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Lipid metabolic studies in oophorectomised women: effects on serum lipids and lipoproteins of three synthetic progestogens.

Norethisterone acetate, medroxyprogesterone acetate and levonorgestrel were administered to oophorectomised women to evaluate the effects they have on lipid metabolism. Blood samples were drawn after a 3 wk period without hormone therapy and after 3 wk on each progestogen. Serum and lipoprotein lipids were followed and an oral glucose tolerance test with blood glucose and plasma insulin determinations were performed. The nortestosterone derivatives, norethisterone acetate and levonorgestrel, decreased high density lipoprotein cholesterol as well as alpha-lipoproteincholesterol, while the 17-hydroxyprogesterone derivative medroxyprogesterone acetate did not. Norethisterone acetate and medroxyprogesterone acetate impaired glucose tolerance. A difference between nortestosterone derivatives and 17-hydroxyprogesterone derivatives having an effect on high density lipoproteins is suggested.

Adult↗

Lipids and lipid peroxidation products in the pathogenesis of age-related macular degeneration.

In people over 50, age-related macular degeneration (ARMD) has become the most common cause for severe visual loss and legal blindness in all industrialized nations. Currently, there is no effective treatment for the majority of patients. To develop new and effective modes of therapy, understanding of the molecular basis of the disease in mandatory. However, the pathogenesis of ARMD is still poorly understood. Several lines of evidence suggest that aging changes of the retinal pigment epithelium (RPE), in particular the accumulation of autofluorescent lipofuscin granules in the lysosomal compartment of postmitotic RPE cells, play a key role in the pathogenesis of the disease. Recent studies indicate that lipidic compounds of lipofuscin, represented by the retinoid A2-E, and protein damage by lipid peroxidation products, in particular malondialdehyde and 4-hydroxynonenal, induce lysosomal dysfunction and lipofuscinogenesis in the RPE. The possible mechanisms underlying this lysosomal dysfunction and the resulting adverse effects on overall RPE function are discussed.

Age Factors↗

Effect of smoking on lipid profile, lipid peroxidation and antioxidant status in normal subjects and in patients during and after acute myocardial infarction.

We studied changes in lipid peroxidation, vitamin E status and lipid profile due to smoking in healthy subjects, patients with acute myocardial infarction (MI), and in stabilized patients surviving MI. A significant increase in malondialdehyde (MDA) concentrations was observed in MI patients, more than in smokers (P<0.05), as compared to control. The plasma vitamin E as well as the ratio of vitamin E/lipids were significantly lower in MI patients as compared to stable ischemic heart disease (IHD) patients and controls. Our data show that smoking is associated with lowered antioxidant status in MI.

Adult↗

Lipid peroxidation in skeletal muscle of obese as compared to endurance-trained humans: a case of good vs. bad lipids?

Intra-myocellular triglycerides (IMTG) accumulate in the muscle of obese and endurance-trained (ET) humans and are considered a pathogenic factor in the development of insulin resistance, in the former. We postulate that this paradox may be associated with the peroxidation status of the IMTG. IMTG content was the same in the obese and ET subjects. The lipid peroxidation/IMTG ratio was 4.2-fold higher in the obese subjects. Hence, obesity results in an increased level of IMTG peroxidation while ET has a protective effect on IMTG peroxidation. This suggests a link between the lipid peroxidation/IMTG ratio and insulin resistance.

Adult↗

The lipid-containing bacteriophage PR4. Effects of altered lipid composition on the virion.

Phage PR4 was grown on a variety of Escherichia coli mutants defective in fatty acid and phospholipid metabolism. The composition of the phage lipids was modified by changing the composition of the host membrane phospholipids. The compositions of both the polar and the acyl moieties of the phospholipids were altered. The proportion of saturated fatty acids in the phage phospholipids was increased in increments from 44% of the total fatty acids to 55%, 61% and 69% of the total fatty acids using a host mutant with a temperature-sensitive defect in unsaturated fatty acid biosynthesis. The increase in saturated fatty acids led to a pronounced loss of infectivity when the phage were incubated at temperatures between 2 degrees C and 30 degrees C (temperatures below those at which the phage were grown). The greater the level of saturated fatty acids in the phage phospholipids, the higher the temperature below which the phage were inactivated. Our results strongly suggest that the phage membrane undergoes a lipid phase transition, which can disrupt and inactivate the virion. The phospholipid composition of PR4 was also altered by using host mutants defective in phosphatidylethanolamine and/or cardiolipin synthesis. Phage PR4 grown on wild-type host strains contains 56% phosphatidylethanolamine, 37% phosphatidylglycerol, 4.6% cardiolipin and no detectable phosphatidylserine. However, in response to changes in the host, PR4 preparations were obtained with phospholipid compositions varying from 28% to 60% in phosphatidylethanolamine, from 22% to 39% in phosphatidylglycerol, from 1% to 15% in cardiolipin and containing as much as 35% phosphatidylserine. These changes in phospholipid composition did not affect the infectivity of the phage. Moreover, the increased level of phosphatidylglycerol in the phage relative to the host was not altered by these manipulations. It is concluded that the net charge of the phage membrane phospholipids is not involved in the selection or function of the viral phospholipids. We also present evidence suggesting that the phage and host membranes do not fuse during the course of infection.

Cold Temperature↗

Lipid composition in atheromatous plaque: evaluation of the lipid three-phase percentage.

There is a renewed interest in the study of plaque lipid composition because it is recognized that it, rather than the luminal narrowing, influences the plaque stability and determines patient symptoms. At this purpose, we quantitatively evaluated in the carotid plaque of different categories of patients the expression of triglycerides, phospholipids, cholesterol, free cholesterol, esters of cholesterol, and the percentages of the three-phases (cholesterol, esters of cholesterol, phospholipids) by using the "Roozeboom triangle". Significant differences in the content of specific lipid and the percentage of the three-phases were detected among the different types of plaque evaluated in this study. The analysis of the three-phases by "Roozeboom triangle" may open a new approach in the study of atheromatous plaque and give new information on development of the disease.

Aged↗

Gentamicin induced dose related alterations in lipid levels and lipid peroxidation in central auditory pathway of the rat.

A study was carried out on the effect of gentamicin on the central auditory pathway in rats. Rats were administered graded doses of gentamicin (60 mg, 100 mg and 160 mg/kg b.wt., i.m.) daily for 21 days. Levels of total lipids, phospholipids and cholesterol showed dose related increment in the central auditory pathway. On the other hand, the rate of lipid peroxidation was inhibited in all regions of the central auditory pathway of the rat.

Animals↗

Lipid chain motion in an interdigitated gel phase: conventional and saturation transfer ESR of spin-labeled lipids in dipalmitoylphosphatidylcholine-glycerol dispersions.

The lipid chain dynamics in the interdigitated gel phase of dipalmitoylphosphatidylcholine (DPPC) dispersed in glycerol and in the fully hydrated noninterdigitated gel phase in aqueous buffer were compared by using conventional and saturation transfer electron spin resonance (ESR) spectroscopy. Twelve different positional isomers of phosphatidylcholine spin-labeled in the sn-2 chain were used to characterize the chain motion. The outer hyperfine splittings of the conventional ESR spectra and the line height ratios at the diagnostic spectral positions in the saturation transfer ESR spectra were taken as indices of the rotational mobility of the labeled chain segments in the gel phase (0-40 degrees C). The conventional spin label ESR spectra revealed a gradient of increasing mobility on proceeding down the chain toward the terminal methyl end in the fully hydrated DPPC gel phase bilayer structure. This gradient was absent in the interdigitated gel phase, i.e., the rotational mobility throughout the length of the lipid chain was comparable to that near the polar interface, on the conventional ESR time scale. Values of the outer hyperfine splitting for spin labels at the 5- and 14-C atom positions in the chain were 65.5 and 61.0 G in buffer, respectively, and 67.0 G for both positions in glycerol, at 0 degrees C. At 35 degrees C, still in the gel phase, these differences between the two systems were much greater. Saturation transfer ESR measurements revealed that the motion throughout the chain was restricted on the microsecond time scale in the interdigitated phase.(ABSTRACT TRUNCATED AT 250 WORDS)

1,2-Dipalmitoylphosphatidylcholine↗

Effects of alpha-tocopherol, beta-carotene, and soy isoflavones on lipid oxidation of structured lipid-based emulsions.

Structured lipids (SLs) are triacylglycerols that have been modified to change the fatty acid composition and/or positional distribution in the glycerol backbone by chemically and/or enzymatically catalyzed reactions and/or genetic engineering. Ten percent oil-in-water emulsions were formulated with a canola oil/caprylic acid SL and stabilized with 0.5% whey protein isolate (WPI) or sucrose fatty acid ester (SFE). The effects of alpha-tocopherol, beta-carotene, genistein, and daidzein (added at 0.02 wt % of oil) on lipid oxidation were evaluated over a 15-day period in emulsion samples. Significantly (p < 0.05) less total oxidation (calculated from peroxide value and anisidine value measurements) occurred in the WPI emulsions compared to their SFE counterparts. In this study, alpha-tocopherol, beta-carotene, and both soy isoflavones exhibited prooxidant activities in SFE emulsions. Because of their ability to exhibit prooxidant activity under certain conditions, manufacturers must experiment with these compounds before adding them to SL-based products as functional ingredients.

Antioxidants↗

Reduction of ubiquinone in membrane lipids by rat liver cytosol and its involvement in the cellular defence system against lipid peroxidation.

Rat liver homogenates reduced ubiquinone (UQ)-10 to ubiquinol (UQH2)-10 in the presence of NADPH rather than NADH. This NADPH-dependent UQ reductase (NADPH-UQ reductase) activity that was not inhibited by antimycin A and rotenone, was located mainly in the cytosol fraction and its activity accounted for 68% of that of the homogenates. Furthermore, the NADPH-UQ reductase from rat liver cytosol efficiently reduced both UQ-10 incorporated into egg yolk lecithin liposomes, and native UQ-9 residing in rat microsomes, to the respective UQH2 form in the presence of NADPH. The gross redox ratios of UQH2-9/(UQ-9 + UQH2-9) in individual tissues of rat correlated positively with the log of their respective cytosolic NADPH-UQ reductase activities, while the redox ratios in every intracellular fraction from liver were at about the same level, irrespective of NADPH-UQ reductase activities in the respective fractions. The combined addition of rat liver cytosol and NADPH inhibited to a great extent 2,2'-azobis(2,4-dimethyl-valeronitrile)-induced lipid peroxidation of UQ-10-fortified lecithin liposomes and completely inhibited such peroxidation in the liposomes in which UQH2-10 replaced UQ-10. The NADPH-UQ reductase activity was clearly separated from DT-diaphorase (EC 1.6.99.2) activity by means of Cibacron Blue-immobilized Bio-Gel A-5m chromatography. In conclusion, the NADPH-UQ reductase in cytosol, which is a novel enzyme to our knowledge, was presumed to be responsible for maintaining the steady-state redox levels of intracellular UQ and thereby to act as an endogenous antioxidant in protecting intracellular membranes from lipid peroxidation that is inevitably induced in aerobic metabolism.

Animals↗

Influence of hydrocortisone acetate administered to the lactating rat on lipid composition of the milk and serum lipid levels in dams and pups.

The influence of i.m. administration of hydrocortisone acetate to the mother (doses of 0.4, 0.8 or 2 mg/100 g body weight/day) during the first 15 days of lactation on milk composition in fatty acids mother and pups serum levels of lipids and their effect on pups' growth is studied. Serum levels of cholesterol and triglycerides in mothers increase at any of the experimental doses. Daily injections of 2 mg/100 g bw to the mother cause an increase in the percentage of C16 as well as in the level of fatty acids derived from linoleic and linolenic acids while reducing the percentage of C18:1. The treatment brings about a higher level in total lipids in the milk which is proportional to the dose. Doses of 0.4 and 0.8 mg increase the percentage of C8 and C10, while the dose of 2 mg enhances the % of C16. A fall in the uptake of linoleic acid by the mammary gland is observed when using any of the experimental doses. No change is observed either in the weight of pups or in serum cholesterol levels while triglyceride level is increased by the effect of treatment. The higher dose increases the level of linolenic acid and some of its derivates.

Animals↗

Fatty acid composition of phospholipids and neutral lipids and lipid peroxidation in human breast cancer and lipoma tissue.

Since unsaturated fatty acids have been shown to control cell division experimentally the fatty acid composition in human mammary cancers as compared with the healthy surrounding tissue was studied. Both phospholipid and neutral lipid fractions were extracted for study and further lipid peroxidation expressed as thiobarbituric acid reactive substances was measured. For a comparison a benign adipose tissue tumor, lipoma, was studied. There was a 3.6-fold increase in phospholipid contents of cancer as compared with a reference tissue. No such differences were observed between lipoma and surrounding adipose tissue. In the phospholipid fatty acids of mammary cancers there was a marked increase in the relative amounts of unsaturated fatty acids, especially arachidonic acid, while saturated fatty acids were decreased, as compared with a healthy reference breast tissue or lipomas. The data suggest that the fatty acids might have a role in the development of breast cancer, possibly related to the formation of reactive metabolites of unsaturated fatty acids in the initiation of cancer or to their promotional effects.

9,10-Dimethyl-1,2-benzanthracene↗

Lipids and lipoproteins in a young adult population. The Beaver County Lipid Study.

Though atherosclerosis may have its origins in childhood, intervention studies on coronary heart disease risk factors have usually begun in older adults. Whether young adults exhibit similar relationships of lifestyle to coronary heart disease risk factors, and therefore might be suitable candidates for appropriate intervention, is poorly understood. The Beaver County Lipid Study is a 9-year follow-up study of a free-living young adult population (mean age 22 years) who were initially screened for hypercholesterolemia as seventh grade school children. This report focuses upon cross-sectional correlates of lipid and lipoprotein concentrations in 561 individuals (males n = 262; females n = 299) in 1981-1982. Body mass index was positively related to low density lipoprotein (LDL) cholesterol and triglycerides in men (r = 0.21; p less than 0.001 and r = 0.41; p less than 0.001) and women (r = 0.16; p less than 0.001 and r = 0.20; p less than 0.001). Cigarette smoking was inversely associated with high density lipoprotein (HDL) cholesterol in men (r = -0.11; p less than 0.001) and women (r = -0.20; p less than 0.001) but positively related to triglycerides in both sexes (r = 0.10; p = 0.05 for men and r = 0.19; p less than 0.01 for women). Alcohol consumption was positively related to HDL cholesterol and triglycerides only among men (r = 0.19; p less than 0.001 and r = 0.12; p less than 0.05, respectively). Educational achievement was also positively related to HDL cholesterol in men (p less than 0.01) and women (p less than 0.001). Multivariate analyses indicate that the sex difference in LDL cholesterol was largely eliminated by controlling for body mass index while significant sex differences in both HDL cholesterol and triglycerides remained after controlling for covariates. Results suggest that the known associations in older adults of body mass index and health-related behavior with lipoproteins are well established by young adulthood. Early intervention particularly for obesity may help ameliorate some of the male excess in cardiovascular disease risk.

Adult↗

Increased pigment and lipid content, lipid variety, and cell and population size of the microalgae Chlorella spp. when co-immobilized in alginate beads with the microalgae-growth-promoting bacterium Azospirillum brasilense.

Three strains of the freshwater microalgae used for wastewater treatment, Chlorella vulgaris and Chlorella sorokiniana co-immobilized separately in alginate beads with the microalgae-growth-promoting bacterium Azospirillum brasilense Cd, resulted in significant changes in microalgal-population size, cell size, cell cytology, pigment, lipid content, and the variety of fatty acids produced in comparison with microalgae immobilized in alginate without the bacterium. Cells of C. vulgaris UTEX 2714 did not change in size, but the population size within the beads significantly increased. On the other hand, C. vulgaris UTEX 395 cells grew 62% larger, but their numbers did not increase. The population of C. sorokiniana UTEX 1602 increased, but not their cell size. The content of pigments chlorophyll a and b, lutein, and violoaxanthin increased in all microalgal species. The lipid content also significantly increased in all three strains, and the number of different fatty acids in the microalgae increased from four to eight. This study indicates that the microalgae-growth-promoting bacterium induced significant changes in the metabolism of the microalgae.

Alginates↗

Comparison between swallowing and chewing of garlic on levels of serum lipids, cyclosporine, creatinine and lipid peroxidation in renal transplant recipients.

Hyperlipidemia and increased degree of oxidative stress are among the important risk factors for Atherosclerosis in renal transplant recipients (RTR). The Medical treatment of hyperlipidemia in RTR because of drugs side effects has been problematic, therefore alternative methods such as using of Garlic as an effective material in cholesterol lowering and inhibition of LDL Oxidation has been noted. For evaluation of garlic effect on RTR, 50 renal transplant patients with stable renal function were selected and divided into 2 groups. They took one clove of garlic (1 gr) by chewing or swallowing for two months, after one month wash-out period, they took garlic by the other route. Results indicated that although lipid profile, BUN, Cr, serum levels of cyclosporine and diastolic blood pressure did not change, Systolic blood pressure decreased from 138.2 to 132.8 mmHg (p=0.001) and Malondialdehyde (MDA) decreased from 2.4 to 1.7 nmol/ml (p=0.009) by swallowing route, Cholesterol decreased from 205.1 to 195.3 mg/dl (p=0.03), triglyceride decreased from 195.7 to 174.8 mg/dl (p=0.008), MDA decreased from 2.5 to 1.6 nmol/ml (p=0.001), systolic blood pressure decreased from 137.5 to 129.8 mmHg (p=0.001), diastolic blood pressure decreased from 84.6 to 77.6 mmHg (p=0.001) and Cr decreased from 1.51 to 1.44 mg/dl (p=0.03) by chewing route too. However HDL, LDL and cyclosporine serum levels had no significant differences by both of swallowing and chewing routes. We conclude that undamaged garlic (swallowed) had no lowering effect on lipid level of serum. But Crushed garlic (chewed) reduces cholesterol, triglyceride, MDA and blood pressure. Additionally creatinine reduced without notable decrease in cyclosporine serum levels may be due to cyclosporine nephrotoxicity ameliorating effect of garlic.

Adult↗

Dietary sodium chloride restriction enhances aortic wall lipid storage and raises plasma lipid concentration in LDL receptor knockout mice.

This study aimed at measuring the influence of a low salt diet on the development of experimental atherosclerosis in moderately hyperlipidemic mice. Experiments were carried out on LDL receptor (LDLR) knockout (KO) mice, or apolipoprotein E (apoE) KO mice on a low sodium chloride diet (LSD) as compared with a normal salt diet (NSD). On LSD, the rise of the plasma concentrations of TG and nonesterified fatty acid (NEFA) was, respectively, 19% and 34% in LDLR KO mice, and 21% and 35% in apoE KO mice, and that of plasma cholesterol was limited to the LDLR KO group alone (15%). Probably due to the apoE KO severe hypercholesterolemia, the arterial inner-wall fat storage was not influenced by the diet salt content and was far more abundant in the apoE KO than in the LDLR KO mice. However, in the less severe hypercholesterolemia of the LDLR KO mice, lipid deposits on the LSD were greater than on the NSD. Arterial fat storage correlated with NEFA concentrations in the LDLR KO mice alone (n = 14, P = 0.0065). Thus, dietary sodium chloride restriction enhances aortic wall lipid storage in moderately hyperlipidemic mice.

Animals↗

Selenium-induced alteration of lipids, lipid peroxidation, and thiol group in circadian rhythm centers of rat.

The effect of sodium selenite (0.05, 0.1, and 0.2 mg/kg body weight, ip) on the contents of lipids (phospholipids, cholesterol, esterified fatty acids, gangliosides), thiobarbituric acid reactive substance (TBARS), and thiol group in circadian rhythm centers (preoptic area, brainstem, and posterior hypothalamus) of male Wistar rats was studied after 7 d of treatment. The content of phospholipids was elevated significantly with a dose of 0.1 mg/kg of selenite in the preoptic area and brainstem, but a 0.2-mg/kg dose has depleted its level significantly in these regions. The alteration of phospholipids in posterior hypothalamus was not significant with three doses of sodium selenite. The level of cholesterol in the preoptic area was inhibited significantly with a dose of 0.05 mg/kg sodium selenite, but its level was elevated significantly with a dose of 0.2 mg/kg selenite in the preoptic area and brainstem. Alteration with three doses of sodium selenite in the posterior hypothalamus was not significant. The ganglioside level in the preoptic area and brainstem was elevated significantly with a 0.1-mg dose of sodium selenite; conversely, a 0.2 mg dose of sodium selenite caused a significant depletion on its content in these areas. In the posterior hypothalamus, the ganglioside level was depleted significantly with a dose of 0.1 mg, but elevated significantly with a dose of 0.2 mg of sodium selenite. The level of esterified fatty acids was decreased significantly in the preoptic area and brainstem with a dose of 0.1 mg/kg sodium selenite, but in these regions, its level was elevated with a dose of 0.2 mg/kg sodium selenite and its elevation was significant in the preoptic area. In the posterior hypothalamus, the alteration of esterified fatty acids with three doses of sodium selenite was not significant. The effect of 0.1 and 0.2 mg/kg sodium selenite on the TBARS level and thiol group in sleep centers was significantly opposite to the wakefulness center. A sodium selenite dose of 0.1 mg/kg had depleted the content of TBARS in the preoptic area and brainstem but elevated the content of the thiol group significantly in the posterior hypothalamus. On the other hand, a 0.2-mg/kg dose of sodium selenite has significantly elevated the content of TBARS but depleted the content of the thiol group significantly in the posterior hypothalamus. No dose-dependent alteration was observed on the content of lipids, TBARS, and thiol group in the circadian rhythm centers of rats.

Animals↗

Effects of intravenous and dietary lipid challenge on intramyocellular lipid content and the relation with insulin sensitivity in humans.

An increased intramyocellular lipid (IMCL) content, as quantified by (1)H-magnetic resonance spectroscopy ((1)H-MRS), is associated with reduced insulin sensitivity. At present, it is unclear which factors determine IMCL formation and how rapidly IMCL accumulation can be induced. We therefore studied the impact of hyperinsulinemia and elevated circulating nonesterified fatty acid (NEFA) levels on IMCL formation and insulin sensitivity. We further evaluated the influence of a high-fat diet on IMCL storage. In the infusion protocol, 12 healthy male subjects underwent a 6-h hyperinsulinemic-euglycemic glucose clamp with concomitant infusion of Intralipid plus heparin. IMCL was quantified by (1)H-MRS in soleus (SOL) and tibialis anterior (TA) muscle at baseline and then every hour. IMCL levels started to increase significantly after 2 h, reaching a maximum of 120.8 +/- 3.4% (SOL) and 164.2 +/- 13.8% (TA) of baseline after 6 h (both P < 0.05). In parallel, the glucose infusion rate (GIR) decreased progressively, reaching a minimum of 60.4 +/- 5.4% of baseline after 6 h. Over time, the GIR was strongly correlated with IMCL in TA (r = -0.98, P < or = 0.003) and SOL muscle (r = -0.97, P < or = 0.005). In the diet protocol, 12 male subjects ingested both a high-fat and low-fat diet for 3 days each. Before and after completion of each diet, IMCL levels and insulin sensitivity were assessed. After the high-fat diet, IMCL levels increased significantly in TA muscle (to 148.0 +/- 16.9% of baseline; P = 0.005), but not in SOL muscle (to 114.4 +/- 8.2% of baseline; NS). Insulin sensitivity decreased to 83.3 +/- 5.6% of baseline (P = 0.033). There were no significant changes in insulin sensitivity or IMCL levels after the low-fat diet. The effects of the high-fat diet showed greater interindividual variation than those of the infusion protocol. The data from the lipid infusion protocol suggest a functional relationship between IMCL levels and insulin sensitivity. Similar effects could be induced by a high-fat diet, thereby underlining the physiological relevance of these observations.

Adult↗