Acid Composition Of Membrane Phospholipids Research Articles

Deficiency of (n-6) but Not (n-3) Polyunsaturated Fatty Acids Inhibits the Secretagogue Effect of Prolactin in Lactating Rat Mammary Epithelial Cells

The repercussions of various kinds of dietary polyunsaturated fatty acid (PUFA) deficiencies on the fatty acid composition of membranes and on the secretory activity of lactating female rat mammary epithelial cells were investigated. Primiparous female rats were fed different PUFA diets from weaning: adequate (n-6) and (n-3) PUFA supply; overall PUFA deficiency; specific (n-6) PUFA deficiency or specific (n-3) PUFA deficiency. Mammary gland phospholipids contained very low amount of (n-3) PUFA in control rats, and only 1% docosahexaenoic acid. The fatty acid composition of membrane phospholipids reflected the type of diet received by the animals, i.e., the diets deficient in the (n-3) or (n-6) PUFA series resulted in lower (n-3) or (n-6) PUFA, and the (n-3) + (n-6) deficient diet caused a true overall PUFA deficiency in the membranes. The morphology of cells from overall PUFA- or (n-6) PUFA-deficient rats showed an accumulation of secretory vesicles in the cytoplasm. Basal casein secretion was independent of the diet and of the composition of membrane phospholipids. However, prolactin did not have a secretagogue effect on cells from (n-6) PUFA- or overall PUFA-deficient rats but retained this effect on cells from (n-3)-deficient rats. These results emphasize the specific role of (n-6) PUFA in the functioning of the lactating mammary epithelial cell.

Dietary intake of n-3 polyunsaturated fatty acids alters the lipid mediator profile of the kidney but does not attenuate renal insufficiency

The efficacy of n-3 polyunsaturated fatty acids (PUFAs) in improving outcomes in a renal ischemia-reperfusion injury (IRI) model has previously been reported. However, the underlying mechanisms remain poorly understood and few reports demonstrate how dietary n-3 PUFAs influence the composition of membrane phospholipids in the kidney. Additionally, it has not been elucidated whether perilla oil (PO), which is mainly composed of the n-3 alpha-linolenic acid, mitigates renal IRI. In this study, we investigated the effect of dietary n-3 PUFAs (PO), compared with an n-6 PUFA-rich soybean oil (SO) diet, on IRI-induced renal insufficiency in a rat model. Levels of membrane phospholipids containing n-3 PUFAs were higher in the kidney of PO-rich diet-fed rats than the SO-rich diet-fed rats. Levels of blood urea nitrogen and serum creatinine were significantly higher in the ischemia-reperfusion group than the sham group under both dietary conditions. However, no significant differences were observed in blood urea nitrogen, serum creatinine, or histological damage between PO-rich diet-fed rats and SO-rich diet-fed rats. In the kidney of PO-rich diet-fed rats, levels of arachidonic acid and arachidonic acid-derived pro-inflammatory lipid mediators were lower than SO-rich diet-fed rats. Eicosapentaenoic acid and eicosapentaenoic acid-derived lipid mediators were significantly higher in the kidney of PO-rich than SO-rich diet-fed rats. These results suggest that dietary n-3 PUFAs alter the fatty acid composition of membrane phospholipids and lipid mediators in the kidney; however, this does not attenuate renal insufficiency or histological damage in a renal IRI model.

Acyl-CoA synthetase 6 regulates long-chain polyunsaturated fatty acid composition of membrane phospholipids in spermatids and supports normal spermatogenic processes in mice.

Long-chain polyunsaturated fatty acids (LCPUFAs), such as docosahexaenoic acid (DHA, 22:6) and docosapentaenoic acid (DPA, 22:5), have versatile physiologic functions. Studies have suggested that DHA and DPA are beneficial for maintaining sperm quality. However, their mechanisms of action are still unclear because of the poor understanding of DHA/DPA metabolism in the testis. DHA and DPA are mainly stored as LCPUFA-containing phospholipids and support normal spermatogenesis. Long-chain acyl-conenzyme A (CoA) synthetase (ACSL) 6 is an enzyme that preferentially converts LCPUFA into LCPUFA-CoA. Here, we report that ACSL6 knockout (KO) mice display severe male infertility due to attenuated sperm numbers and function. ACSL6 is highly expressed in differentiating spermatids, and ACSL6 KO mice have reduced LCPUFA-containing phospholipids in their spermatids. Delayed sperm release and apoptosis of differentiated spermatids were observed in these mice. The results of this study indicate that ACSL6 contributes to the local accumulation of DHA- and DPA-containing phospholipids in spermatids to support normal spermatogenesis.—Shishikura, K., Kuroha, S., Matsueda, S., Iseki, H., Matsui, T., Inoue, A., Arita, M. Acyl-CoA synthetase 6 regulates long-chain polyunsaturated fatty acid composition of membrane phospholipids in spermatids and supports normal spermatogenic processes in mice.

Sirt1 counteracts decrease in membrane phospholipid unsaturation and diastolic dysfunction during saturated fatty acid overload

BackgroundThe fatty acid (FA) composition of membrane phospholipid reflects at least in part dietary fat composition. Saturated FA (SFA) suppress Sirt1 activity, while monounsaturated FA (MUFA) counteract this effect. ObjectiveWe explored a role of Sirt1 in homeostatic control of the fatty acid composition of membrane phospholipid in the presence of SFA overload. Methods and resultsSirt1 deficiency in cardiomyocytes decreased the expression levels of liver X receptor (LXR)-target genes, particularly stearoyl-CoA desaturase-1 (Scd1), a rate-limiting enzyme in the cellular synthesis of MUFA from SFA, increased membrane SFA/MUFA ratio, and worsened left ventricular (LV) diastolic function in mice fed an SFA-rich high fat diet. In cultured cardiomyocytes, Sirt1 knockdown (KD) exacerbated the palmitate overload-induced increase in membrane SFA/MUFA ratio, which was associated with decrease in the expression of LXR-target genes, including Scd1. Forced overexpression of Scd1 in palmitate-overloaded Sirt1KD cardiomyocytes lowered the SFA/MUFA ratio. Nicotinamide mononucleotide (NMN) increased Sirt1 activity and Scd1 expression, thereby lowering membrane SFA/MUFA ratio in palmitate-overloaded cardiomyocytes. These effects of NMN were not observed for Scd1KD cardiomyocytes. LXRα/βKD exacerbated palmitate overload-induced increase in membrane SFA/MUFA ratio, while LXR agonist T0901317 alleviated it. NMN failed to rescue Scd1 protein expression and membrane SFA/MUFA ratio in palmitate-overloaded LXRα/βKD cardiomyocytes. The administration of NMN or T0901317 showed a dramatic reversal in membrane SFA/MUFA ratio and LV diastolic function in SFA-rich HFD-fed mice. ConclusionCardiac Sirt1 counteracted SFA overload-induced decrease in membrane phospholipid unsaturation and diastolic dysfunction via regulating LXR-mediated transcription of the Scd1 gene.

Characterization of Bacterial Membrane Fatty Acid Profiles for Biofilm Cells.

When exposed to environmental stresses, bacteria can modulate its fatty acid composition of membrane phospholipids in order to optimize membrane fluidity. Characterization of bacterial membrane fatty acid profiles is thus an interesting indicator of cellular physiological state. The methodology described here aims to improve the recovering of biofilm cells for the characterization of their fatty acid profiles. The saponification reagent is directly applied on the whole biofilm before the removal of cells from the inert surface. In this way, maximum of the cells and their fatty acids can be recovered from the deepest layers of the biofilm.

The role of defensin fragment in the regulation of fatty acid composition of membrane phospholipids in epithelial-like cells

It is shown that a tetrapeptide fragment of defensin does not alter the phospholipid composition in the membranes of CHO-K1 cells but regulates the fatty acid composition of phosphatidylcholine, phosphatidylethanolamine (PEA), phosphatidylserine (PS), and phosphatidylinositol (PI). Incubation of the cells in the presence of this tetrapeptide resulted in modification of unsaturated fatty acid composition in the studied phospholipids. The content of monoenoic (mainly C18 : 1ω9) and/or dienoic (C18 : 2ω6) fatty acids increased, while the level of polyenoic fatty acids decreased. It was found that in the polyenoic fatty acid group of the PEA, PS and PI molecules, the ω3-/ω6-acid ratio decreased mainly due to the lower content of long-chain ω3-acids with 20 and/or 22 carbonic atoms. The possible role of this peptide in inhibition of the activity of Δ6- and Δ5-desaturases involved in the synthesis of long-chain polyenoic fatty acids, the quantitative alteration of which in phospholipids influences physicochemical parameters in cell membranes, is discussed.

Do fatty acids affect fetal programming?

BackgroundIn this study discussed the primary and regulatory roles of fatty acids, and investigated the affects of fatty acids on metabolic programming.MethodsReview of the literature was carried out on three electronic databases to assess the roles of fatty acids in metabolic programming. All abstracts and full-text articles were examined, and the most relevant articles were selected for screening and inclusion in this review.ResultsThe mother’s nutritional environment during fetal period has important effects on long term health. Fatty acids play a primary role in growth and development. Alterations in fatty acid intake in the fetal period may increase the risk of obesity and metabolic disorders in later life. Maternal fatty acid intakes during pregnancy and lactation are passed to the fetus and the newborn via the placenta and breast milk, respectively. Imbalances in fatty acid intake during the fetal period change the fatty acid composition of membrane phospholipids, which can cause structural and functional problems in cells. Additionally, the metabolic and neuroendocrine environments of the fetus and the newborn play key roles in the regulation of energy balance.ConclusionsImbalances in fatty acid intake during pregnancy and lactation may result in permanent changes in appetite control, neuroendocrine function and energy metabolism in the fetus, leading to metabolic programming. Further studies are needed to determine the role of fatty acid intake in metabolic programming.

Effect of voluntary running on fatty acid composition in membrane phospholipids and amount of lipotoxic intermediates in hereditary hypertriglyceridemic rats

Objectives: Lipid deposition in the extraadipose tissue, mostly in the liver and muscle is one of the most serious factor associated with obesity and metabolic syndrome (MS). More important than total amount of tissue lipids is their composition, mostly the properties of fatty acids and quantity of lipotoxic intermediates (ceramides and diacylglyceroles). The positive role of physical activity on the obesity-related disorders is well documented but its effect on membrane fatty acid composition and concentration of lipotoxic intermediates is unclear.

Fat-1 gene modulates the fatty acid composition of femoral and vertebral phospholipids

Dietary polyunsaturated fatty acid (PUFA) incorporation into bone may alter its metabolism through changes in the fatty acid composition of membrane phospholipids. Alteration of the membrane phospholipid fatty acid composition may influence bone cell signalling and, potentially, bone mineralization. The objective of this study was to use the fat-1 mouse, a transgenic model that synthesizes n-3 from n-6 PUFA, to determine if the fat-1 gene modulates the fatty acid composition of femoral and vertebral phospholipids, and if so, whether the fatty acid levels would correlate with bone mineral density (BMD) at both skeletal sites. Male and female wild-type and fat-1 mice were fed an AIN93-G diet, containing 10% safflower oil, from weaning to 12 weeks of age. The fatty acid composition of femoral and vertebral phospholipids was measured by gas liquid chromatography. At 12 weeks of age, phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine fractions in the vertebrae of fat-1 mice had a significantly lower n-6/n-3 ratio than wild-type mice (p<0.05). In fat-1 femurs, these fractions, along with phosphatidylinositol, had a lower n-6/n-3 ratio than wild-type mice (p<0.001). Docosahexaenoic acid (DHA) was positively correlated with BMD in all fractions in the vertebrae, and in phosphatidylinositol and phosphatidylserine in the femur (p<0.05). Overall, the fat-1 gene resulted in changes in the fatty acid composition of both femoral and vertebral phospholipids. Significant correlations between DHA and BMD may indicate a positive effect on bone mineralization.

Lipomobilization in periparturient dairy cows influences the composition of plasma nonesterified fatty acids and leukocyte phospholipid fatty acids

The periparturient period is characterized by sudden changes in metabolic and immune cell functions that predispose dairy cows to increased incidence of disease. Metabolic changes include alterations in the energy balance that lead to increased lipomobilization with consequent elevation of plasma nonesterified fatty acids (NEFA) concentrations. The objective of this study was to establish the influence of lipomobilization on fatty acid profiles within plasma lipid fractions and leukocyte phospholipid composition. Blood samples from 10 dairy cows were collected at 14 and 7 d before due date, at calving, and at 7, 14, and 30 d after calving. Total lipids and lipid fractions were extracted from plasma and peripheral blood mononuclear cells. The degree of lipomobilization was characterized by measurement of plasma NEFA concentrations. The fatty acid profile of plasma NEFA, plasma phospholipids, and leukocyte phospholipids differed from the composition of total lipids in plasma, where linoleic acid was the most common fatty acid. Around parturition and during early lactation, the proportion of palmitic acid significantly increased in the plasma NEFA and phospholipid fractions with a concomitant increase in the phospholipid fatty acid profile of leukocytes. In contrast, the phospholipid fraction of long-chain polyunsaturated fatty acids in leukocytes was diminished during the periparturient period, especially during the first 2 wk following parturition. This study showed that the composition of total plasma lipids does not necessarily reflect the NEFA and phospholipid fractions in periparturient dairy cows. These findings are significant because it is the plasma phospholipid fraction that contributes to fatty acid composition of membrane phospholipids. Increased availability of certain saturated fatty acids in the NEFA phospholipid fractions may contribute to altered leukocyte functions during the periparturient period.

N-3 long-chain fatty acids and regulation of glucose transport in two models of rat brain endothelial cells

Several in vivo studies suggest that docosahexaenoic acid (22:6 n-3), the main n-3 long-chain polyunsaturated fatty acids (LC-PUFA) of brain membranes, could be an important regulator of brain energy metabolism by affecting glucose utilization and the density of the two isoforms of the glucose transporter-1 (GLUT1) (endothelial and astrocytic). This study was conducted to test the hypothesis that 22:6 n-3 in membranes may modulate glucose metabolism in brain endothelial cells. It compared the impact of 22:6 n-3 and the other two main LC-PUFA, arachidonic acid (20:4 n-6) and eicosapentaenoic acid (20:5 n-3), on fatty acid composition of membrane phospholipids, glucose uptake and expression of 55-kDa GLUT1 isoform in two models of rat brain endothelial cells (RBEC), in primary culture and in the immortalized rat brain endothelial cell line RBE4. Without PUFA supplementation, both types of cerebral endothelial cells were depleted in 22:6 n-3, RBE4 being also particularly low in 20:4 n-6. After exposure to supplemental 20:4 n-6, 20:5 n-3 or 22:6 n-3 (15 μM, i.e. a physiological dose), RBEC and RBE4 avidly incorporated these PUFA into their membrane phospholipids thereby resembling physiological conditions, i.e. the PUFA content of rat cerebral microvessels. However, RBE4 were unable to incorporate physiological level of 20:4 n-6. Basal glucose transport in RBEC (rate of [ 3H]-3-o-methylglucose uptake) was increased after 20:5 n-3 or 22:6 n-3 supplementation by 50% and 35%, respectively, whereas it was unchanged with 20:4 n-6. This increase of glucose transport was associated with an increased GLUT1 protein, while GLUT1 mRNA was not affected. The different PUFA did not impact on glucose uptake in RBE4. Due to alterations in n-6 PUFA metabolism and weak expression of GLUT1, RBE4 seems to be less adequate than RBEC to study PUFA metabolism and glucose transport in brain endothelial cells. Physiological doses of n-3 LC-PUFA have a direct and positive effect on glucose transport and GLUT1 density in RBEC that could partly explain decreased brain glucose utilization in n-3 PUFA-deprived rats.

Gender differences in the PUFA-fatty acid composition of membrane phospholipids in rats

Gender differences in the PUFA-fatty acid composition of membrane phospholipids in rats

Role of collagen tripeptide fragment GER on activation of adhesion and modification of fatty acid composition in membrane phospholipids of CHO-K1 cells

It has been found that the multiply repeated tripeptide fragment GER (Gly-Glu-Arg) from different collagen types stimulates the nonspecific adhesion of CHO-K1 cells. Activation of cell adhesion is accompanied by modifications to the fatty acid composition in the phospholipids of the cell membrane. Cell incubation with the synthetic GER peptide increases the unsaturation index of phosphatidylcholin (PC), phosphatidylethanolamine (PEA), and phosphatidylinositol (PI). Arachidonic (C20:4ω6) acid is mainly contributed to the increased index of PI. Not only arachidonic acid but other unsaturated fatty acids, such as docosatetraenoic (C22:4ω6), docosapentaenoic (C22:5ω3), and docosahexaenoic (C22:6ω3), are responsible for the increased index of PC and PEA. In addition, the elevation of the relative content of polyenoic fatty acids in PI is concomitant with a reduced amount of monoenoic fatty acids, mainly due to decline in the oleic (C18:1) acid level. The role of GER peptide in (1) the activation of cell adhesion as a regulator of active or inactive states of integrin receptors; (2) modification of fatty acid composition in major classes of phospholipids as a modulator of the fluidity in annular lipid zones surrounding to the adhesive molecules is discussed.

Identification and Functional Expression of a Δ9‐Fatty Acid Desaturase from Psychrobacter urativorans in Escherichia coli

The Delta9-fatty acid desaturase is a key enzyme in the synthesis of unsaturated fatty acids. The fatty acid composition of membrane phospholipids in Psychrobacter urativorans is characterized by a high degree of desaturation at Delta9 position. Based on CODEHOP-mediated PCR strategy, a novel gene designated as PuFAD9, putatively encoding a Delta9-fatty acid desaturase (PuFAD9), was isolated from P. urativorans. The gene consists of 1,455 bp and codes for 484 amino acids. Analysis of the amino acid sequence reveals three histidine clusters and a hydropathy profile, typical for membrane-bound desaturases. Activity of the PuFAD9 protein, recombinantly expressed in Escherichia coli was confirmed by GC-MS analysis of the cellular fatty acid composition. It was found that the ratio between palmitoleic and palmitic acid in E. coli cells heterologously expressing the PuFAD9 gene was significantly affected by IPTG induction and the growth temperature.

Diet (n-3) Polyunsaturated Fatty Acid Content and Parity Affect Liver and Erythrocyte Phospholipid Fatty Acid Composition in Female Rats 3

The fatty acid composition of membrane phospholipids affects the physicochemical properties of the membrane and thus influences cell function. In this study, the effects of 1–4 sequential pregnancies on the phospholipid fatty acid compositions of the maternal liver and erythrocytes were determined in female rats fed diets containing α-linolenic acid (ALA), ALA and preformed docosahexaenoic acid (DHA; ALA+DHA), or minimal ALA (low ALA). Virgin females, fed the diets for commensurate durations, served as a control for reproduction. Liver and erythrocyte total phospholipid compositions were determined at weaning by TLC/GC. In both tissues, significant main effects of diet and reproductive status were detected for many fatty acids, but a significant interaction of diet, reproductive status, and duration of treatment (no. of reproductive cycles or equivalent time period for virgins) was detected only for DHA, 22:6(n-3). Primiparous dams fed the ALA and low ALA diet had decreased liver DHA content of 31% and 74%, respectively, compared with virgin females fed the ALA diet. Liver DHA did not decrease further after additional reproductive cycles. Liver DHA content was unchanged in parous dams fed the ALA+DHA diet, but virgin females fed this diet exhibited a 50% increase in liver DHA after 13 wk of treatment. Changes in erythrocyte DHA were of similar magnitude and time course to those observed in liver, suggesting that this tissue may serve as a marker for liver DHA status.

Fatty acids and early human development

Fatty acids play central roles in growth and development through their roles in membrane lipids, as ligands for receptors and transcription factors that regulate gene expression, precursor for eicosanoids, in cellular communication, and through direct interactions with proteins. Adverse fatty acid supplies during fetal and child development alter the fatty acid composition of membrane phospholipids and storage triglycerides with the potential to disrupt cellular environments, and program structure and function. Maternal fatty acid nutrition during pregnancy and lactation determines the transfer of essential n-6 and n-3, and non-essential trans fatty acids via the placenta and through human milk. Poor maternal docosahexaenoic acid (DHA) status increases risk of inadequate DHA to support brain and retinal development, delaying or limiting neural and visual system development. The implications of recent changes in the dietary fatty acids on maternal to infant fatty acid transfer, including the composition of human milk has been insufficiently studied.

The role of dietary fat in adipose tissue metabolism

Energy intake and expenditure tend on average to remain adjusted to each other in order to maintain a stable body weight, which is only likely to be sustained if the fuel mix oxidised is equivalent to the nutrient content of the diet. Whereas protein and carbohydrate degradation and oxidation are closely adjusted to their intakes, fat balance regulation is less precise and that fat is more likely to be stored than oxidised. It has been demonstrated that dietary fatty acids have an influence not only on the fatty acid composition of membrane phospholipids, thus modulating several metabolic processes that take place in the adipocyte, but also on the composition and the quantity of different fatty acids in adipose tissue. Moreover, dietary fatty acids also modulate eicosanoid presence, which have hormone-like activities in lipid metabolism regulation in adipose tissue. Until recently, the adipocyte has been considered to be no more than a passive tissue for storage of excess energy. However, there is now compelling evidence that adipocytes have a role as endocrine secretory cells. Some of the adipokines produced by adipose tissue, such as leptin and adiponectin, act on adipose tissue in an autocrine/paracrine manner to regulate adipocyte metabolism. Furthermore, dietary fatty acids may influence the expression of adipokines. The nutrients are among the most influential of the environmental factors that determine the way adipose tissue genes are expressed by functioning as regulators of gene transcription. Therefore, not only dietary fat amount but also dietary fat composition influence adipose tissue metabolism.

Omega-3 fatty acids and brain energy metabolism: Impact on the expression of glucose transporters and glucose transport activity in endothelial cells in culture

Alterations in cognitive performance and neuronal activity in animals defi cient in n-3 polyunsaturated fatty acids (PUFA) have been linked to the decrease in docosahexaenoic acid (22:6n-3, DHA) level in brain membranes. These alterations could partly result from changes in brain energy metabolism and namely in glucose transport activity. Indeed, we reported that several brain areas of rats raised on a diet defi cient in n-3 PUFAs have below-normal rates of glucose utilization [1]. We postulated that the quantity of glucose transporter GLUT1 in defi cient rats was functionally abnormal as its immunoreactivity was low. We present experimental data that evaluated: 1) the in vivo impact of an n-3 PUFA-defi cient diet on expression of the main glucose transporters of rat cerebral cortex (endothelial 55-kDa GLUT1, astrocytic 45-kDa GLUT1, and neuronal GLUT3); and 2) the in vitro impact of the three main long-chain n-6 and n-3 PUFAs, arachidonic acid (20:4n-6), eicosapentaenoic acid (20:5n-3) and DHA, on the fatty acid composition of membrane phospholipids and glucose uptake in two models of rat brain endothelial cells (primary cultures (RBEC), and immortalized cell line RBE4). In vivo study Rats raised with a n-3 PUFA defi cient diet throughout one generation were compared with rats fed a diet with adequate amounts of n-6 and n-3 PUFA. The fatty acid profi le of brain microvessels was determined in order to identify the alterations in n-6 and n-3 PUFA in endothelial cells compared to their profi le in neural cells from the cerebral cortex. The main glucose transporters were quantifi ed by western immunoblotting and by real time quantitative RT-PCR. Specifi c binding of cytochalasin B to GLUT1 of isolated microvessels was also determined. In vitro study The three PUFA studied were added to the culture medium (15μM) as sodium salts on the fi rst day of culture and until the cells were used. Glucose uptake was measured on monolayers of RBEC and RBE4 cells using the non-metabolisable radiolabelled glucose analogue 3-o-methylglucose ([3H]-3-o-MG). In vivo data showed that the 55-kDa GLUT1 protein quantity decreased by 25% in the n-3 PUFA-defi cient microvessels, as did 45 kDa-GLUT1 in the homogenate (30% decrease). Results from cytochalasin B binding confi rmed these data, showing a lower level of its maximum binding to GLUT1. However, GLUT3 protein quantity did not change as GLUT1 and GLUT3 mRNA level. In vitro data demonstrated that both cerebral endothelial cells had low n-6 (mainly 20:4n-6) and n-3 (mainly 22:6n-3) PUFA concentrations under standard conditions of culture. RBEC and RBE4 cells grown in medium supplemented with 20:4n-6, 20:5n-3 or 22:6n-3 (15 μM, physiological concentrations), avidly incorporated these PUFAs into their membrane phospholipids to approach the contents of cerebral microvessels of control rats (considered as physiological references). However RBE4 cells did not incorporate suffi cient 20:4n-6 compared to physiological concentrations. Supplementation with 20:5n-3 and 22:6n-3 increased the basal glucose transport in RBEC ([3H]-3-O-methylglucose uptake) by 50% and 35% respectively, while 20:4n-6 had no effect. On the other hand, none of the PUFA supplements had a signifi cant effect on glucose uptake by RBE4. We demonstrated that incorporation of n-3 long-chain PUFAs in RBEC membranes acts on glucose transport activity. We suggest that the decreased glucose utilization in the cerebral cortex of n-3 PUFA-defi cient rats is in part due to reduced amounts of the two GLUT1 isoforms, possibly issuing from post-transcriptional down-regulation of GLUT1 protein synthesis. In vitro studies suggest that n-3 PUFA can directly modulate the activity of glucose transport in endothelial cells by altering their membrane phospholipid content.

Metabolic Syndrome: Effects of n‐3 PUFAs on a Model of Dyslipidemia, Insulin Resistance and Adiposity

Both genetic and environmental factors (e.g. nutrition, life style) contribute to the development of the plurimetabolic syndrome, which has a high prevalence in the world population. Dietary n-3 PUFAs specially those from marine oil (EPA and DHA) appear to play an important role against the adverse effects of this syndrome. The present work examined the effectiveness of fish oil (FO) in reversing or improving the dyslipidemia, insulin resistance and adiposity induced in rats by long-term feeding a sucrose-rich diet (SRD). We studied several metabolic and molecular mechanisms involved in both lipid and glucose metabolisms in different tissues (liver, skeletal muscle, fat pad) as well as insulin secretion patterns from perifused islets under the stimulation of different secretagogues. Dietary FO reverses dyslipidemia and improves insulin action and adiposity in the SRD fed rats. FO reduces adipocytes cell size and thus, the smaller adipocytes are more insulin sensitive and the release of fatty acids decreases. In muscle, FO normalizes both the oxidative and non-oxidative glucose pathways. Moreover, FO modifies the fatty acid composition of membrane phospholipids. In isolated beta cells, lipid contents and glucose oxidation return to normal. All these effects could contribute to the normalization of glucose-stimulated insulin secretion and muscle insulin insensitivity.

The Sensitivity of Yeast Mutants to Oleic Acid Implicates the Peroxisome and Other Processes in Membrane Function

The peroxisome, sole site of beta-oxidation in Saccharomyces cerevisiae, is known to be required for optimal growth in the presence of fatty acid. Screening of the haploid yeast deletion collection identified approximately 130 genes, 23 encoding peroxisomal proteins, necessary for normal growth on oleic acid. Oleate slightly enhances growth of wild-type yeast and inhibits growth of all strains identified by the screen. Nonperoxisomal processes, among them chromatin modification by H2AZ, Pol II mediator function, and cell-wall-associated activities, also prevent oleate toxicity. The most oleate-inhibited strains lack Sap190, a putative adaptor for the PP2A-type protein phosphatase Sit4 (which is also required for normal growth on oleate) and Ilm1, a protein of unknown function. Palmitoleate, the other main unsaturated fatty acid of Saccharomyces, fails to inhibit growth of the sap190delta, sit4delta, and ilm1delta strains. Data that suggest that oleate inhibition of the growth of a peroxisomal mutant is due to an increase in plasma membrane porosity are presented. We propose that yeast deficient in peroxisomal and other functions are sensitive to oleate perhaps because of an inability to effectively control the fatty acid composition of membrane phospholipids.