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Lipids and lipid oxidation with emphasis on cholesterol oxides in some Indian sweets available in London.

Ghee (clarified butter oil), a major ingredient in Indian sweets, is an important source of saturated fatty acids, cholesterol and cholesterol oxidation products (COP) that are considered risk factors for atherosclerosis. The high frequency of atherosclerotic complications reported among the Indian immigrants in England prompted determination of lipids and lipid oxidation status of a ghee sample and 15 Indian sweets available in London supermarkets. The fatty acid profile of the samples shows saturated fats (about 73%), mainly composed of myristic, palmitic and stearic acids, except in two samples. There were large variations in thio-barbituric acid reacting substance values (19-260 microg/100 g) and total COP (1.4-51.2 microg/g lipids) among the sweet samples. Regular consumption of some of these sweets can be a source of considerable amounts of saturated fatty acids, cholesterol and COP in the diet and may contribute to atherosclerosis.

Atherosclerosis↗

Comparison of the effect of lipid A analog E5531 and the lipid A from Escherichia coli on phospholipid membrane properties.

The effect of the lipid A analog E5531 on the phospholipid membrane was compared with that of the lipid A from Escherichia coli (EC). E5531 decreased the phase transition temperature of dipalmitoylphosphatidylcholine (DPPC) membrane and increased the fluidity and micropolarity. On the other hand, the effect of EC on the membrane was contradictory. These results suggested that the reason for the difference of biological effects of these two lipid A would be caused by the differences from the effect on the cell membranes.

Cell Membrane↗

Assessment of the protective potential of Premna tomentosa (L. Verbenaceae) extract on lipid profile and lipid-metabolizing enzymes in acetaminophen-intoxicated rats.

OBJECTIVES: The liver is often damaged by environmental toxins, poor eating habits, alcohol and over-the-counter drug use that damage and weaken the liver, leading to important public health problems such as hepatitis, cirrhosis, and alcoholic liver diseases. It is cardinal to treat liver disorders, because it affects the biochemistry of the cell directly. Damage to the liver can be prevented by including a balanced diet that includes nutrients and herbs that support a healthy liver. Premna tomentosa (PT) is one such herbal drug used widely in India for the treatment of liver disorders, and we have already reported the hepatoprotective potential and antioxidant property of methanolic extract of PT leaves. Because injury to the liver can promote a variety of reactions with consequent effect on lipids, the present study was designed to elucidate the hypolipidemic effect of PT extract in acetaminophen (AA)-induced hepatotoxicity in rats. DESIGN AND SUBJECTS: Animals were pretreated with PT extract (750 mg/kg, orally) for 15 days and then induced with hepatotoxicity by AA (640 mg/kg, intraperitoneally). RESULTS: PT extract pretreatment significantly inhibited induced alterations in the levels of cholesterol, triglycerides, free fatty acids, phospholipids, serum lipoproteins, and lipid-metabolizing enzymes. CONCLUSIONS: The results indicate that PT extract improves lipid metabolism and has the potential for use in hepatic disorders.

Acetaminophen↗

A vitamin E concentrate rich in tocotrienols had no effect on serum lipids, lipoproteins, or platelet function in men with mildly elevated serum lipid concentrations.

BACKGROUND: Tocotrienols, lipid-soluble antioxidants with vitamin E activity, have been reported to lower LDL-cholesterol concentrations and platelet aggregation in men, but results are contradictory. OBJECTIVE: To examine in detail the effects of a vitamin E concentrate rich in tocotrienols on serum lipoproteins and on platelet function in men at risk for cardiovascular disease. DESIGN: In this randomized, double-blind, placebo-controlled parallel trial, 20 men received daily for 6 wk 4 capsules, each containing 35 mg tocotrienols and 20 mg alpha-tocopherol; 20 other men received 4 capsules daily, each providing 20 mg alpha-tocopherol. All men had concentrations of serum total cholesterol between 6.5 and 8.0 mmol/L or lipoprotein(a) concentrations > 150 mg/L. RESULTS: Compliance was confirmed by changes in serum tocopherol and tocotrienol concentrations. Serum LDL cholesterol in the tocotrienol group was 4.80 mmol/L before and 4.79 mmol/L after intervention, and increased from 4.70 to 4.86 mmol/L in the placebo group (95% CI for the difference: -0.54, 0.19 mmol/L; P = 0.333). Also, changes in HDL cholesterol, triacylglycerol, lipoprotein(a), and lipid peroxide concentrations did not differ between the groups. After adjustment for differences in initial values, no effects were found on collagen-induced platelet aggregation velocity, maximum aggregation, or thromboxane B2 formation in citrated whole blood. ATP release, however, was lower in the tocotrienol group. Urinary thromboxane B2 and 11-keto-thromboxane B2 concentrations and coagulation and fibrinolytic measures did not change. CONCLUSION: The tocotrienol supplements used had no marked favorable effects on the serum lipoprotein profile or on platelet function in men with slightly elevated lipid concentrations.

Adenosine Triphosphate↗

Plasma lipids and lipoproteins in hypercholesterolemic men fed a lipid-lowering diet containing lean beef, lean fish, or poultry.

BACKGROUND: To reach desirable lipid and lipoprotein concentrations, patients with hypercholesterolemia are often told to replace the consumption of beef with that of fish and poultry. OBJECTIVE: The objective of this study was to compare the effects on lipoprotein profiles in hypercholesterolemic men of the incorporation of lean beef, poultry (without skin), and lean fish into an American Heart Association diet with a high polyunsaturated-to-saturated fatty acid ratio and a high fiber content. DESIGN: Three groups of subjects each rotated in a crossover design through 3 experimental periods that lasted 26 d each. The diets were planned to provide 11 713 kJ/d, of which 18% came from protein, 53% from carbohydrate, and 30% from lipids (polyunsaturated-to-monounsaturated-to-saturated fatty acid ratio: 1.0:1.1:1.0); 268 mg cholesterol/d; and 29 g fiber/d. RESULTS: The lean beef, lean fish, and poultry diets reduced plasma total and LDL cholesterol by 5-9%, LDL apolipoprotein B by 16-19%, VLDL triacylglycerols by 22-31%, and the ratio of total cholesterol to HDL cholesterol by 6-11%; they also increased the ratio of LDL cholesterol to apolipoprotein B by 18-28%. No significant difference was found in these lipid variables between the 3 experimental diets. However, the lean fish diet increased HDL(2) cholesterol significantly more (P < 0.05) than did the lean beef diet and the ratio of HDL(2) to HDL(3) cholesterol significantly more (P < 0.05) than did the lean beef and poultry diets. CONCLUSION: The results indicate that an American Heart Association diet with a high polyunsaturated-to-saturated fatty acid ratio and high fiber content induced numerous favorable changes in coronary artery disease risk factors in hypercholesterolemic men, regardless of the protein source.

Adult↗

Effects of medium-chain fatty acids and oleic acid on blood lipids, lipoproteins, glucose, insulin, and lipid transfer protein activities.

BACKGROUND: Dietary medium-chain fatty acids (MCFAs) are of nutritional interest because they are more easily absorbed from dietary medium-chain triacylglycerols (MCTs) than are long-chain fatty acids from, for example, vegetable oils. It has generally been claimed that MCFAs do not increase plasma cholesterol, although this claim is poorly documented. OBJECTIVE: We compared the effects of a diet rich in either MCFAs or oleic acid on fasting blood lipids, lipoproteins, glucose, insulin, and lipid transfer protein activities in healthy men. DESIGN: In a study with a double-blind, randomized, crossover design, 17 healthy young men replaced part of their habitual dietary fat intake with 70 g MCTs (66% 8:0 and 34% 10:0) or high-oleic sunflower oil (89.4% 18:1). Each intervention period lasted 21 d, and the 2 periods were separated by a washout period of 2 wk. Blood samples were taken before and after the intervention periods. RESULTS: Compared with the intake of high-oleic sunflower oil, MCT intake resulted in 11% higher plasma total cholesterol (P = 0.0005), 12% higher LDL cholesterol (P = 0.0001), 32% higher VLDL cholesterol (P = 0.080), a 12% higher ratio of LDL to HDL cholesterol (P = 0.002), 22% higher plasma total triacylglycerol (P = 0.0361), and higher plasma glucose (P = 0.033). Plasma HDL-cholesterol and insulin concentrations and activities of cholesterol ester transfer protein and phospholipid transfer protein did not differ significantly between the diets. CONCLUSIONS: Compared with fat high in oleic acid, MCT fat unfavorably affected lipid profiles in healthy young men by increasing plasma LDL cholesterol and triacylglycerol. No changes in the activities of phospholipid transfer protein and cholesterol ester transfer protein were evident.

Adult↗

Inhibition of lipid A- and lipopolysaccharide-induced cytokine secretion, B cell mitogenesis, and lethal shock by lipid A-specific murine monoclonal antibodies.

Three murine hybridomas secreting IgM monoclonal antibodies (MAbs) to lipid A (LA) of Salmonella minnesota R595 were generated. These MAbs serologically cross-reacted with LA and lipopolysaccharide (LPS) of unrelated gram-negative bacterial species. All three MAbs significantly suppressed the ability of LA and LPS from various gram-negative bacteria to induce tumor necrosis factor (TNF)-alpha (36%-67%) and interleukin-1 (30%-98%) in murine peritoneal macrophages and to stimulate B lymphocytes (37%-78%). Lipid A-induced TNF alpha production was also suppressed in mice (86%-88%). All three antibodies protected adrenalectomized mice against lethal shock induced by LA of S. minnesota R595. Optimal protection was achieved with one of the antibodies (MLA-1), if it was administered 2 h before injection of lipid A, and full protection persisted < or = 24 h. Moreover, MLA-1 was able to protect adrenalized or D(+)-galactosamine-sensitized mice against lethal shock induced by LPS derived from various gram-negative bacteria. This cross-protection could be predicted on the basis of serologic cross-reactivity and cross-neutralization by MLA-1 of the bioactivity of the heterologous LA or LPS in vitro.

Animals↗

The Collaborative Lipid Research Clinics Program Family Study. II. Response rates, representativeness of the sample, and stability of lipid and lipoprotein levels.

The Collaborative Family Study (1975-1978), the third phase of the Lipid Research Clinics Program Population Studies, covers 2405 probands and 15,693 of their relatives from nine North American communities. This sample was examined for participation differences across race, sex, locality, educational level, and reason for selection. The participation rates were somewhat lower for blacks, younger age groups, and subjects with lower educational levels. The probands' reason for selection into the study had little impact on the participation of probands or relatives. Moreover, based on information gathered at earlier examinations on eligible Family Study probands, the cornary risk factor profile appeared to be similar among participants and nonparticipants . The available longitudinal lipid data on probands indicated general consistency in lipid levels within subjects over short periods of time, in cholesterol even more so than in triglycerides. Among age strata, the younger subjects showed the least intrapersonal stability, especially for triglycerides.

Adolescent↗

Structural requirements of lipid A responsible for the functions: a study with chemically synthesized lipid A and its analogues.

To confirm the revised lipid A structure of Escherichia coli and to establish the structure responsible for its functions, biological activities of the synthetic compounds based on the presented structure of E. coli lipid A were investigated. Compound 506, 2-deoxy-6-O-(2-deoxy-2-[(R)-3-dodecanoyloxytetradecanoylamino]-3-O [(R)3-tetradecanoyloxytetradecanoyl]-beta-D-glucopyranosyl]-3-O-[(R) -3-hydroxytetradecanoyl]-2-[(R)-3-hydroxytetradecanoylamino]-alpha -D-glucopyranose 1,4'-bis(phosphate), exhibited activities identical to those of natural E. coli lipid A in eliciting Shwartzman reaction and tests on lethality, pyrogenicity, interferon- and tumor necrosis factor-inducing activities as well as in B-cell activating activity and Limulus amebocyte lysate gelating activity. With the exception of the Shwartzman reaction the monophosphorylated synthetic compounds at either the 1 or 4' position showed slightly lower activities than the compound with the bisphosphorylated compound (Compound 506). The compound without the phosphate group showed no or only very weak activities. The structural requirements for each activity (i.e. binding position and composition of fatty acids and presence of phosphate groups) are discussed taking into account the results of previous investigations.

Animals↗

The binding of maize DHN1 to lipid vesicles. Gain of structure and lipid specificity.

Dehydrins (DHNs; late embryogenesis abundant D-11) are a family of plant proteins induced in response to abiotic stresses such as drought, low temperature, and salinity or during the late stages of embryogenesis. Spectral and thermal properties of these proteins in purified form suggest that they are "intrinsically unstructured." However, DHNs contain at least one copy of a consensus 15-amino acid sequence, the "K segment," which resembles a class A2 amphipathic alpha-helical, lipid-binding domain found in other proteins such as apolipoproteins and alpha-synuclein. The presence of the K segment raises the question of whether DHNs bind lipids, bilayers, or phospholipid vesicles. Here, we show that maize (Zea mays) DHN DHN1 can bind to lipid vesicles that contain acidic phospholipids. We also observe that DHN1 binds more favorably to vesicles of smaller diameter than to larger vesicles, and that the association of DHN1 with vesicles results in an apparent increase of alpha-helicity of the protein. Therefore, DHNs, and presumably somewhat similar plant stress proteins in the late embryogenesis abundant and cold-regulated classes may undergo function-related conformational changes at the water/membrane interface, perhaps related to the stabilization of vesicles or other endomembrane structures under stress conditions.

Adaptation, Physiological↗

Insights into the role of specific lipids in the formation and delivery of lipid microdomains to the plasma membrane of plant cells.

The existence of sphingolipid- and sterol-enriched microdomains, known as lipid rafts, in the plasma membrane (PM) of eukaryotic cells is well documented. To obtain more insight into the lipid molecular species required for the formation of microdomains in plants, we have isolated detergent (Triton X-100)-resistant membranes (DRMs) from the PM of Arabidopsis (Arabidopsis thaliana) and leek (Allium porrum) seedlings as well as from Arabidopsis cell cultures. Here, we show that all DRM preparations are enriched in sterols, sterylglucosides, and glucosylceramides (GluCer) and depleted in glycerophospholipids. The GluCer of DRMs from leek seedlings contain hydroxypalmitic acid. We investigated the role of sterols in DRM formation along the secretory pathway in leek seedlings. We present evidence for the presence of DRMs in both the PM and the Golgi apparatus but not in the endoplasmic reticulum. In leek seedlings treated with fenpropimorph, a sterol biosynthesis inhibitor, the usual Delta(5)-sterols are replaced by 9beta,19-cyclopropylsterols. In these plants, sterols and hydroxypalmitic acid-containing GluCer do not reach the PM, and most DRMs are recovered from the Golgi apparatus, indicating that Delta(5)-sterols and GluCer play a crucial role in lipid microdomain formation and delivery to the PM. In addition, DRM formation in Arabidopsis cells is shown to depend on the unsaturation degree of fatty acyl chains as evidenced by the dramatic decrease in the amount of DRMs prepared from the Arabidopsis mutants, fad2 and Fad3+, affected in their fatty acid desaturases.

Arabidopsis↗

Dose-dependent effects of milk lipids on sex hormone and blood lipid levels in male mice.

Diets containing powdered whole milk caused a dose dependent increase in seminal vesicle weights when fed to 21 day old intact male mice. Blood cholesterol levels increased as the lipids in the diet increased. Triglyceride levels were high and inversely related to lipid intake. Peripheral androgen concentrations decreased as the lipid intake and seminal vesicle weights increased, indicating a possible shift of the hormone to the target organ tissue.

Administration, Oral↗

Conjugated linoleic acid evokes de-lipidation through the regulation of genes controlling lipid metabolism in adipose and liver tissue.

Conjugated linoleic acid (CLA) is a unique lipid that elicits dramatic reductions in adiposity in several animal models when included at < or = 1% of the diet. Despite a flurry of investigations, the precise mechanisms by which conjugated linoleic acid elicits its dramatic effects in adipose tissue and liver are still largely unknown. In vivo and in vitro analyses of physiological modifications imparted by conjugated linoleic acid on protein and gene expression suggest that conjugated linoleic acid exerts its de-lipidating effects by modulating energy expenditure, apoptosis, fatty acid oxidation, lipolysis, stromal vascular cell differentiation and lipogenesis. The purpose of this review shall be to examine the recent advances and insights into conjugated linoleic acid's effects on obesity and lipid metabolism, specifically focused on changes in gene expression and physiology of liver and adipose tissue.

Adipose Tissue↗

Primary cardiovascular events and serum lipid levels in elderly Japanese with hypercholesterolemia undergoing 6-year simvastatin treatment: a subanalysis of the Japan lipid intervention trial.

OBJECTIVES: To determine the relationship between serum lipid levels and the incidence of coronary events in older Japanese hypercholesterolemic patients without prior coronary heart disease (CHD). DESIGN: Post hoc subanalysis of the results in the Japan Lipid Intervention Trial. SETTING: A large-scale cohort observational study conducted throughout Japan. PARTICIPANTS: Men aged 35 to 70 and postmenopausal women younger than 70 with serum total cholesterol (TC) level of 220 mg/dL or greater treated for 6 years with low-dose simvastatin (52,421 total patients). After exclusion of 5,127 patients because of prior CHD and 4,934 patients because of incomplete data, 42,360 patients were divided into an older (9,860 patients, aged 65-70, mean age 67.1) and younger (32,500 patients, younger than 65, mean age 54.9) group and analyzed. MEASUREMENTS: Fasting serum lipid levels were measured every 6 months. Major coronary events, including fatal or nonfatal myocardial infarction, and sudden cardiac death as the primary endpoint and other cardiovascular diseases, including onset of angina pectoris, cerebrovascular events, and any causes of death, as the secondary endpoints were monitored. RESULTS: Simvastatin treatment in older patients was as safe and effective as in younger patients. Incident rates of major coronary events were 1.30 per 1,000 patient-years in the older group and 0.80 per 1,000 patient-years in the younger group. The incidence of a major coronary event was correlated to serum TC and low-density lipoprotein cholesterol (LDL-C) levels in both groups. The absolute risk of major coronary events in the older group was higher than in the younger group at any level of LDL-C, whereas the relative risk increased by 1.7% with an elevation of each 1 mg/dL LDL-C level in both groups. In the older group, the risk of major coronary events also increased as triglyceride level increased, whereas the risk decreased as high-density lipoprotein cholesterol level increased above 60 md/dL. CONCLUSION: The LDL-C level-dependent increase of relative risk of CHD was similar in elderly and younger patients, whereas the absolute risk at any LDL-C level in elderly patients was higher than in younger patients.

Adult↗

Lipid accumulation, lipid body formation, and acyl coenzyme A oxidases of the yeast Yarrowia lipolytica.

Yarrowia lipolytica contains five acyl-coenzyme A oxidases (Aox), encoded by the POX1 to POX5 genes, that catalyze the limiting step of peroxisomal beta-oxidation. In this study, we analyzed morphological changes of Y. lipolytica growing in an oleic acid medium and the effect of POX deletions on lipid accumulation. Protrusions involved in the uptake of lipid droplets (LDs) from the medium were seen in electron micrographs of the surfaces of wild-type cells grown on oleic acid. The number of protrusions and surface-bound LDs increased during growth, but the sizes of the LDs decreased. The sizes of intracellular lipid bodies (LBs) and their composition depended on the POX genotype. Only a few, small, intracellular LBs were observed in the mutant expressing only Aox4p (Deltapox2 Deltapox3 Deltapox5), but strains expressing either Aox3p or both Aox3p and Aox4p had the same number of LBs as did the wild type. In contrast, strains expressing either Aox2p or both Aox2p and Aox4p formed fewer, but larger, LBs than did the wild type. The size of the LBs increased proportionately with the amount of triacylglycerols in the LBs of the mutants. In summary, Aox2p expression regulates the size of cellular triacylglycerol pools and the size and number of LBs in which these fatty acids accumulate.

Acyl-CoA Oxidase↗

Immunobiologically active lipid A analogs synthesized according to a revised structural model of natural lipid A.

Synthetic lipid A analogs which have two amide-bound and two ester-bound (R)-3-hydroxytetradecanoyl groups at the C-2 and -2' and C-3 and -3' positions of beta(1-6)glucosamine disaccharide mono- or diphosphates showed high activities in most in vitro assays, and the lethality of a diphosphate derivative to galactosamine-treated mice was almost comparable to that of natural lipid A. The pyrogenicity and Shwartzman induction activity of the synthetic analogs, however, were much less than those of natural lipid A.

Adult↗

Protection of mice from lethal endotoxemia by use of an ornithine-containing lipid or a serine-containing lipid.

The effects of an ornithine-containing lipid [alpha-N-(3-acyloxyacyl)-ornithine (Orn-L)] or a serine-containing lipid [alpha-N-(3-acyloxyacyl)-serine (Ser-L)] from Flavobacterium meningosepticum on lethal endotoxemia in mice were examined. When 500 micrograms of Orn-L was intravenously administered 1 h before intravenous administration of a lethal dose of endotoxin, none of the mice died. The protective effect of Ser-L was weaker than that of Orn-L. Light and electron microscopic studies demonstrated that necrosis of hepatocytes caused by endotoxin was prevented by pretreatment with Orn-L. Furthermore, Kupffer cells were activated morphologically 1 h after the administration of Orn-L or Ser-L, and the liposomes of the lipoamino acids were incorporated into phagolysosomes in activated Kupffer cells. The activity of tumor necrosis factor in sera of endotoxin-treated mice was decreased markedly by pretreatment of mice with Orn-L. In vitro, the lipoamino acids suppressed endotoxin-induced tumor necrosis factor generation but did not suppress tumor necrosis factor generation induced by zymosan and whole cells of Staphylococcus aureus. These results suggested that Orn-L and Ser-L can be used as specific blocking agents against endotoxin. The blocking mechanism may be antagonistic, because of the structural similarities between the lipoamino acids and endotoxin lipid A.

Animals↗

Lipids of the Spirochaetales: comparison of the lipids of several members of the genera Spirochaeta, Treponema, and Leptospira.

The lipid compositions of 17 spirochetes belonging to the genera Spirochaeta and Treponema were investigated and compared with data previously derived from 11 strains of Leptospira. The lipid compositions and lipid metabolism of any of these genera is sufficiently different to be characteristic of that genus and to differentiate it from the other two genera. Members of the genus Leptospira are characterized by their ability to beta-oxidize long chain fatty acids as their major carbon and energy source. With few exceptions, they are incapable of synthesizing fatty acids de novo. The major phospholipid found was phosphatidyl ethanolamine. No glycolipid or phosphatidyl choline was found in these organisms. Members of the genus Treponema studied were incapable of beta-oxidation as well as de novo synthesis of fatty acids. Phosphatidyl choline is the major phospholipid of this genus. The glycolipid, monogalactosyl diglyceride, is a major component of the Treponema. Members of the Spirochaeta did synthesize fatty acids de novo. Although these spirochetes contain a monoglycosyl diglyceride, the hexose content of the glycolipid varied from species to species. Neither phosphatidyl ethanolamine nor phosphatidyl choline was found in the Spirochaeta.

Chromatography, Gas↗