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At least 433 records · Page 24Linked to original sources
PubMed1993

Mechanism of fluorescent fatty acid transfer from adipocyte fatty acid binding protein to membranes.

Adipocyte fatty acid binding protein (A-FABP) is a 15-kDa protein found in high abundance in the cytosol of adipose cells. To better understand the role of this protein in intracellular free fatty acid (ffa) transport, the mechanism of ffa transfer from A-FABP to model membranes was examined by monitoring the transfer of fluorescent anthroyloxy ffa (AOffa) to small unilamellar phospholipid vesicles, using a resonance energy transfer assay. Structural features of ffa that increase aqueous solubility, such as shorter chain length and unsaturation, did not increase the AOffa transfer rate. In addition, solution conditions that increase the aqueous solubility of ffa, such as decreasing ionic strength and increasing pH, had little effect on AOffa transfer from A-FABP to membranes. These results suggest that AOffa do not transfer through the aqueous phase. The small entropic contribution to the free energy of the transfer process provides further evidence that AOffa may not travel through the surrounding aqueous environment when transferred from A-FABP to phospholipid membranes. Finally, the rate of AOffa transfer from A-FABP was directly dependent on the concentration of the acceptor membranes. These studies suggest that AOffa transfer from A-FABP to phospholipid vesicles may occur via transient collisional interactions between the protein and membranes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed2004

New concepts of cellular fatty acid uptake: role of fatty acid transport proteins and of caveolae.

Efficient uptake and channelling of long-chain fatty acids (LCFA) are critical cell functions. Evidence is emerging that proteins are important mediators of LCFA-trafficking into cells and various proteins have been suggested to be involved in this process. Amongst these proteins is a family of membrane-associated proteins termed fatty acid transport proteins (FATP). So far six members of this family, designated FATP 1-6, have been characterized. FATP 1, 2 and 6 show a highly-conserved AMP-binding region that participates in the activation of very-long-chain fatty acids (VLCFA) to form their acyl-CoA derivatives. The mechanisms by which FATP mediate LCFA uptake are not well understood, but several studies provide evidence that uptake of LCFA across cellular membranes is closely linked to acyl-CoA synthetase activity. It is proposed that FATP indirectly enhance LCFA uptake by activating VLCFA to their CoA esters, which are required to maintain the typical structure of lipid rafts in cellular membranes. Recent work has shown that the structural integrity of lipid rafts is essential for cellular LCFA uptake. This effect might be exerted by proteins, e.g. caveolin-1 and FAT/CD36, that use lipid rafts as platforms and bind or transport LCFA. The proposed molecular mechanisms await further experimental investigation.

CD36 Antigens↗
PubMed1996

Ferriheme and ferroheme are isosteric inhibitors of fatty acid binding to rat liver fatty acid binding protein.

In addition to fatty acids, liver fatty acid binding protein (L-FABP) also interacts with ferriheme, which it binds with an affinity approximately one order of magnitude greater than that for oleic acid. We have, therefore, examined the effect of ferroheme and ferriheme on the binding of oleate to rat L-FABP also called heme-binding protein. Both oxidation states of heme behaved as isosteric inhibitors for the binding of the fatty acid confirming a common binding site. The reduced form of heme (Fe(II)) is a threefold better competitor of oleate binding than ferriheme. To show whether the diffusion of heme would be affected by the presence of the binding protein, we measured the effect of the fatty acid binding protein on the diffusional flux of a water-soluble heme derivative, iron-deuteroporphyrin. The diffusional flux of iron-deuteroporphyrin did not change in the presence of the protein. This suggested that the binding affinity of fatty acid binding protein for iron-deuteroporphyrin is too great to allow rapid equilibrium between bound and unbound ligand across the system in an appropriate time frame.

Animals↗
PubMed2001

Dietary trans fatty acids combined with a marginal essential fatty acid status during the pre- and postnatal periods do not affect growth or brain fatty acids but may alter behavioral development in B6D2F(2) mice.

The objective of this study was to investigate whether dietary trans fatty acids (TFA) during the pre- and postnatal periods would exacerbate the effects of marginal essential fatty acid (EFA) status on growth, brain long-chain polyunsaturated fatty acids (LC-PUFA) and behavioral development in B6D2F(2) mice. Pregnant B6D2F(1) females were randomly assigned to one of the following three diets: marginal EFA plus 22% trans 18:1 (mEFA + TFA); marginal EFA (mEFA); and control (CON). The total 18:1 content in all diets was similar. The offspring were weaned and maintained on the same diets. Both the mEFA and mEFA + TFA groups had reduced growth and brain weight compared with CON, but did not differ from one another. As expected, the mEFA and mEFA + TFA groups had reduced docosahexaenoic acid [DHA; 22:6(n-3)]) and increased 22:5(n-6) concentrations in brain phosphatidylcholine (PC) and phosphatidylethanolamine (PE) compared with the CON group, but again did not differ from one another. Reversal learning in the T-water maze was significantly slower in the mEFA + TFA groups compared with the mEFA group and both were slower than the CON group. These findings illustrate that TFA combined with a marginal EFA status do not exacerbate the effects of marginal EFA status on growth or brain LC-PUFA. However, long-term effects of dietary TFA during the pre- and postnatal period on behavioral development and neural function should be investigated in future studies.

Animals↗
PubMed1998

Chronic dietary n-3 polyunsaturated fatty acids deficiency affects the fatty acid composition of plasmenylethanolamine and phosphatidylethanolamine differently in rat frontal cortex, striatum, and cerebellum.

As chronic consumption of a diet devoid of n-3 fatty acid induced modification of neurotransmission pathways in the frontal cortex of rats, plasmalogen alteration could occur in this area. Because of the propensity to facilitate membrane fusion, plasmenylethanolamine (PmE), a major plasmalogen of brain, may be involved in synaptic transmission. Female rats were fed diet containing peanut oil [(n-3)-deficient diet] through two generations. Two weeks before mating, half of the female rats of the second generation received a diet containing peanut oil and rapeseed oil (control group). The distribution and acyl composition of major phospholipids, phosphatidylethanolamine and PmE, were measured in the frontal cortex, striatum, and cerebellum of the male progeny of the two groups at 60 d of age. The n-3 polyunsaturated fatty acid (PUFA) deficiency had no effect on the distribution of phospholipids in all brain regions but affected their acyl composition differently. The level of 22:6n-3 was significantly lower and compensated for by higher levels of n-6 fatty acids in all regions and phospholipids studied. However, docosahexaenoic acid, being more concentrated in the PmE of frontal cortex, is also more decreased in the n-3-deficient rats compared to the striatum. By contrast, striatum PmE has retained more 22:6n-3 than PmE of the other regions. In addition, the increase of n-6 PUFA was significantly lower in frontal cortex PmE compared to the striatum and cerebellum PmE. In association with altered neurotransmission observed in frontal cortex of n-3-deficient rats, our results suggest that frontal cortex PmE might be more affected in chronically alpha-linolenic-deficient rats. However, by retaining 22:6n-3, striatum PmE could be most resilient.

Animals↗
PubMed1999

Alcohol consumption in rhesus monkeys depletes tissues of polyunsaturated fatty acids and alters essential fatty acid metabolism.

Rhesus monkeys that were maintained on an adequate diet but with low levels of essential fatty acids (1.4 en% linoleic, 18:2n-6, and 0.08 en%, linolenic acid, 18:3n-3) became depleted of 20:4n-6, and 22: 6n-3 in their livers, plasma lipoproteins, and erythrocytes during an 18-month period of alcohol exposure (2.6 g kg(-1) day(-1)). Monkeys that consumed alcohol also had higher plasma concentrations of 4-hydroxynonenal compared to controls. The metabolism of 18:2n-6 and 18:3n-3 were evaluated in both groups of animals using deuterium-labeled substrates over a 9-day period. Alcohol consumption did not appear to have an effect on the absorption of either 2H5-18:2n-6 or 2H5-18:3n-3 ethyl esters into the circulation after a single oral dose. However, there was a greater enrichment of deuterium in the biosynthesized fatty acids, 20:4n-6 and 22:6n-3, in the plasma of the monkeys exposed to alcohol compared to controls. These results suggest that chronic alcohol exposure may lead to a stimulation of the rate at which long-chain polyunsaturated fatty acids are biosynthesized to compensate for an increase in lipid peroxidation.

Aldehydes↗
PubMed1997

Time-resolved fluorescence of intestinal and liver fatty acid binding proteins: role of fatty acyl CoA and fatty acid.

The effect of fatty acyl CoA and fatty acid on the solution structure and dynamics of two intestinal enterocyte fatty acid binding proteins, intestinal (I-FABP) and liver (L-FABP), was examined by time-resolved fluorescence of FABP aromatic amino acid residues. I-FABP Trp displayed two rotational correlation times, 6.6 and 0.4 ns. reflecting motion of the protein as a whole and segmental mobility of Trp. Neither oleoyl CoA, oleic acid, nor CoASH altered overall I-FABP rotational correlation time. However, oleic acid and CoASH increased I-FABP Trp segmental mobility, while oleoyl CoA and CoASH decreased I-FABP Trp limiting anisotropy (order). The angle of I-FABP Trp "wobbling in a cone" was increased by ligands in the order oleoyl CoA > CoASH > oleic acid. L-FABP Trp segmental mobility. L-FABP overall rotational motion, in contrast to that of I-FABP, was significantly increased by ligands in the order oleoyl CoA > oleic acid > CoASH. cis-Parinaric acid and cis-parinaroyl CoA bound to L-FABP also reflected overall L-FABP motion but yielded longer rotational correlation times, 8.2 and 10.7 ns, than the respective apo-FABPs. Such effects were not observed with I-FABP. Finally, both cis-parinaric acid and cis-parinaroyl CoA were much less ordered in the I-FABP ligand binding site than with L-FABP. These observations suggest that the rotational dynamics of L-FABP and its conformation are more sensitive to ligands than I-FABP. Further, ligands such as fatty acids, fatty acyl CoAs, and/or CoASH differentially modulate the I-FABP and L-FABP dynamics, and the ligand binding sites of these proteins differ in their ability to order the ligands.

Acyl Coenzyme A↗
PubMed1994

Capillary gas chromatography of underivatized fatty acids with a free fatty acid phase column and a programmed temperature vaporizer injector.

Underivatized fatty acids occurring in lipids of a number of biological specimens (blood plasma, tissues, food) were studied using a capillary column with a chemically bonded free fatty acid phase and a programmed temperature vaporizer. Non-linear calibration dependences were obtained for almost all the acids at lower concentrations because of losses in the column, non-linearity increasing with increasing carbon number and degree of unsaturation. Sample introduction at temperatures below the solvent boiling point eliminates losses in the injector. The lower recovery of long-chain polyunsaturated acids is caused by interactions occurring in the column. Some critical pairs remain unresolved in the underivatized form (18:1n9-18:1n7, 20:4n6-20:3n3), whereas the corresponding methyl esters exhibit baseline resolution.

Chromatography, Gas↗
PubMed1993

Regulation of pathways of extramitochondrial fatty acid oxidation and liver fatty acid-binding protein by long-chain monocarboxylic fatty acids in hepatocytes. Effect of inhibition of carnitine palmitoyltransferase I.

The regulation of the extramitochondrial fatty acid oxidation pathways located in the peroxisomes and the endoplasmic reticulum is not fully understood. Although both long-chain dicarboxylic fatty acids, which are poorly metabolized in hepatocytes, and non-beta-oxidizable fatty acid analogs induce peroxisomal beta-oxidation and liver fatty acid-binding protein (L-FABP) by a pretranslational mechanism, monocarboxylic long-chain fatty acids, which are rapidly esterified and oxidized, do not. To establish whether impaired utilization and, hence, sustained intracellular levels of monocarboxylic long-chain fatty acids increase their efficacy as inducers, the effect of oleic acid on cytochrome P-450 4A1, peroxisomal beta-oxidation, and L-FABP during inhibition of mitochondrial beta-oxidation was determined. In primary hepatocyte cultures, oleic acid had no inducing effect, but in the presence of 2-tetradecylglycidic acid (TDGA), an inhibitor of carnitine palmitoyltransferase I, it induced P-450 4A1, peroxisomal beta-oxidation, and L-FABP pretranslationally. An increase in peroxisomal beta-oxidation was also noted in the presence of etomoxir, another inhibitor of carnitine palmitoyltransferase I. Exposure of hepatocytes to TDGA for 1 h led to an expected decrease in incorporation of radiolabel from [1-14C]oleate into CO2 and water-soluble products. In contrast, long-term exposure to TDGA increased incorporation of [1-14C]oleate into oxidation products, most likely due to an adaptive induction of peroxisomal beta-oxidation. Both acute and long-term exposure of hepatocytes to TDGA decreased incorporation of oleic acid into triglycerides, an effect that may have contributed to the intracellular accumulation of fatty acids. These results provide support for a mechanism by which long-chain fatty acids or specific metabolites, including long-chain acyl-CoA esters and long-chain dicarboxylic acids, act as signals in the induction of P-450 4A1, peroxisomal beta-oxidation, and L-FABP under conditions in which long-chain fatty acids accumulate due to impaired entry into the mitochondrial beta-oxidation pathway.

Acyl-CoA Oxidase↗
PubMed2006

Intestinal bifidobacteria that produce trans-9, trans-11 conjugated linoleic acid: a fatty acid with antiproliferative activity against human colon SW480 and HT-29 cancer cells.

Bifidobacterium breve species of human intestinal origin have the ability to synthesize cis-9, trans-11 (c9, t11) conjugated linoleic acid (CLA) from free linoleic acid. In this study, the ability of Bifidobacterium species to isomerize C(18) polyunsaturated fatty acids was investigated, and the antiproliferative activities of the two main microbially produced CLA isomers were assessed. Linoleic acid was converted principally to c9, t11 CLA and lesser amounts of t9, t11 CLA, whereas c9, t11 CLA was converted mainly to t9, t11 CLA. Likewise, t10, c12 CLA was converted principally to t9, t11 CLA, which was incorporated into the bacterial cell membranes. To examine the antiproliferative effect of the two main CLA isomers formed, SW480 and HT-29 human colon cancer cells were cultured in the presence of c9, t11 CLA and t9, t11 CLA. The t9, t11 CLA had a more potent antiproliferative effect than c9, t11 CLA. It is tempting to suggest that the ability of Bifidobacterium to produce such bioactive metabolites may be associated with the beneficial effects of bifidobacteria present in the human gastrointestinal tract.

Antineoplastic Agents↗
PubMed1992

Cellular interactions between n-6 and n-3 fatty acids: a mass analysis of fatty acid elongation/desaturation, distribution among complex lipids, and conversion to eicosanoids.

The biologic effect of eicosanoids depends in large measure upon the relative masses in tissues of eicosanoids derived from the n-6 fatty acids, dihomogammalinolenic acid and arachidonic acid, and the n-3 fatty acid, eicosapentaenoic acid. Generation of this tissue balance is related to the relative cellular masses of these precursor fatty acids, the competition between them for entry into and release from cellular phospholipids, and their competition for the enzymes that catalyze their conversion to eicosanoids. In order to better understand these processes, we studied the cellular interactions of n-6 and n-3 fatty acids using an essential fatty acid-deficient, PGE-producing, mouse fibrosarcoma cell line, EFD-1. Unlike studies using cells with endogenous pools of n-6 and n-3 fatty acids, the use of EFD-1 cells enabled us to examine the metabolic fate of each family of fatty acids both in the presence and in the absence of the second family of fatty acids. Thus, the specific effects of one fatty acid family on the other could be directly assessed. In addition, we were able to replete the cells with dihomogammalinolenic acid (DHLA), arachidonic acid (AA), and eicosapentaenoic acid (EPA) of known specific activities; thus the masses of cellular DHLA, AA, and EPA, and their metabolites, PGE1, PGE2, and PGE3, respectively, could be accurately quantitated. The major findings of this study were: 1) n-6 fatty acids markedly stimulated the elongation of EPA to 22:5 whereas n-3 fatty acids inhibited the delta 5 desaturation of DHLA to AA and the elongation of AA to 22:4; 2) n-6 fatty acids caused a specific redistribution of cellular EPA from phospholipid to triacylglycerol; 3) n-3 fatty acids reduced the mass of DHLA and AA only in phosphatidylinositol whereas n-6 fatty acids reduced the mass of EPA to a similar extent in all cellular phospholipids; and 4) n-3 fatty acids caused an identical (33%) reduction in the bradykinin-induced release of PGE1 and PGE2, whereas n-6 fatty acids stimulated PGE3 release 2.3-fold. Together, these highly quantitative metabolic data increase our understanding of the regulation of both the cellular levels of DHLA, AA, and EPA, and their availability for eicosanoid synthesis. In addition, these findings provide a context for the effective use of these fatty acids in dietary therapies directed at modulation of eicosanoid production.

8,11,14-Eicosatrienoic Acid↗
PubMed1984

Specific inactivation of hepatic fatty acid hydroxylases by acetylenic fatty acids.

The terminal acetylenic analogue of lauric acid, 11-dodecynoic acid (11-DDYA), specifically inactivates hepatic cytochrome P-450 enzymes that catalyze omega- and omega-1-hydroxylation of lauric acid. The inactivation, as required for a suicidal process, is NADPH- and time-dependent and follows pseudo-first order kinetics. In contrast, 11-DDYA causes no measurable change in the spectroscopically-measured concentration of cytochrome P-450 or in the N-demethylation of benzphetamine or N-methyl p-chloroaniline. 10-Undecynoic acid is as effective a suicide substrate for fatty acid hydroxylases as 11-DDYA but 11-dodecenoic acid is much less effective. 11-DDYA is able to completely inhibit omega-hydroxylation but suppresses no more than 50% of omega-1-hydroxylation despite the fact that both activities are completely inactivated by 1-aminobenzotriazole. At least three hepatic cytochrome P-450 fatty acid hydroxylases, one omega-hydroxylase and two omega-1-hydroxylases, are required by these results. The construction of suicide substrates that specifically inactivate cytochrome P-450 fatty acid hydroxylases provides a new experimental probe of the physiological role of this process.

Animals↗
PubMed1989

Effects of prilled fatty acids and calcium salts of fatty acids on rumen fermentation, nutrient digestibilities, milk production, and milk composition.

Lactating Holstein cows averaging 193 d postpartum and fitted with rumen cannulae were used in two experiments to investigate the effects of supplementing Ca salts of fatty acids or prilled fatty acids to the diet on fermentation in the rumen, apparent total tract nutrient digestibility, milk production, and milk composition. Cows were fed ad libitum total mixed diets consisting of 45% concentrate and 55% forage. Treatments in Experiment 1 were: 1) control, 2) control plus 680 g/cow per d of Ca salts of fatty acids, 3) control plus 680 g/cow per d of prilled fatty acids, or 4) control plus 907 g/cow per d of prilled fatty acids. Treatments in Experiment 2 were: 1) control, 2) control plus 553 g/cow per d of Ca salts of fatty acids, or 3) control plus 454 g/cow per d of prilled fatty acids. Data suggest that Ca salts of fatty acids and prilled fatty acids are inert in the rumen and do not greatly alter fermentation in the rumen, apparent total tract digestibilities of DM, organic matter, ADF, NDF, and CP, or milk composition when fed at recommended amounts of 3 to 4% of the DM intake. The fact that milk production was not increased in these experiments by feeding Ca salts of fatty acids and prilled fatty acids may be attributed to the use of medium to low producing cows that were past the peak of milk production. Additional experiments are needed to obtain information about feeding these sources of supplemental fat to high producing cows during the early stages of lactation.

Animals↗
PubMed1995

Patients with anorexia nervosa demonstrate deficiencies of selected essential fatty acids, compensatory changes in nonessential fatty acids and decreased fluidity of plasma lipids.

The objective of this study was to assess the essential fatty acid status of patients with anorexia nervosa. Blood was collected from eight fasting female anorexia nervosa patients with a mean of 81% ideal body weight. Fatty acid composition of phospholipids, nonesterified fatty acids, triglycerides and cholesteryl esters of plasma were determined by capillary gas chromatography to indicate polyunsaturated fatty acids status compared with 19 healthy female adults < 25 y old. Subjects with anorexia nervosa showed polyunsaturated fatty acid deficiencies in plasma phospholipids different from simple nutritional essential fatty acid deficiency or chronic malnutrition. The phospholipid profile showed significantly lower (n-6) and (n-3) elongation and desaturation products, and elevated short-chain saturated, short-chain monounsaturated, branched-chain and odd-chain fatty acids. These elevations indicate enhancement of biosynthesis of alternative fatty acids that only partially compensated for the loss of polyunsaturated fatty acids in providing membrane "fluidity." Calculated mean melting point of the fatty acids of phospholipids in patients with anorexia nervosa was elevated 7.7 degrees C above normal values. These results demonstrate that patients with anorexia nervosa have deficiencies of selected essential fatty acids, compensatory changes in nonessential fatty acids and decreased fluidity of plasma lipids.

Adolescent↗