Effect of alpha-tocopherol and phospholipids with omega-3 fatty acids on membrane properties

As a result of the investigations conducted it was displayed, that alpha-tocopherol and phospholipids including into their composition omega-3-acids, differed in their influencing the composition of heart microsomes membranes lipids. The insufficient quantity of vitamin E in the animals ration was defined as leading to the cardiac microsomes lisophospholipids (lisophosphatidylcholin, lisophospatidylethanolamin), diphosphatidylglycerol increase as well as to the tendency to sphingomyeline and phosphatidylethanolamin decrease. While administrating both alpha-tocopherol and the complex of phospholipids with omega-3-fatty acids, the correction of the phospholipids composition microsomes membranes is observed as tending towards their stabilization, however the marine phospholipids complex is more active than alpha-tocopherol. Administration of phospholipids with omega-3-fatty acids during the period of 30 days provided for the increase of relationship: polyunsaturated fatty acids to saturated fatty acids in the cardiac microsomal membranes, evidencing about increasing the unsaturated cellular membranes. While administrating the phospholipids, into the cardiac microsomes the eicozepentaenic acid was identified, failing to be in the norm, docozahexaenic acid content increased. The results obtained testify, that at the pathology there are changes in the quantitative relationship of membrane phospholipids and fatty acids, being a result of changing the biomembranes permeability as well as their functions disturbances. The adverse effect of E-deficiency to the membrane structure was revealed as capable to be regulated by the marine phospholipid complex, including omega-3-fatty acids.     

Effect of "marine" phospholipids omega-3 fatty acids on the composition of fatty acids of rat liver microsomal membrane under oxidative stress

As a result of experiments conducted the marine phospholipids preparation enriched by omega-3 fatty acids was defined to modify fatty acids content due to changes of fatty acids level change in the neutral lipids and phospholipids fractions. As well it was identified, that at the oxidative stress induced by administration of CCl4 the growth of arachidonic and docozahexaenoic acids in the neutral lipids fractions was observed if compare with the norm. At the same time, the presented fatty acids in the phospholipids fractions remained unchanged. At oxidative stress the phospholipids fraction reacts to levels of arachidonic and docozahexaenoic acids just only as a result of administrating phospholipids with omega-3 fatty acids. The most attractive is the change of correlation C20:4/C22:6--increasing at administration of CCl4 and decreasing both at phospolipids and vitamin E injection. Thus, at the oxidative stress the first reacting ones are the fatty acids of neutral lipids microsomal membranes.     

Regulation of intracellular lipid metabolism by the preparation of omega-3 phospholipids from marine organisms in deficiency of essential fatty acids in rats

It has been established that a deficit of essential fatty acids (EFA) in the animal organism induces specific modifications of composition of fatty acid (FA) of general phospholipids and plasmalogenic P1 in microsomal tissue membranes with various functions and affects the activity of phospholipase A2. It has been shown that arachidonic (AA), docosapentaenoic (DPA) and docosahexaenoic (DHA) acids in the composition of general phospholipids - phosphatidylcholine (PC), phosphatidylethanolamine (PEA) and plasmalogens PC and PEA react to EFA deficit in the organism. Quantitative redistribution of AA, DPA, DHA of FA in general phospholipids and plasmalogenic microsomal membranes depending on their functions was found under EFA deficit in the organism. Deficit of DHA and plasmalogenic phospholipids evidences that the status of cell plasmalogens affects the level of PUFA at EFA deficit in the organism. AA and DHA can be a selective target for plasmalogens. The drug of omega-3 phospholipids, considerable amount of DHA and eicosapentaenoic (EPA)FA being present in their structure, increases the amount of plasmalogens and decreases the amount of AA in the brain, heart and reproductive organs. It was also found that EFA deficit in the organism favours the increase of lisoPEA, lisoPC, free FA (FFA) connected with the increase of activity of endogenic phospholippase A2 and plasmalogen-selective phospholipase A2. The omega-3 phospholipase from marine organisms at EFA defecit decreases the amount of FFA, lisophospholipids and activity of phospholipase A2 in the microsomas of the studied tissues. The drug of omega-3 phospholipids normalizes the state and functions of the brain, liver, and heart tissues, reproductive organs against a background of EFA defecit and regulates the synthesis of biologocically active metabolites of AA in the organism.     

Impact of polyunsaturated fatty acids on cytoskeletal linkage of L-selectin

Polyunsaturated fatty acid [omega-3 polyunsaturated fatty acids (omega-3PUFAs)] incorporation into cell membranes has been shown to have potent anti-inflammatory activity, though the mechanisms involved are only partially characterized. Here, we show that PUFA enrichment of T cell membranes decreased the overall expression of L-selectin as well as a highly conserved epitope on L-selectin that may serve as a marker for optimal protein function. Additionally, PUFA enrichment inhibited L-selectin cytoskeletal association, which is thought to be important for optimal functional activity. In support of this, PUFA enrichment of gammadelta T cell membranes reduced L-selectin-dependent rolling interactions under conditions mimicking physiological flow. Taken together, these data suggest that the anti-inflammatory activity of omega-3 polyunsaturated fatty acids may be due, in part, to a novel effect on L-selectin, namely PUFA reduction or prevention of cytoskeletal association of L-selectin.     

Effect of phospholipids containing omega-3 fatty acids on structural changes of microsomal lipids in cell membranes of functionally different cells

As a result of the experimental researches conducted it has been shown that administration of some normal animal marine phospholipids (PL) including in their structure omega-3 polyunsaturated fatty acids (PUFA) provides for quantitative changes of individual PL, fatty acids (FA) content and quantity in general and individual PL of liver, heart, brain and gonads microsomes. While estimating general microsomal PL fraction FA content under the action of PL omega-3 PUFA FA concentration change, unsaturation index (omega 6/omega 3) and relation of arachidonic acid to docosahexenic (AA/DHA) decrease have been identified. The decrease of AA/DHA relationship occurs due to AA and DHA quantitative changes. In the case of AA increase in some tissues there is observed the decrease of docosapentaenic acid and increase of DHA and eucosapentaenic (EPA) acidds. As a result of studying FA content in the individual PL composition it has been identified that certain PL classes characteristic for some tissues respond by changes of some certain FA. The relationship omega 6/omega 3 has been shown as decreasing in phosphatidilcholine (PC) all tissues microsomes (liver, gonads, heart, brain), in phosphatidilethanolamine (PEA) of liver and cardiac microsomes, in phosphatidilserine (PS) this relationship relationship decreases in the liver, brain and heart, for phosphatidilinositole (PI) the changes take place in liver, gonads, brain. Simultaneously, the decrease of AA/DHA relationship in the individual PL decrease of AA and increase of EPA and DHA depend on the tested tissues. The marine phospholipids might be supposed to render their effect on AA metabolism resulting in AA/DHA relationship in PEA and PS relationship displays itself as specific and depends on the tissues functions. The preference of PEA and PS use by certain tissues microsomes could be explained by their membrane protective capability.     

Modification of membrane phospholipid fatty acyl composition in a leukemic T cell line: effects on receptor mediated intracellular Ca2+ increase.

The effect of modifying fatty acyl composition of cellular membrane phospholipids on receptor-mediated intracellular free Ca2+ concentration ([Ca2+]i) increase was investigated in a leukemic T cell line (JURKAT). After growing for 72 h in medium supplemented with unsaturated fatty acids (UFAs) and alpha-tocopherol, the fatty acyl composition of membrane phospholipids in JURKAT cells was extensively modified. Each respective fatty acid supplemented in the culture medium was readily incorporated into phosphatidylinositol, phosphatidylserine, phosphatidylethanolamine and phosphatidylcholine in the JURKAT cells. The total n-6 fatty acyl content was markedly reduced in phosphatidylinositol and phosphatidylcholine of cells grown in the presence of n-3 fatty acids (alpha-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid). Conversely, in the presence of n-6 fatty acids (linoleic acid and arachidonic acid), the total n-3 fatty acyl content was reduced in all the phospholipids examined. In n-3 and n-6 polyunsaturated fatty acid (PUFA) modified JURKAT cells, the total n-9 monounsaturated fatty acyl content in the phospholipids were markedly reduced. Changing the fatty acyl composition of membrane phospholipids in the JURKAT cells appears to have no affect on the presentation of the T cell receptor/CD3 complex or the binding of anti-CD3 antibodies (OKT3) to the CD3 complex. However, the peak increase in [Ca2+]i and the prolonged sustained phase elicited by OKT3 activation were suppressed in n-3 and n-6 PUFA but not in n-9 monounsaturated fatty acid modified cells. In Ca2+ free medium, OKT3-induced transient increase in [Ca2+]i representing Ca2+ release from the inositol 1,4,5-trisphosphate-sensitive Ca2+ stores, were similar in control and UFA modified cells. Using Mn2+ entry as an index of plasma membrane Ca2+ permeability, the rate of fura-2 fluorescence quenching as a result of Mn2+ influx stimulated by OKT3 in n-9 monounsaturated fatty acid modified cells was similar to control cells, but the rates in n-3 and n-6 PUFA modified cells were significantly lower. These results suggest that receptor-mediated Ca2+ influx in JURKAT cells is sensitive to changes in the fatty acyl composition of membrane phospholipids and monounsaturated fatty acids appears to be important for the maintenance of a functional Ca2+ influx mechanism.     

The ability of melatonin to counteract lipid peroxidation in biological membranes

This paper reviews recent data relevant to the antioxidant effects of melatonin with special emphasis on the changes produced in polyunsaturated fatty acids located in the phospholipids of biological membranes. The onset of lipid peroxidation within cellular membranes is associated with changes in their physicochemical properties and with the impairment of protein functions located in the membrane environment. All cellular membranes are especially vulnerable to oxidation due to their high concentration of polyunsaturated fatty acids. These processes combine to produce changes in the biophysical properties of membranes that can have profound effects on the activity of membrane-bound proteins. This review deals with aspects for lipid peroxidation of biological membranes in general, but with some emphasis on changes of polyunsaturated fatty acids, which arise most prominently in membranes and have been studied extensively in our laboratory. The article provides current information on the effect of melatonin on biological membranes, changes in fluidity, fatty acid composition and lipid-protein modifications during the lipid peroxidation process of photoreceptor membranes and modulation of gene expression by the hormone and its preventive effects on adriamycin-induced lipid peroxidation in rat liver. Simple model systems have often been employed to measure the activity of antioxidants. Although such studies are important and essential to understand the mechanisms and kinetics of antioxidant action, it should be noted that the results of simple in vitro model experiments cannot be directly extrapolated to in vivo systems. For example, the antioxidant capacity of melatonin, one of the important physiological lipophilic antioxidants, in solution of pure triglycerides enriched in omega-3 polyunsaturated fatty acids is considerably different from that in subcellular membranes.     

Antioxidant modulation of oxidant-stimulated uptake and release of arachidonic acid in eicosapentaenoic acid-supplemented human lymphoma U937 cells

Omega-3 polyunsaturated fatty acids (PUFA) are increasingly finding use as treatments for a variety of medical conditions. PUFA supplementation can, however, result in increased oxidative stress causing elevated turnover rate of membrane phospholipids, impairment of membrane integrity and increased formation of inflammatory mediators. The aim of this study was to determine which antioxidant compounds were most effective in ameliorating the stimulation of phospholipid turnover by oxidative stress. U937 cells were supplemented with eicosapentaenoic acid and either ascorbic acid, alpha-tocopherol, beta-carotene or astaxanthin prior to being challenged with oxidant. Although all antioxidants were found to be effective in decreasing oxidant-stimulated peroxide formation, only alpha-tocopherol significantly decreased oxidant-stimulated release of 3H-labeled arachidonic acid (AA), while ascorbic acid markedly increased release. All antioxidants except alpha-tocopherol decreased oxidant-stimulated 3H-AA uptake. Our data suggest that antioxidants are not equally effective in combating the effects of oxidative stress upon membrane phospholipid turnover, and that optimal protection will require mixtures of antioxidants.     

Influence of dietary fat on the lipid composition of rat brain synaptosomal and microsomal membranes.

The modulation of rat brain microsomal and synaptosomal membrane lipid by diet fat was examined. Brain synaptosomal and microsomal membrane composition was compared for rats fed on diets containing either soya-bean oil (SBO), SBO plus choline, SBO lecithin, sunflower oil (SFO), chow or low-erucic acid rape-seed oil (LER) for 24 days. Cholesterol and phosphatidylcholine levels in both membranes were altered by diet. Diet fat also affected the microsomal content of sphingomyelin. Change in membrane phosphatidylcholine level was related to the relative balance of omega-6, omega-3 and monounsaturated fatty acids within the diets fed. The highest phosphatidylcholine levels appeared in membranes of animals fed on SBO lecithin and the lowest in those fed on LER. Microsomal membrane cholesterol and sphingomyelin content increased by feeding on SBO lecithin. In both synaptosomal and microsomal membranes a highly significant correlation was observed between membrane phosphatidylcholine and cholesterol content. The fatty acyl composition of phospholipids from both membranes also altered with diet and age. Alteration in fatty acid composition was observed in response to dietary levels of omega-6, omega-3 and monounsaturated fatty acids, but the unsaturation index of each phospholipid remained constant for all diet treatments. These changes in lipid composition suggest that dietary fat may be a significant modulator in vivo of the physicobiochemical properties of brain synaptosomal and microsomal membranes.     

Modulation of enzymatic activities by n-3 polyunsaturated fatty acids to support cardiovascular health

Epidemiological evidence from Greenland Eskimos and Japanese fishing villages suggests that eating fish oil and marine animals can prevent coronary heart disease. Dietary studies from various laboratories have similarly indicated that regular fish oil intake affects several humoral and cellular factors involved in atherogenesis and may prevent atherosclerosis, arrhythmia, thrombosis, cardiac hypertrophy and sudden cardiac death. The beneficial effects of fish oil are attributed to their n-3 polyunsaturated fatty acid (PUFA; also known as omega-3 fatty acids) content, particularly eicosapentaenoic acid (EPA; 20:5, n-3) and docosahexaenoic acid (DHA; 22:6, n-3). Dietary supplementation of DHA and EPA influences the fatty acid composition of plasma phospholipids that, in turn, may affect cardiac cell functions in vivo. Recent studies have demonstrated that long-chain omega-3 fatty acids may exert beneficial effects by affecting a wide variety of cellular signaling mechanisms. Pathways involved in calcium homeostasis in the heart may be of particular importance. L-type calcium channels, the Na+-Ca2+ exchanger and mobilization of calcium from intracellular stores are the most obvious key signaling pathways affecting the cardiovascular system; however, recent studies now suggest that other signaling pathways involving activation of phospholipases, synthesis of eicosanoids, regulation of receptor-associated enzymes and protein kinases also play very important roles in mediating n-3 PUFA effects on cardiovascular health. This review is therefore focused on the molecular targets and signaling pathways that are regulated by n-3 PUFAs in relation to their cardioprotective effects.     

Lipid peroxidation and disturbance in Ca2+ transport through sarcoplasmic reticulum membranes during E-avitaminosis]

The antioxidant effect of alpha-tocopherol in biolgoical membranes in vivo is described. Experimental E-avitaminosis is accompanied by accumulation of products of free-radical oxidation of phospholipids and by a loss of Ca2+-transporting ability of the muscle cells microsomal fraction. The role of alpha-tocopherol in stabilization and as a "radical trap" in biological membranes is discussed.     

Nature of the modifying action of polyunsaturated fatty acids on the growth of transplantable tumors of different types

Modification effect of sodium salts and ethers of linolenic, arachidonic and alpha-linolenic acids on the growth of transplantable mouse tumors was examined. Polyunsaturated fatty acids (PUFA) enhanced the growth of mammary adenocarcinoma Ca-755, whereas the opposite effect was observed in mice with leukemia L-1210 and sarcoma 180. No differences in the growth of melanoma B-16 and Lewis lung carcinoma were noted in control and experimental animals. Modification effect of PUFA was significantly suppressed by prostaglandin inhibitor indomethacin and to a lesser extent by antioxidant alpha-tocopherol.     

Intermembrane transfer and antioxidant action of alpha-tocopherol in liposomes

Intermembrane transfer and exchange of tocopherol are not well understood. To study this we tested the ability of alpha-tocopherol containing unilamellar donor liposomes to inhibit the accumulation of lipid peroxidation products in acceptor liposomes. With molar ratios of alpha-tocopherol:phospholipids from 1:100 to 1:1000 in donor liposomes prepared by sonication of lipid dispersions, alpha-tocopherol was incorporated into both monolayers and was homogenously distributed in monomeric form without forming clusters in the liposomes. Concentrations of alpha-tocopherol which completely prevented the peroxidation of lipids were chosen for donor liposomes. Hence inhibition of lipid peroxidation in mixtures of donor and acceptor liposomes was determined by the antioxidant effect of alpha-tocopherol in acceptor liposomes which resulted from intermembrane transfer and exchange of alpha-tocopherol. Evidence was obtained that this was not due to fusion of donor with acceptor liposomes. The efficiency of the "intermembrane" antioxidant action of tocopherol was more pronounced when donor liposomes contained unsaturated phospholipids, indicating that the presence of unsaturated fatty acids in the outer monolayer phospholipids facilitates intermembrane tocopherol exchange.     

Omega-3 polyunsaturated fatty acids improve host response in chronic Pseudomonas aeruginosa lung infection in mice

Pseudomonas aeruginosa is a gram-negative bacilli frequently encountered in human pathology. This pathogen is involved in a large number of nosocomial infections and chronic diseases. Herein we investigated the effects of polyunsaturated fatty acids (PUFA) in chronic Pseudomonas aeruginosa lung infection. C57BL/6 mice were fed for 5 wk with specifically designed diets with high contents in either omega-3 (omega-3) or omega-6 PUFA and compared to a control diet. P. aeruginosa included in agarose beads was then instilled intratracheally, and the animals were studied for 7 days. On the 4th day, the mice fed with the omega-3 diet had a higher lean body mass gain and a lower omega-6:omega-3 ratio of fatty acids extracted from the lung tissue compared with the other groups (P < 0.05). The omega-3 group had the lowest mortality. Distal alveolar fluid clearance (DAFC) as well as the inflammatory response and the cellular recruitment were higher in the omega-3 group on the 4th day. The effect on DAFC was independent of alpha-epithelial Na(+) channels (alpha-ENaC), beta-ENaC, and alpha(1)-Na-K-ATPase mRNA expressions, which were not altered by the different diets. In conclusion, a diet enriched in omega-3 PUFA can change lung membrane composition and improve survival in chronic pneumonia. This effect on survival is probably multifactorial involving the increased DAFC capacity as well as the optimization of the initial inflammatory response. This work suggests that a better control of the omega-6/omega-3 PUFA balance may represent an interesting target in the prevention and/or control of P. aeruginosa infection in patients.     

Fatty acid-related modulations of membrane fluidity in cells: detection and implications

Abstract

Metabolic homeostasis of fatty acids is complex and well-regulated in all organisms. The biosynthesis of saturated fatty acids (SFA) in mammals provides substrates for β-oxidation and ATP production. Monounsaturated fatty acids (MUFA) are products of desaturases that introduce a methylene group in cis geometry in SFA. Polyunsaturated fatty acids (n-6 and n-3 PUFA) are products of elongation and desaturation of the essential linoleic acid and α-linolenic acid, respectively. The liver processes dietary fatty acids and exports them in lipoproteins for distribution and storage in peripheral tissues. The three types of fatty acids are integrated in membrane phospholipids and determine their biophysical properties and functions. This study was aimed at investigating effects of fatty acids on membrane biophysical properties under varying nutritional and pathological conditions, by integrating lipidomic analysis of membrane phospholipids with functional two-photon microscopy (fTPM) of cellular membranes. This approach was applied to two case studies: first, pancreatic beta-cells, to investigate hormetic and detrimental effects of lipids. Second, red blood cells extracted from a genetic mouse model defective in lipoproteins, to understand the role of lipids in hepatic diseases and metabolic syndrome and their effect on circulating cells.     

The effect of N-stearoylethanolamine on lipid composition of the metastases and conditionally normal lung tissue in mice with Lewis carcinoma

Influence of NSE on lipid composition of metastases and the neighbouring conditionally normal lung tissue in mice with Lewis carcinoma was investigated. The processes of peroxidation in investigated tissues were also studied. It was shown that under the influence of NSE the high level of antioxidant activity in the metastases was decreased, while in the neighbouring conditionally normal lung tissue the catalase activity was increased. The content of the thiobarbituric acid-reactive substances in comparison with animals which were not fed by NSE was decreased. The development of carcinoma was accompanied by significant decrease of cholesterol level and by the increase of unsaturated fatty acids esterified in membrane phospholipids in both the metastases and the neighbouring conditionally normal lung tissue. An analysis of the phospholipid spectra shows that under tumor growth in investigated tissues the high-level lysophosphatidylcholine (LPC) was observed. The content of phosphatidyl choline (PC), phosphatidyl ethanolamine (PE), phosphatidyl serine (PS) was found to be significantly lower than in the lung of intact animals. It was found that administration of NSE to tumor-bearing mice contributed to the increase of cholesterol level, to the decrease of omega-6/omega-3 ratio polyunsaturated fatty acids of total phospholipids. NSE modulated the phospholipid membrane composition in both the metastases and the neighbouring conditionally normal lung tissue.     

An antioxidant-like action for non-peroxidisable phospholipids using ferrous iron as a peroxidation initiator

The degradation of phospholipids containing polyunsaturated fatty acids, termed peroxidation, poses a constant challenge to membranes lipid composition and function. Phospholipids with saturated (e.g. PC 16:0/16:0) and monounsaturated fatty acids (e.g. PC 16:0/18:1) are some of the most common phospholipids found in membranes and are generally not peroxidisable. The present experiments show that these non-peroxidisable phospholipids, when present in liposomes with peroxidisable phospholipids (i.e. those containing polyunsaturated fatty acids) such as PC 16:0/18:2 and Soy PC, produce an inhibitory effect on rates of peroxidation induced by ferrous-iron. This inhibitory effect acts to extend the duration of the lag phase by several-fold. If present in natural systems, this action could enhance the capacity of conventional antioxidant mechanisms in membranes. The results of this preliminary work suggest that non-peroxidisable phospholipids may exert an antioxidant-like action in membranes.     

Phospholipids and their fatty acids in mitochondria, synaptosomes and myelin from the liver and brain of trout and rat: a new view on the role of fatty acids in membranes

The content of different phospholipids (PL) and their fatty acid (FA) composition in subcellular fractions from the liver and brain of rat (Rattus rattus) and trout (Salmo irideus) were estimated. It was shown that despite higher content of unsaturated fatty acids in myelin compared to synaptosomes, the unsaturation index of the latter is equal or higher than that of myelin. The total content of PL polyunsaturated fatty acids (PUFA) was shown to be higher in membrane structures with more active ion transport (mitochondria). This feature seemed to be characteristic of membranes from both representatives of homoiotherms and poikilotherms studied. A possible role for PUFA information within the lipid monolayer of areas with different capacity to accept electrons and transport them along a sort of intermolecular 'tunnel' is discussed. The double bonds of PUFA in this area seem to be able to produce bonds similar to conjugated bonds.     

Increased plasma levels of palmitoleic acid may contribute to beneficial effects of Krill oil on glucose homeostasis in dietary obese mice

Omega-3 polyunsatuarted fatty acids (PUFA) are associated with hypolipidemic and anti-inflammatory effects. However, omega-3 PUFA, usually administered as triacylglycerols or ethyl esters, could also compromise glucose metabolism, especially in obese type 2 diabetics. Phospholipids represent an alternative source of omega-3 PUFA, but their impact on glucose homeostasis is poorly explored. Male C57BL/6N mice were fed for 8 weeks a corn oil-based high-fat diet (cHF) alone or cHF-based diets containing eicosapentaenoic acid and docosahexaenoic acid (~3%; wt/wt), admixed either as a concentrate of re-esterified triacylglycerols (ω3TG) or Krill oil containing mainly phospholipids (ω3PL). Lean controls were fed a low-fat diet. Insulin sensitivity (hyperinsulinemic-euglycemic clamps), parameters of glucose homeostasis, adipose tissue function, and plasma levels of N-acylethanolamines, monoacylglycerols and fatty acids were determined.Feeding cHF induced obesity and worsened (~4.3-fold) insulin sensitivity as determined by clamp. Insulin sensitivity was almost preserved in ω3PL but not ω3TG mice. Compared with cHF mice, endogenous glucose production was reduced to 47%, whereas whole-body and muscle glycogen synthesis increased ~3-fold in ω3PL mice that showed improved adipose tissue function and elevated plasma adiponectin levels. Besides eicosapentaenoic and docosapentaenoic acids, principal component analysis of plasma fatty acids identified palmitoleic acid (C16:1n-7) as the most discriminating analyte whose levels were increased in ω3PL mice and correlated negatively with the degree of cHF-induced glucose intolerance.While palmitoleic acid from Krill oil may help improve glucose homeostasis, our findings provide a general rationale for using omega-3 PUFA-containing phospholipids as nutritional supplements with potent insulin-sensitizing effects.     

Corticosteroid effect on Caco-2 cell lipids depends on cell differentiation

Previous studies from our laboratory have indicated that secondary hyperaldosteronism affects phospholipids of rat colonic enterocytes. To assess whether this represents a direct effect of mineralocorticoids on enterocytes, the role of aldosterone and dexamethasone in the regulation of lipid metabolism was examined in Caco-2 cells during development of their enterocyte phenotype. Differentiation of Caco-2 cells was associated with increased levels of triglycerides (TG) and cholesteryl esters (CE), a decreased content of cholesterol and phospholipids and changes in individual phospholipid classes. The phospholipids of differentiated cells had a higher content of n-6 polyunsaturated fatty acids (PUFA) and lower amounts of monounsaturated (MUFA) and saturated fatty acids than subconfluent undifferentiated cells. Differentiated cells exhibited a higher ability to incorporate [3H]arachidonic acid (AA) into cellular phospholipids and a lower ability for incorporation into TG and CE. Incubation of subconfluent undifferentiated cells with aldosterone or dexamethasone was without effect on the content of lipids, their fatty acids and [3H]AA incorporation. In contrast, aldosterone treatment of differentiated cells diminished the content of TG, increased the content of phospholipids and modulated their fatty acid composition. The percentage of n-6 and n-3 PUFA in phospholipids was increased and that of MUFA decreased, whereas no changes in TG were observed. The incorporation of [3H]AA into phospholipids was increased and into TG decreased and these changes were blocked by spironolactone. Treatment of differentiated cells with dexamethasone increased their CE content but no effect was identified upon other lipids, their fatty acid composition and on the incorporation of [3H]AA. As expected for the involvement of corticosteroid hormones the mineralocorticoid and glucocorticoid receptors were identified in Caco-2 cells by RT-PCR. The results suggest that aldosterone had a profound influence on lipid metabolism in enterocytes and that its effect depends on the stage of differentiation. The aldosterone-dependent changes occurring in phospholipids and their fatty acid composition may reflect a physiologically important phenomenon with long-term consequences for membrane structure and function.