test foods were as follows: corn flakes as the control food, oat bran flakes as the reference food, and corn flakes with 15% and 25% dietary fiber from coconut flakes (made from coconut flour production). Results showed a significant percent reduction in serum total and low-density lipoprotein (LDL) cholesterol (in mg/dL) for all test foods, except for corn flakes, as follows: oat bran flakes, 8.4 +/- 1.4 and 8.8 +/- 6.0, respectively; 15% coconut flakes, 6.9 +/- 1.1 and 11.0 +/- 4.0, respectively; and 25% coconut flakes, 10.8 +/- 1.3 and 9.2 +/- 5.4, respectively. Serum triglycerides were significantly reduced for all test foods: corn flakes, 14.5 +/- 6.3%; oat bran flakes, 22.7 +/- 2.9%; 15% coconut flakes, 19.3 +/- 5.7%; and 25% coconut flakes, 21.8 +/- 6.0%. Only 60% of the subjects were considered for serum triglycerides reduction (serum triglycerides >170 mg/dL). In conclusion, both 15% and 25% coconut flakes reduced serum total and LDL cholesterol and serum triglycerides of humans with moderately raised serum cholesterol levels. Coconut flour is a good source of both soluble and insoluble dietary fiber, and both types of fiber may have significant role in the reduction of the above lipid biomarker. To our knowledge, this is the first study conducted to show a relationship between dietary fiber from a coconut by-product and a lipid biomarker. Results from this study serves as a good basis in the development of coconut flakes/flour as a functional food, justifying the increased production of coconut and coconut by-products.

Lipid reorganization induced by Shiga toxin clustering on planar membranes.

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Barbara Windschiegl

Full Text Available The homopentameric B-subunit of bacterial protein Shiga toxin (STxB binds to the glycolipid Gb(3 in plasma membranes, which is the initial step for entering cells by a clathrin-independent mechanism. It has been suggested that protein clustering and lipid reorganization determine toxin uptake into cells. Here, we elucidated the molecular requirements for STxB induced Gb(3 clustering and for the proposed lipid reorganization in planar membranes. The influence of binding site III of the B-subunit as well as the Gb(3 lipid structure was investigated by means of high resolution methods such as fluorescence and scanning force microscopy. STxB was found to form protein clusters on homogenous 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC/cholesterol/Gb(3 (65:30:5 bilayers. In contrast, membranes composed of DOPC/cholesterol/sphingomyelin/Gb(3 (40:35:20:5 phase separate into a liquid ordered and liquid disordered phase. Dependent on the fatty acid composition of Gb(3, STxB-Gb(3 complexes organize within the liquid ordered phase upon protein binding. Our findings suggest that STxB is capable of forming a new membrane phase that is characterized by lipid compaction. The significance of this finding is discussed in the context of Shiga toxin-induced formation of endocytic membrane invaginations.

Cholesterol metabolism and serum non-cholesterol sterols: summary of 13 plant stanol ester interventions.

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Hallikainen, Maarit; Simonen, Piia; Gylling, Helena

2014-04-27

The efficacy and safety of plant stanols added to food products as serum cholesterol lowering agents have been demonstrated convincingly, but their effects on cholesterol metabolism and on serum non-cholesterol sterols is less evaluated. The aim of this study was to assess the validity of serum non-cholesterol sterols and squalene as bioindices of cholesterol synthesis and absorption, and to examine how the individual serum non-cholesterol sterols respond to consumption of plant stanols. We collected all randomized, controlled plant stanol ester (STAEST) interventions in which serum cholestanol, plant sterols campesterol and sitosterol, and at least two serum cholesterol precursors had been analysed. According to these criteria, there was a total of 13 studies (total 868 subjects without lipid-lowering medication; plant stanol doses varied from 0.8 to 8.8 g/d added in esterified form; the duration of the studies varied from 4 to 52 weeks). Serum non-cholesterol sterols were assayed with gas-liquid chromatography, cholesterol synthesis with the sterol balance technique, and fractional cholesterol absorption with the dual continuous isotope feeding method. The results demonstrated that during the control and the STAEST periods, the serum plant sterol/cholesterol- and the cholestanol/cholesterol-ratios reflected fractional cholesterol absorption, and the precursor sterol/cholesterol-ratios reflected cholesterol synthesis. Plant sterol levels were dose-dependently reduced by STAEST so that 2 g of plant stanols reduced serum campesterol/cholesterol-ratio on average by 32%. Serum cholestanol/cholesterol-ratio was reduced less frequently than those of the plant sterols by STAEST, and the cholesterol precursor sterol ratios did not change consistently in the individual studies emphasizing the importance of monitoring more than one surrogate serum marker. Serum non-cholesterol sterols are valid markers of cholesterol absorption and synthesis even during cholesterol

More pistachio nuts for improving the blood lipid profile. Systematic review of epidemiological evidence.

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Lippi, Giuseppe; Cervellin, Gianfranco; Mattiuzzi, Camilla

2016-05-06

Recent evidence suggests that regular intake of nuts may be associated with reduction of all-cause mortality, especially cardiovascular deaths. Among all types of nuts, pistachio displays the most favorable dietary composition. Therefore, we searched Medline and ISI Web of Science to identify interventional studies which evaluated changes of conventional blood lipids after replacing part of normal caloric intake with pistachio nuts in humans. Overall, 9 studies were finally included in our systematical literature review (4 randomized crossover, 3 randomized controlled and 3 prospective). In 6/9 (67%) interventional studies total cholesterol and low-density lipoprotein cholesterol (LDL-C) decreased, whereas high-density lipoprotein cholesterol (HDL-C) increased. In all studies total cholesterol/HDL-C ratio (7/7; 100%) and LDL-C/HDL-C ratio (6/6; 100%) decreased after replacing caloric intake with pistachio nuts for not less than 3 weeks. A significant reduction of triglycerides could only be observed in 2 out of 8 studies (25%). Even more importantly, in no interventional study the intake of pistachio nuts was associated with unfavorable changes of the lipid profile. The results of our literature search provide solid evidence that intake of pistachio nuts may exerts favorable effects on the traditional blood profile, provided that their consumption does not increase the habitual or recommended daily caloric intake. It seems also reasonable to suggest that further studies aimed to investigate the favorable effects of nuts on human diseases should distinguish between one type and the others, since the different nuts exhibit unique dietary composition and may hence produce distinctive biological effects in humans.

Stratum Corneum Lipids: Their Role for the Skin Barrier Function in Healthy Subjects and Atopic Dermatitis Patients.

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van Smeden, Jeroen; Bouwstra, Joke A

2016-01-01

Human skin acts as a primary barrier between the body and its environment. Crucial for this skin barrier function is the lipid matrix in the outermost layer of the skin, the stratum corneum (SC). Two of its functions are (1) to prevent excessive water loss through the epidermis and (2) to avoid that compounds from the environment permeate into the viable epidermal and dermal layers and thereby provoke an immune response. The composition of the SC lipid matrix is dominated by three lipid classes: cholesterol, free fatty acids and ceramides. These lipids adopt a highly ordered, 3-dimensional structure of stacked densely packed lipid layers (lipid lamellae): the lateral and lamellar lipid organization. The way in which these lipids are ordered depends on the composition of the lipids. One very common skin disease in which the SC lipid barrier is affected is atopic dermatitis (AD). This review addresses the SC lipid composition and organization in healthy skin, and elaborates on how these parameters are changed in lesional and nonlesional skin of AD patients. Concerning the lipid composition, the changes in the three main lipid classes and the importance of the carbon chain lengths of the lipids are discussed. In addition, this review addresses how these changes in lipid composition induce changes in lipid organization and subsequently correlate with an impaired skin barrier function in both lesional and nonlesional skin of these patients. Furthermore, the effect of filaggrin and mutations in the filaggrin gene on the SC lipid composition is critically discussed. Also, the breakdown products of filaggrin, the natural moisturizing factor molecules and its relation to SC-pH is described. Finally, the paper discusses some major changes in epidermal lipid biosynthesis in patients with AD and other related skin diseases, and how inflammation has a deteriorating effect on the SC lipids and SC biosynthesis. The review ends with perspectives on future studies in relation to

Kefir consumption does not alter plasma lipid levels or cholesterol fractional synthesis rates relative to milk in hyperlipidemic men: a randomized controlled trial [ISRCTN10820810

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St-Onge, Marie-Pierre; Farnworth, Edward R; Savard, Tony; Chabot, Denise; Mafu, Akier; Jones, Peter JH

2002-01-01

Background Fermented milk products have been shown to affect serum cholesterol concentrations in humans. Kefir, a fermented milk product, has been traditionally consumed for its potential health benefits but has to date not been studied for its hypocholesterolemic properties. Methods Thirteen healthy mildly hypercholesterolemic male subjects consumed a dairy supplement in randomized crossover trial for 2 periods of 4 wk each. Subjects were blinded to the dairy supplement consumed. Blood samples were collected at baseline and after 4 wk of supplementation for measurement of plasma total, low-density lipoprotein, and high-density lipoprotein cholesterol and triglyceride concentrations, as well as fatty acid profile and cholesterol synthesis rate. Fecal samples were collected at baseline and after 2 and 4 wk of supplementation for determination of fecal short chain fatty acid level and bacterial content. Results Kefir had no effect on total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglyceride concentrations nor on cholesterol fractional synthesis rates after 4 wk of supplementation. No significant change on plasma fatty acid levels was observed with diet. However, both kefir and milk increased (p < 0.05) fecal isobutyric, isovaleric and propionic acids as well as the total amount of fecal short chain fatty acids. Kefir supplementation resulted in increased fecal bacterial content in the majority of the subjects. Conclusions Since kefir consumption did not result in lowered plasma lipid concentrations, the results of this study do not support consumption of kefir as a cholesterol-lowering agent. PMID:11825344

Variation of lipid and fatty acid compositions in Thai Perilla seeds grown at different locations

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Maitree Suttajit

2006-03-01

Full Text Available Perilla or Nga-Kee-Mon (Perilla frutescens seed has long been known as a rich source of α-linolenic acid (18:3, n-3. It is widely cultivated throughout Thailand. However, there are no data on the variation of lipid and fatty acid compositions among crops from different regions. The aim of this study was to examine the compositions of lipids and fatty acids in Thai perilla seed grown at different locations. Two different perilla seeds were harvested from Maehongsorn and Chiang Mai districts, and one commercial perilla was purchased from local market. Seeds were ground, lipid was extracted with chloroform: methanol (2:1, v/v and its composition determined by Iatroscan (TLC/FID. Fatty acid composition was analyzed with GLC using standard methods. Lipid content was between 34-36% (w/w. Triacylglycerol was a predominant lipid in perilla seed (97% of total lipids, and a minor component was phytosterol (3% of total lipids. The ratio of saturates: monounsaturates: polyunsaturates was approximately 1: 1: 8. Most predominant fatty acid was α-linolenic acid (18:3, n-3 (55-60% of total fatty acid. Seeds from Maehongsorn district had the highest concentration of α-linolenic acid, and commercial perilla had the lowest (P<0.05. Other two predominant fatty acids were linoleic acid (18:2, n-6 (18-22% of total fatty acid and oleic acid (18:1 (11-13% of total fatty acid. The results showed that the compositions of lipids and fatty acids in Thai perilla seeds varied significantly among samples from different locations.

Plasma lipid oxidation predicts atherosclerotic status better than cholesterol in diabetic apolipoprotein E deficient mice

DEFF Research Database (Denmark)

Petersen, Karen Ekkelund; Lykkesfeldt, Jens; Raun, Kirsten

2017-01-01

Increased levels of oxidative stress have been suggested to play a detrimental role in the development of diabetes-related vascular complications. Here, we investigated whether the concentration of malondialdehyde, a marker of lipid oxidation correlated to the degree of aortic plaque lesions...... in a proatherogenic diabetic mouse model. Three groups of apolipoprotein E knockout mice were studied for 20 weeks, a control, a streptozotocin-induced diabetic, and a diabetic enalapril-treated group. Enalapril was hypothesized to lower oxidative stress level and thus the plaque burden. Both diabetic groups were...... significantly different from the control group as they had higher blood glucose, HbA1c, total cholesterol, low-density lipoprotein, very low-density lipoprotein, together with a lower high-density lipoprotein concentration and body weight. Animals in the diabetic group had significantly higher plaque area...

Nonideal mixing in multicomponent lipid/detergent systems

International Nuclear Information System (INIS)

Tsamaloukas, Alekos; Szadkowska, Halina; Heerklotz, Heiko

2006-01-01

A detailed understanding of the mixing properties of membranes to which detergents are added is mandatory for improving the application and interpretation of detergent based protein or lipid extraction assays. For Triton X-100 (TX-100), a nonionic detergent frequently used in the process of solubilizing and purifying membrane proteins and lipids, we present here a detailed study of the mixing properties of binary and ternary lipid mixtures by means of high-sensitivity isothermal titration calorimetry (ITC). To this end the partitioning thermodynamics of TX-100 molecules from the aqueous phase to lipid bilayers composed of various mixtures of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), egg-sphingomyelin (SM), and cholesterol (cho) are characterized. Composition-dependent partition coefficients K are analysed within the frame of a thermodynamic model developed to describe nonideal mixing in multicomponent lipid/detergent systems. The results imply that POPC, fluid SM, and TX-100 mix almost ideally (nonideality parameters ρ α/β SM/cho ≤-6RT) and unfavourable PC/cho interactions (ρ PC/cho = 2RT) may under certain conditions cause POPC/TX-100-enriched domains to segregate from SM/cho-enriched ones. TX-100/cho contacts are unfavourable (ρ cho/TX = 4RT), so the system tends to avoid them. That means, addition of TX-100 promotes the separation of SM/cho-rich from PC/TX-100-rich domains. It appears that cho/detergent interactions are crucial governing the abundance and composition of detergent-resistant membrane patches

Adropin: An endocrine link between the biological clock and cholesterol homeostasis

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Sarbani Ghoshal