Characteristics of Lysophosphatidylcholine in Its Inhibition of Taurine Uptake by Human Intestinal Caco-2 Cells

The characteristics of lysophosphatidylcholine (LPC) in its inhibition of the taurine uptake by human intestinal Caco-2 cells were investigated. By treating the cells with 200 μM of LPC, the taurine uptake was rapidly decreased by approximately 60%. This decrease was accompanied by an increase in the K _m value for the uptake. A rapid uptake of LPC itself by the cells was also observed. The inhibitory activity of LPC was specific to the uptake of taurine and certain amino acids, while the uptake of glucose, glutamic acid and peptide (glycylglutamine) was not affected by LPC. The activity was dependent on the structure of a polar head and the bound fatty acid. The phosphorylcholine residue was likely to have played an important role, and surface active LPC with fatty acids of C14 or longer was highly inhibitory. These results suggest that the interaction of LPC with the taurine transporter in the intestinal cell membrane was the cause of the reduced taurine uptake.     

Mechanical Force and Cytoplasmic Ca2+ Activate Yeast TRPY1 in Parallel

Diets supplemented with n-3 polyunsaturated fatty acids can promote lipid peroxidation and the propagation of oxygen radicals. These effects can be prevented by taurine, a functional ingredient with antioxidant properties. Here, we examined whether there is a correlation between transepithelial taurine transport, on the one hand, and membrane fatty acid composition and peroxidation in intestinal Caco-2 cells, on the other. Differentiated Caco-2 cells were maintained for 10 days, from the day of confluence, in control conditions or in a medium enriched with docosahexaenoic acid (DHA, 100 μmol/l), taurine (10 mmol/l) or DHA plus taurine. Incubation of the monolayers in a medium enriched with DHA increased the incorporation of this fatty acid into the brush-border membrane, at the expense of total n-6 fatty acids (C20:2n-6, C20:3n-6 and C22:4n-6). This was paralleled by increased membrane lipid peroxidation, which was partially limited by the addition of taurine. Transepithelial taurine transport was estimated from taurine uptake and efflux kinetic parameters at apical and basolateral domains. Cell incubation with DHA increased basolateral taurine uptake through an increase in V _max, whereas incubation with taurine downregulated basolateral uptake as occurred for apical taurine transporter. Moreover, addition of DHA reduced the apical downregulation effect exerted on taurine transport by taurine incubation. Our results suggest that the oxidative status of epithelial cells regulates taurine transport, thus satisfying antioxidant cellular requirements.     

Identification of a taurine transport inhibitory substance in sesame seeds

An ethanol extract from sesame seeds inhibited the taurine uptake in human intestinal epithelial Caco-2 cells. The uptake of such alpha-amino acids as leucine and glutamic acid was not inhibited by the extract, indicating that this inhibition is specific to the taurine uptake. The unknown inhibitor in the sesame extract was purifled by reversed-phase HPLC by monitoring the inhibitory effect on taurine uptake. The isolated substance was identified as lysophosphatidylcholine, linoleoyl (Lyso-PC), by NMR and MS analysis. Lyso-PC inhibited the taurine uptake in a dose-dependent manner with an IC50 value of approximately 200 microM. Although Lyso-PC is known to be a surface active and cell lytic compound, neither damage nor loss of integrity of the Caco2 cell monolayer was apparent after treating with 200 microM Lyso-PC. Inhibition was observed by incubating cells with Lyso-PC for only 1 min prior to the uptake experiments. These results suggest the direct effect of Lyso-PC on the cell membrane to be the main mechanism for this inhibition. Lyso-PC may play a role in the regulation of certain intestinal transporters.     

Extracellular metabolism-dependent uptake of lysolipids through cultured monolayer of differentiated Caco-2 cells

Glycerophospholipids are known to be hydrolyzed in the intestinal lumen into free fatty acids and lysophospholipids that are then absorbed by the intestinal epithelial cells. A monolayer of enterocyte-differentiated Caco-2 cell is often used to assess the intestinal bioavailability of nutrients. In this study, we examined how differentiated Caco-2 cells process lysoglycerolipids such as lysophosphatidylcholine (LPC). Our findings were twofold. (1) Caco-2 cells secreted both a lysophospholipase A-like enzyme and a glycerophosphocholine-phosphodiesterase enzyme into the apical, but not basolateral, lumen, suggesting that food-derived LPC is converted to a free fatty acid, sn-glycerol-3-phosphate, and choline through two sequential enzymatic reactions in humans. The release of the latter enzyme was differentiation-dependent. (2) Fatty acid-releasing activities toward exogenous fluorescent LPC, lysophosphatidic acid and monoacylglycerol were shown to be higher on the apical membranes of Caco-2 cells than on the basolateral membranes. These results suggest that human intestinal epithelial cells metabolize lysoglycerolipids by two distinct mechanisms involving secreted or apical-selective expression of metabolic enzymes.     

Effect of Membrane Polyunsaturation on Carrier-Mediated Transport in Cultured Retinoblastoma Cells: Alterations in Taurine Uptake

Neural cell membranes naturally contain a large amount of polyunsaturated fatty acid, but the functional significance of this is unknown. An increase in membrane polyunsaturation has been shown previously to affect the high-affinity transport systems for choline and glycine in cultured human Y79 retinoblastoma cells. To test the generality of membrane polyunsaturation effects on transport, we investigated the uptake of other putative neurotransmitters and amino acids by these cells. Taurine, glutamate, and leucine were taken up by both high- and low-affinity transport systems, whereas serine, gamma-aminobutyrate, and alpha-aminoisobutyrate were taken up only by low-affinity systems. The high-affinity taurine and glutamate and low-affinity serine uptake systems were Na+ dependent. Arachidonic acid (20:4) supplementation of Y79 cells produced enrichment of all the major microsomal phosphoglycerides with 20:4, while docosahexaenoic acid (22:6) supplementation produced large increases in the 22:6 content of all fractions except the inositol phosphoglycerides. Enrichment with these polyunsaturated fatty acids facilitated taurine uptake by lowering the K'm of its high-affinity transport system. By contrast, enrichment with oleic acid did not affect taurine uptake. Glutamate, leucine, serine, gamma-aminobutyrate, and alpha-aminoisobutyrate uptake were not affected when the cells were enriched with any of these fatty acids. These findings demonstrate that only certain transport systems are sensitive to the polyunsaturated fatty acid content of the retinoblastoma cell membrane. The various transport systems either respond differently to changes in membrane lipid unsaturation, or they are located in lipid domains that are modified to different extents by changes in unsaturation.     

Dietary oxidized fatty acids: an atherogenic risk?

Previous studies have suggested that heated fat that contains oxidized fatty acids in the diet might contribute to the presence of oxidized components in circulating lipoproteins. On the other hand, studies in our laboratory showed that cultured cells such as smooth muscle cells take up oxidized fatty acids poorly. Because intestinal cells are morphologically quite distinct, we studied the uptake of oxidized linoleic acid by Caco-2 and smooth muscle cells (control). When 16-day-old Caco-2 cells were incubated with oxidized linoleic acid (ox-linoleic acid), its uptake was comparable to that of unoxidized linoleic acid (unox-linoleic acid) or that of oleic acid (40;-58, 70, and 55%, respectively). In contrast, the uptake of ox-linoleate by smooth muscle cells was about 3%. To determine whether the brush border structure of Caco-2 cells was responsible for increased uptake of oxidized fatty acids, we compared uptake in 4- and 16-day-old cells. The uptake of unox-linoleate and oleic acid (18:1) was comparable for the 4- and 16-day cells. In addition, saturation and competition experiments showed that the uptake of ox-linoleate by Caco-2 cells is not saturable even at 150 microm and that this uptake is diluted in the presence of unox-linoleate. In esterification experiments utilizing rat intestinal microsomes, we show that both ox- and unox-linoleate are esterified equally well.In summary, dietary oxidized fatty acids can be absorbed by the intestine and incorporated into lipoproteins and could potentially impose an oxidative stress and exacerbate atherogenesis.     

Polyene antibiotic amphotericin B in monomolecular layers: spectrophotometric and scanning force microscopic analysis

The effect of cytokines on the taurine uptake by human intestinal epithelial Caco-2 cells was investigated. Among the various cytokines tested, tumor necrosis factor alpha (TNF-alpha) markedly increased the taurine uptake by Caco-2 cells, resulting in an increase in the intracellular taurine level. TNF-alpha did not induce up-regulation of the taurine uptake in hepatic HepG2, renal human embryo kidney 293, and macrophage-like THP-1 cells. The uptake of glycine, L-leucine, and L-glutamic acid by Caco-2 cells was not affected by TNF-alpha. A kinetic analysis of the taurine uptake by TNF-alpha-treated Caco-2 cells suggests that this up-regulation was associated with both an increase in the amount of the taurine transporter (TAUT) and an increase in its affinity. TNF-alpha-treated cells showed a higher mRNA level of the TAUT than did the control cells.     

The overall fatty acid absorption controlled by basolateral chylomicron excretion under regulation of p-JNK1

Suppression of fatty acid absorption is one goal to fight obesity. However, the responsible molecular mechanism is poorly understood. Aim of the present study was the search for the key regulator of the overall fatty acid absorption mechanism and its pharmaceutical modulation. As experimental tool we employed the polarized human intestinal tumor derived cell line CaCo2. Here we showed that influx of fatty acids is mediated by an apical heterotetrameric plasma membrane protein complex of which the calcium-independent membrane phospholipase A₂ (iPLA₂ß) is one constituent. The newly synthesized bile acid-phospholipid conjugate ursodeoxycholate-lysophosphatidylethanolamide (UDCA-LPE) blocked iPLA₂ß, which structurally disrupted the fatty acid-uptake complex. Furthermore, the inhibition of iPLA₂ß lead to reduction of cytosolic lysophosphatidylcholine (LPC) production which suppressed p-JNK1, as a central regulator of metabolism. In a concerted action low p-JNK1 levels prohibited synthesis of the members of the fatty acid uptake complex as well as of apolipoprotein B and the connected members of the basolateral vesicular chylomicron excretion machinery, thereby inhibiting cellular lipid excretion. The basolateral chylomicron release was shown to determine the overall fatty acid-absorption capacity as rate limiting step, whereas apical uptake replenishes the cellular stores, enabling continuous transcellular movement of fatty acids. In conclusion, the UDCA-LPE mediated inhibition of p-JNK1 represents a powerful tool to control intestinal absorption of fatty acids and, thus may be employed as a drug to treat obesity.     

Spectrum of effects of dietary long-chain fatty acids on rat intestinal glucose and lipid uptake

Isocaloric modification in the ratio of dietary polyunsaturated-to-saturated fatty acids influences intestinal uptake of actively and passively transported nutrients. This study was undertaken to determine which dietary fatty acid was responsible for these alterations in absorption. Adult female rats were fed isocaloric semisynthetic diets high in palmitic and stearic acids (SFA), oleic acid (OA), linoleic acid (LA), or linolenic acid (LNA). An in vitro technique was used to measure the uptake of varying concentrations of glucose as well as a series of fatty acids and cholesterol. Jejunal uptake of 40 mM glucose was highest in rats fed SFA and lowest in those fed LA; ileal glucose uptake was similar in OA, LA, and LNA, but was lowest in SFA. Jejunal uptake of medium-chain fatty acids (8:0-12:0) was higher in OA than in other diet groups; ileal uptake of medium-chain fatty acids was unaffected by diet. Jejunal and ileal uptake of 18:2 was higher in LNA than in SFA or OA; the uptake of the other long-chain saturated or unsaturated fatty acids was unchanged by diet. The ileal but not the jejunal uptake of cholesterol was increased in LA as compared with SFA or OA, and reduced in LNA as compared with LA. These transport changes were not explained by differences in the animals' food consumption, body weight gain, intestinal mass, or mucosal surface area. We postulate that these diet-induced transport alterations may be mediated via changes in brush border membrane phospholipid fatty acyl composition. Thus, intestinal transport of nutrients may be varied by isocaloric changes in the dietary content of individual fatty acids.     

Ecto-lysophospholipase C controls lysophospholipid uptake and metabolism in porcine kidney epithelial cell line LLC-PK1

Lysophosphatidylcholine (LPC) has diverse biological activities through different mechanisms including its conversion into other types of lipid mediators such as lysophosphatidic acid and 2-arachidonoylglycerol. Previously, we found that a large portion of the fluorescent analog of alkyl type LPC (Bodipy-lysoPAF) on porcine kidney epithelial cells (LLC-PK1) was degraded to monoalkylglycerol by lysophospholipase C-like activity and then quickly internalized into the cells. In this study, we investigated whether exogenous fluorescently labeled LPC (NBD-LPC) itself was also metabolized and internalized by a similar mechanism. LLC-PK1 cells converted NBD-LPC to either NBD-MG, possibly due to lysophospholipase C-like activity of ecto-nucleotide pyrophosphatase/phosphodiesterase-6, or to free fatty acid (FA), due to lysophospholipase activity in the culture medium at both sites. The resultant NBD-MG was further degraded to NBD-FA by lipase activity before or after its uptake into the cells, and a portion of NBD-FA was finally released into the culture medium on the opposite side.     

The signal molecule lysophosphatidylcholine in Eschscholzia californica is rapidly metabolized by reacylation

In cultured cells of California poppy (Eschscholzia californica), lysophosphatidylcholine (LPC) triggers a signal path that finally induces alkaloid biosynthesis. LPC is transiently generated by elicitor-activated phospholipase A(2) of the plasma membrane. Externally added LPC is rapidly acylated by a membrane-bound enzyme that shows the highest specific activity in the purified plasma membrane. The fatty acid incorporated into the sn-2 position of LPC is preferentially linoleic (18:2), which is the most abundant acyl component in the PC species of Eschscholzia cells, but a minor component of the pool of free fatty acids. The fatty acid at the sn-1 position of LPC is less important for substrate specificity. The capacity of LPC acylation by intact cells or isolated plasma membranes by far exceeds the rate of LPC generation by activated phospholipase A(2) and is not limited by the availability of acyl donors. Metabolites other than phosphatidylcholine (PC) were not significantly produced from labeled LPC within 20 min, indicating that lysophospholipases are not significantly contributing to the short-time metabolism of LPC. It is concluded that reacylation to PC is the dominating process in the detoxication of LPC and ensures the transient character of its steady state concentrations, even at maximum phospholipase A(2) activities.     

Treatment of the enhanced intestinal uptake of glucose in diabetic rats with a polyunsaturated fatty acid diet

Intestinal absorption of most nutrients is enhanced in diabetic rats. We wished to test the hypothesis that manipulation of dietary fatty acids will modify enhanced uptake of glucose in rats with established streptozotocin-diabetes. Chow-fed control rats or animals with one week of streptozotocin-diabetes were continued on chow or were fed ad libitum for three weeks with semisynthetic isocaloric diets containing a high content of either essential polyunsaturated or non-essential saturated fatty acids. The jejunal and ileal in vitro uptake of varying concentrations of glucose was much higher in diabetic than control rats fed chow or the saturated fatty acid diet. In contrast, the enhanced uptake of this sugar was reduced or normalized in diabetic rats fed the polyunsaturated fatty acid diet. Feeding the polyunsaturated fatty acid diet was associated with increased brush-border membrane activity of alkaline phosphatase in diabetic jejunum and ileum, but neither the saturated fatty acid diet nor the polyunsaturated fatty acid diet altered brush-border membrane cholesterol or phospholipids in control or in diabetic rats. Mucosal surface area was similar in diabetic rats fed the saturated fatty acid diet or the polyunsaturated fatty acid diet. Thus, (1) feeding the polyunsaturated fatty acid diet diminishes the enhanced jejunal and ileal uptake of glucose in diabetic rats, and (2) the influence of the polyunsaturated fatty acid diet on uptake in diabetic rats was not explained by alterations in intestinal morphology or brush-border membrane content of cholesterol or phospholipids. This study suggests that manipulation of dietary lipids may play a role in the normalization of the enhanced intestinal glucose uptake in rats with established diabetes.     

Enhanced prostaglandin synthesis as a mechanism for inhibition of melanoma cell growth by ascorbic acid

Both ascorbic acid and the 1-series prostaglandins have been reported to be important regulators of cell growth and since ascorbic acid also increases the synthesis of the 1-series prostaglandins, it is possible that the effects of ascorbic acid on cell growth might be mediated by changes in 1-series prostaglandin synthesis induced by ascorbic acid. This study attempted to examine this possible relationship. The effects of ascorbic acid, prostaglandin E1 and the essential fatty acid precursors of the prostaglandins, linoleic acid and gamma-linolenic acid on the in vitro growth of transformed BL6 murine melanoma cells and untransformed monkey kidney (LLCMK) cells was determined. The effects of ascorbic acid addition on the growth inhibitory effect of the essential fatty acids and on the activity of delta-6-desaturase, a key enzyme in 1-series prostaglandin synthesis were also examined. Addition of ascorbic acid, prostaglandin E1 and both essential fatty acids was found to reduce BL6 growth while PGE1 and to a lesser extent the essential fatty acids reduced LLCMK cell growth. The growth inhibitory effect of the essential fatty acids was enhanced by ascorbic acid which was also found to stimulate delta-6-desaturase activity in BL6 cells. The growth inhibitory effect of ascorbic acid on BL6 cells may thus be mediated by changes in prostaglandin synthesis through an association with the metabolism of the essential fatty acid precursors of the prostaglandins.     

Arachidonic acid inhibits glycine transport in cultured glial cells.

The effects of arachidonic acid on glycine uptake, exchange and efflux in C6 glioma cells were investigated. Arachidonic acid produced a dose-dependent inhibition of high-affinity glycine uptake. This effect was not due to a simple detergent-like action on membranes, as the inhibition of glycine transport was most pronounced with cis-unsaturated long-chain fatty acids, whereas saturated and trans-unsaturated fatty acids had relatively little or no effect. Endogenous unsaturated non-esterified fatty acids may exert a similar inhibitory effect on the transport of glycine. The mechanism for this inhibitory effect has been examined in a plasma membrane vesicle preparation derived from C6 cells, which avoids metabolic or compartmentation interferences. The results suggest that part of the selective inhibition of glycine transport by arachidonic acid could be due to the effects of the arachidonic acid on the lipid domain surrounding the carrier.     

Nonesterified fatty acids inhibit iron-dependent lipid peroxidation

The effect of various fatty acids on lipid peroxidation of liver microsomes induced by different methods in vitro was studied using oxygen uptake and malonaldehyde (MDA) production. It was observed that fatty acids with a single double bond are effective inhibitors of peroxidation. Stereo and positional isomers of oleic acid were equally effective as oleic acid. There was an absolute requirement for a free carboxyl group, since methyl esters of fatty acids and long-chain saturated and unsaturated hydrocarbons could not inhibit peroxidation. Saturated fatty acids with a chain length of 12-16 carbon atoms showed inhibition, whereas more than 18 carbon atoms reduced the inhibitory capacity. Fatty acids of lower chain length such as capric and caprylic acids did not show inhibition. Fatty acid inhibition was partially reversed by increasing the concentration of iron in the system. Peroxidation induced by methods which were independent of iron was not inhibited by fatty acids. It was observed that intestinal microsomes which were resistant to peroxidation due to the presence of nonesterified fatty acids in their membrane lipids were able to peroxidise by methods which do not require iron. These results suggest that certain fatty acids inhibit peroxidation by chelating available free iron. In addition, they may also be involved in competing with the esterified fatty acids in the membrane lipids which are the substrates for peroxidation.     

Expression of Madin-Darby canine kidney cell Na(+)-and Cl(-)-dependent taurine transporter in Xenopus laevis oocytes.

Expression of a Madin-Darby canine kidney (MDCK) cell taurine transporter was examined in Xenopus oocytes that had been injected with poly(A)+ RNA extracted from MDCK cells. Compared with water-injected oocytes, injection of total poly(A)+ RNA resulted in an increase in Na(+)-dependent taurine uptake which was directly related to the amount of RNA injected. The magnitude of expression in poly(A)+ RNA-injected oocytes was 5-10-fold higher than that of water-injected oocytes. Since the Vmax of taurine uptake in MDCK cells is increased by culture in hypertonic medium, we compared oocyte taurine uptake after injection with poly(A)+ RNA from MDCK cells cultured in hypertonic medium with uptake in oocytes injected with poly(A)+ RNA from hypertonic cells elicited twice the taurine uptake elicited by poly(A)+ RNA from isotonic cells. The transporter expressed in oocytes was like that in MDCK cells: it was completely dependent on external sodium and was also anion dependent (Cl- greater than or equal to Br- greater than SCN- much greater than gluconate-). Other beta-amino acids, beta-alanine and hypotaurine, inhibited taurine uptake, but L-alanine and 2-(methylamino) isobutyric acid did not. The apparent Km of the transporter was 7.0 microM. After size fractionation on a sucrose density gradient, poly(A)+ RNA encoding for the MDCK taurine transporter was found in the fraction whose average size was 4.4 kilobases.     

Lysophosphatidylcholine Induces Taurine Release from HeLa Cells

The putative role of lysophospholipids in activation and regulation of the volume-sensitive taurine efflux was investigated in HeLa cells using tracer technique. Lysophosphatidylcholine (LPC, 10 μm) with oleic acid increased taurine efflux during hypotonic and isotonic conditions. Substituting palmitic or stearic acid for oleic acid enhanced taurine release during isotonic conditions, whereas ethanolamine, serine or inositol containing lysophospholipids were ineffective. High concentrations of LPC (25 μm) induced Ca²⁺ influx, loss of adenosine nucleotides, taurine and the Ca²⁺-sensitive probe Fura-2, and thus reflected a general breakdown of the membrane permeability barrier. Low concentrations of LPC (5–10 μm) solely induced taurine efflux. The LPC-induced taurine release was unaffected by anion channel blockers (DIDS, MK196) and the 5-lipoxygenase inhibitor ETH 615-139, which all blocked the volume sensitive taurine efflux. Furthermore, LPC-induced taurine release was reduced by antioxidants (NDGA, vitamin E) and the protein tyrosine kinase inhibitor genistein. The swelling-induced taurine efflux was in the absence of LPC unaffected by vitamin E, blocked by genistein, and increased by H₂O₂ and the protein tyrosine phosphatase inhibitor vanadate. It is suggested that low concentrations of LPC permeabilizes the plasma membrane in a Ca²⁺-independent process that involves generation of reactive oxygen species and tyrosine phosphorylation, and that LPC is not a second messenger in activation of the volume sensitive taurine efflux in HeLa cells. Received: 17 December 1999/Revised: 13 April 2000     

The effect of endogenous essential and nonessential fatty acids on the uptake and subsequent agonist-induced release of arachidonate

We have demonstrated that the uptake and agonist-induced release of a pulse of arachidonate are influenced by the size and composition of preexisting endogenous fatty acid pools. EFD-1 cells, an essential fatty acid-deficient mouse fibrosarcoma cell line, were incubated with radiolabeled (14C or 3H] arachidonate, linoleate, eicosapentaenoate (EPA), palmitate, or oleate in concentrations of 0-33 microM for 24 h. After 24 h, the cells were pulsed with 0.67 microM radiolabeled (3H or 14C, opposite first label) arachidonate for 15 min and then stimulated with 10 microM bradykinin for 4 min. Because EFD-1 cells contain no endogenous essential fatty acids, we were able to create essential fatty acid-repleted cells for which the specific activity of the newly constructed endogenous essential fatty acid pool was known. Loading the endogenous pool with the essential fatty acids arachidonate, eicosapentaenoate, or linoleate (15-20 nmol of fatty acid incorporated/10(6) cells) decreased the uptake of a pulse of arachidonate from 200 to 100 pmol/10(6) cells but had no effect on palmitate uptake. The percent of arachidonate incorporated during the pulse which was released upon agonist stimulation increased 2-fold (4-8%) as the endogenous pool of essential fatty acids was increased from 0 to 15-20 nmol/10(6) cells. This 8% release was at least 3-fold greater than the percent release from the various endogenous essential fatty acid pools. In contrast, loading the endogenous pool with the nonessential fatty acids oleate or palmitate to more than 2-3 times their preexisting cellular level had no effect on the uptake of an arachidonate pulse. Like the essential fatty acids, increasing endogenous oleate increased (by 2-fold) the percent release of arachidonate incorporated during the pulse, whereas endogenous palmitate had no effect on subsequent agonist-induced release from this arachidonate pool. These studies show that preexisting pools of essential and nonessential fatty acids exert different effects on the uptake and subsequent releasability of a pulse of arachidonate.     

β-Glucan extracts inhibit the in vitro intestinal uptake of long-chain fatty acids and cholesterol and down-regulate genes involved in lipogenesis and lipid transport in rats

BackgroundDietary fiber reduces the intestinal absorption of nutrients and the blood concentrations of cholesterol and triglycerides.AimWe wished to test the hypothesis that high-viscosity (HV) and low-viscosity preparations of barley and oat β-glucan modify the expression of selected genes of lipid-binding proteins in the intestinal mucosa and reduce the intestinal in vitro uptake of lipids.MethodsFive different β-glucan extracts were separately added to test solutions at concentrations of 0.1–0.5% (wt/wt), and the in vitro intestinal uptake of lipids into the intestine of rats was assessed. An intestinal cell line was used to determine the effect of β-glucan extracts on the expression of intestinal genes involved in lipid metabolism and fatty acid transport.ResultsAll extracts reduced the uptake of 18:2 when the effective resistance of the unstirred water layer was high. When the unstirred layer resistance was low, the HV oat β-glucan extract reduced jejunal 18:2 uptake, while most extracts reduced ileal 18:2 uptake. Ileal 18:0 uptake was reduced by the HV barley extract, while both jejunal and ileal cholesterol uptakes were reduced by the medium-purity HV barley extract. The inhibitory effect of HV barley β-glucan on 18:0 and 18:2 uptake was more pronounced at higher fatty acid concentrations. The expression of genes involved in fatty acid synthesis and cholesterol metabolism was down-regulated with the HV β-glucan extracts. β-Glucan extracts also reduced intestinal fatty-acid-binding protein and fatty acid transport protein 4 mRNA.ConclusionsThe reduced intestinal fatty acid uptake observed with β-glucan is associated with inhibition of genes regulating intestinal uptake and synthesis of lipids. The inhibitory effect of β-glucan on intestinal lipid uptake raises the possibility of their selective use to reduce their intestinal absorption.