Mechanism of oleoylethanolamide on fatty acid uptake in small intestine after food intake and body weight reduction

The increase in the prevalence of human obesity highlights the need to identify molecular and cellular mechanisms involved in control of feeding and energy balance. Oleoylethanolamide (OEA), an endogenous lipid produced primarily in the small intestine, has been identified to play an important role in the regulation of animal food intake and body weight. Previous studies indicated that OEA activates peroxisome proliferator-activated receptor-alpha, which is required to mediate the effects of appetite suppression, reduces blood lipid levels, and enhances peripheral fatty acid catabolism. However, the effect of OEA on enterocyte function is unclear. In this study, we have examined the effect of OEA on intestinal fatty acid uptake and FAT/CD36 expression in vivo and in vitro. We intraperitoneally administered OEA to rats and examined FAT/CD36 mRNA level and fatty acid uptake in enterocytes isolated from the proximal small intestine, as well as in adipocytes. Our results indicate that OEA treatment significantly increased FAT/CD36 mRNA expression in intestinal mucosa and isolated jejunal enterocytes. In addition, we also found that OEA treatment significantly increases fatty acid uptake in isolated enterocytes in vitro. These results suggest that in addition to appetite regulation, OEA may regulate body weight by altered peripheral lipid metabolism, including increased lipolysis in adipocytes and enhanced fatty acid uptake in enterocytes, both in conjunction with increased expression of FAT/CD36. This study may have important implications in understanding the mechanism of OEA in the regulation of fatty acid absorption in human physiological and pathophysiological conditions.     

Lymphatic absorption of fatty acids and cholesterol in the neonatal rat

High-fat diets are essential in suckling animals to ensure adequate calories for postnatal growth, but their lymphatic transport of dietary lipids has not been characterized. We established a lymph fistula model in suckling rats to quantify intestinal uptake and lymphatic transport of dietary lipids and analyzed lipoprotein fractions. Suckling 19-day-old Sprague-Dawley rats had their mesenteric lymph ducts cannulated and gastroduodenal tubes inserted. After overnight recovery, [(3)H]triolein and [(14)C]cholesterol were infused for 6 h. Of the total dose, only 38% of triolein and 24% of cholesterol were transported in the lymph of suckling rats. Analyses of residual luminal contents and intestinal mucosal homogenate showed neither reduced absorption nor delayed mucosal processing of ingested lipids to be the cause. Thin-layer chromatographic analysis of radioactive mucosal lipids, however, showed a predominance of free fatty acids (60%) and free cholesterol (67%), implying impaired esterification capacity in these animals. We speculate that this reduced esterification allows for portal transport or direct enterocyte metabolism of dietary lipids.     

The uptake of oleic acid by rat small intestine: a comparison of methodologies

The interaction between long-chain and medium-chain lipids during intestinal absorption was examined using several model systems. A decrease in steady-state triolein (LCT) output in thoracic duct lymph after addition of trioctanoin (MCT) to the duodenal infusion confirmed previous studies in unanesthetized rats which demonstrated inhibition of steady-state LCT uptake from the small intestinal lumen by MCT. In slices of everted rat jejunum octanoic acid reduced incorporation into triglyceride and initial uptake of (14)C-labeled oleic acid from micellar solutions. Inhibition of uptake did not occur at 0 degrees C, when triglyceride synthesis was blocked. Incubation of slices at low pH (5.8) or in the presence of dimethyl sulfoxide also reduced uptake of oleic acid and its incorporation into triglyceride. However, when everted sacs of jejunum were similarly incubated, octanoate, dimethyl sulfoxide, or low pH caused no inhibition of oleic acid uptake or esterification. The results indicate that the significance of kinetic data describing intestinal fatty acid absorption which were obtained from experiments conducted in vitro is highly questionable, and that suitable models for in vivo uptake kinetics have yet to be developed. However, analysis of the in vitro kinetic data suggests that the intestinal mucosal membrane does not function as a simple lipid interface with respect to fatty acid absorption.     

Microanatomy of the intestinal lymphatic system

The intestinal lymphatic system comprises two noncommunicating lymphatic networks: one containing the lacteals draining the villi and the connecting submucosal lymphatic network and one containing the lymphatics that drain the intestine muscular layer. These systems deliver lymph into a common network of collecting lymphatics originating near the mesenteric border. The intestinal lymphatic system serves vital functions in the regulation of tissue fluid homeostasis, immune surveillance, and the transport of nutrients; conversely, this system is affected by, and directly contributes to, disease processes within the intestine. Recent discoveries of specific lymphatic markers, factors promoting lymphangiogenesis, and factors selectively affecting the development of intestinal lymphatics, hold promise for unlocking the role of lymphatics in the pathogenesis of diseases affecting the intestine and for intestinal lymphatic selective therapies. Vital to progress in understanding how the intestinal lymphatic system functions is the integration of recent advances identifying molecular pathways for lymphatic growth and remodeling with advanced imaging modalities to observe lymphatic function and dysfunction in vivo.     

Cytarabine induces cachexia with lipid malabsorption via zippering the junctions of lacteal in murine small intestine

Chemotherapy-induced cachexia causes severe metabolic abnormalities independently of cancer and reduces the therapeutic efficacy of chemotherapy. The underlying mechanism of chemotherapy-induced cachexia remains unclear. Here we investigated the cytarabine (CYT)-induced alteration in energy balance and its underlying mechanisms in mice. We compared energy balance-associated parameters among the three groups of mice: CON, CYT, and PF (pair-fed mice with the CYT group) that were intravenously administered vehicle or CYT. Weight gain, fat mass, skeletal muscle mass, grip strength, and nocturnal energy expenditure were significantly lowered in the CYT group than in the CON and PF groups. The CYT group demonstrated less energy intake than the CON group and higher respiratory quotient than the PF group, indicating that CYT induced cachexia independently from the anorexia-induced weight loss. Serum triglyceride was significantly lower in the CYT group than in the CON group, whereas the intestinal mucosal triglyceride levels and the lipid content within the small intestine enterocyte were higher after lipid loading in the CYT group than in the CON and PF groups, suggesting that CYT inhibited lipid uptake in the intestine. This was not associated with obvious intestinal damage. The CYT group showed increased zipper-like junctions of lymphatic endothelial vessel in duodenal villi compared to that in the CON and CYT groups, suggesting their imperative role in the CYT-induced inhibition of lipid uptake. CYT worsens cachexia independently of anorexia by inhibiting the intestinal lipid uptake, via the increased zipper-like junctions of lymphatic endothelial vessel.     

Intestinal absorption and lymphatic transport of cholesterol in the rat: influence of the fatty acid chain length of the carrier triglyceride

This paper deals with the effect of the fatty acid chain length of dietary triglyceride on the intestinal uptake and lymphatic transport of exogenous and endogenous cholesterol in the rat. This question seemed of interest as the chain length of the monoglyceride and fatty acids formed in the intestinal lumen from the triglyceride fed could be expected to affect the concentration of cholesterol in the micellar or isotropic phase of intestinal content. Feeding rats medium- or short-chain triglycerides (C(12) to C(2)) did not affect the lymphatic transport of endogenous cholesterol from the intestine compared to the fasting state. The extent of lymphatic transport of cholesterol added to these fats increased proportionally with chain length (C(6)-C(18)) of the component fatty acids. The uptake of exogenous cholesterol into the intestinal wall was similarly related to the chain length of the carrier triglyceride, with the exception of triacetin, which gave a much higher intestinal uptake than lymphatic transport. When cholesterol was fed in octadecane, negligible amounts only were transported to the thoracic duct lymph. This again indicates the importance of the polar split products of dietary fat for cholesterol absorption.     

A model for mechanics of primary lymphatic valves

Recent experimental evidence indicates that lymphatics have two valve systems, a set of primary valves in the wall of the endothelial cells of initial lymphatics and a secondary valve system in the lumen of the lymphatics. While the intralymphatic secondary valves are well described, no analysis of the primary valves is available. We propose a model for primary lymphatics valves at the junctions between lymphatic endothelial cells. The model consists of two overlapping endothelial extensions at a cell junction in the initial lymphatics. One cell extension is firmly attached to the adjacent connective tissue while the other cell extension is not attached to the interstitial collagen. It is free to bend into the lumen of the lymphatic when the lymphatic pressure falls below the adjacent interstitial fluid pressure. Thereby the cell junction opens a gap permitting entry of interstitial fluid into the lymphatic lumen. When the lymphatic fluid pressure rises above the adjacent interstitial fluid pressure, the endothelial extensions contact each other and the junction is closed preventing fluid reflow into the interstitial space. The model illustrates the mechanics of valve action and provides the first time a rational analysis of the mechanisms underlying fluid collection in the initial lymphatics and lymph transport in the microcirculation.     

Mouse LYVE-1 is an endocytic receptor for hyaluronan in lymphatic endothelium

The glycosaminoglycan hyaluronan is a key substrate for cell migration in tissues during inflammation, wound healing, and neoplasia. Unlike other matrix components, hyaluronan (HA) is turned over rapidly, yet most degradation occurs not locally but within distant lymph nodes, through mechanisms that are not yet understood. While it is not clear which receptors are involved in binding and uptake of hyaluronan within the lymphatics, one likely candidate is the lymphatic endothelial hyaluronan receptor LYVE-1 recently described in our laboratory (Banerji, S., Ni, J., Wang, S., Clasper, S., Su, J., Tammi, R., Jones, M., and Jackson, D.G. (1999) J. Cell Biol. 144, 789-801). Here we present evidence that LYVE-1 is involved in the uptake of hyaluronan by lymphatic endothelial cells using a new murine LYVE-1 orthologue identified from the EST data base. We show that mouse LYVE-1 both binds and internalizes hyaluronan in transfected 293T fibroblasts in vitro and demonstrate using immunoelectron microscopy that it is distributed equally among the luminal and abluminal surfaces of lymphatic vessels in vivo. In addition, we show by means of specific antisera that expression of mouse LYVE-1 remains restricted to the lymphatics in homozygous knockout mice lacking a functional gene for CD44, the closest homologue of LYVE-1 and the only other Link superfamily HA receptor known to date. Together these results suggest a role for LYVE-1 in the transport of HA from tissue to lymph and imply that further novel hyaluronan receptors must exist that can compensate for the loss of CD44 function.     

Contractile activity of lymphatic vessels is altered in the TNBS model of guinea pig ileitis

The ability of the lymphatic system to actively remove fluid from the interstitium is critical to the resolution of edema. The response of the lymphatics to inflammatory situations is poorly studied, so we examined mesenteric lymphatic contractile activity in the 2,4,6-trinitrobenzenesulfonic acid (TNBS) model of guinea pig ileitis, a well-accepted animal model of intestinal inflammation, by videomicroscopy in vivo and in vitro 1, 3, and 6 days after induction of ileitis. Lymphatic function (diameter, constriction frequency, amplitude of constrictions, and calculated stroke volume and lymph flow rate) of isolated vessels from TNBS-treated guinea pigs were impaired compared with sham-treated controls. The dysfunction was well correlated with the degree of inflammation, with differences reaching significance (P < 0.05) at the highest inflammation-induced damage observed at day 3. In vivo, significantly fewer lymphatics exhibited spontaneous constrictions in TNBS-treated than sham-treated animals. Cyclooxygenase (COX) metabolites were suggested to be involved in this lymphatic dysfunction, since application of nonselective COX inhibitor (10 microM indomethacin) or a combination of COX-1 and COX-2 inhibitors (1 microM SC-560 and 10 microM celecoxib) markedly increased constriction frequency or induced them in lymphatics from TNBS-treated animals in vivo and in vitro. The present results demonstrate that lymphatic contractile function is altered in TNBS-induced ileitis and suggest a role for prostanoids in the lymphatic dysfunction.     

Effect of ethanol on intestinal lipid absorption in the rat

The effect of ethanol infusion on intestinal lipid absorption was studied in rats with a duodenal cannula. Rats were infused with ethanol overnight and ethanol was included in a trioleoylglycerol emulsion infusion given for 3 hr the next day. These rats were compared to control animals infused with glucose (isocalorically). The ethanol-infused rats had a greatly impaired lipid absorptive capacity. The monoacylglycerol and free fatty acid contents in the intestinal lumen in the ethanol-infused rats were 4- and 7-fold greater, respectively, than controls. The inhibition of absorption was not due to an effect of ethanol on lipolytic activity. The lipase content of the ethanol-infused rats was greater than controls and the separate infusion of monoacylglycerol and fatty acids demonstrated impaired absorption of these end products of lipolysis as compared to controls. To observe if these changes were due to an effect of ethanol on the enterocyte brush border membrane, the membrane lipids were analyzed. The phosphatidylcholine, lysophosphatidylcholine, and phosphatidylethanolanine content was reduced but not the neutral lipids, sphingomyelin, or phosphatidylserine. The uptake of fatty acid into intestinal rings was also shown to be impaired by ethanol infusion. Lastly, the specific activity of the neutral lipids remaining in the intestinal lumen after [3H]glycerol-labeled trioleoylglycerol-infusion was similar to controls even though the mass was much greater. It is concluded that ethanol impairs neutral lipid absorption due to an effect on the enterocyte brush border membrane and by increasing the efflux of low specific activity lipid from the enterocyte back out into the intestinal lumen. A potential pathway for this efflux is the recently described increased porosity of the apical junctional complex in response to ethanol infusion.     

The 1991 Borden Award Lecture. Selected aspects of intraluminal and intracellular phases of intestinal fat absorption.

The recognition of chylomicrons as dietary lipid transporters dates back to more than 70 years and marks a milestone in lipoprotein history. Conventionally, three phases constitute the process of absorption of exogenous fat: intraluminal, intestinal, and delivery. The intraluminal phase includes chemical hydrolysis by lipolytic enzymes and the micellar solubilization of lipolytic products by bile acids. The intestinal phase comprises the diffusion of micelles through the unstirred water layer, passive diffusion across the microvillous membrane of the enterocyte, and the formation of lipid-carrying lipoproteins. The delivery phase involves the exocytosis of chylomicrons from the absorptive cells and their subsequent removal by lymphatic structures and the systemic circulation. The precise steps and factors involved in all phases of chylomicron synthesis are not yet known, but both experimental and clinical studies have been helpful. Of the inborn metabolic disorders, the prerequisite function of apolipoprotein (apo B) for the assembly and release of lipoprotein particles stood out. Moreover, evidence emerged that the enterocyte produces apo B-100 in addition to apo B-48. Calcium and essential fatty acid status originates as determinants for triglyceride-rich particle synthesis. Furthermore, the developmental changes and regulatory factors of lipoprotein elaboration represent excellent tools in the study of the intracellular mechanisms of lipid transport.     

The intestine as source of cytotoxic mediators in shock: free fatty acids and degradation of lipid-binding proteins

Shock and multiple organ failure remain primary causes of late-stage morbidity and mortality in victims of trauma. During shock, the intestine is subject to extensive cell death and is the source of inflammatory factors that cause multiorgan failure. We (34) showed previously that ischemic, but not nonischemic, small intestines and pancreatic protease digested homogenates of normal small intestine can generate cytotoxic factors capable of killing naive cells within minutes. Using chloroform/methanol separation of rat small intestine homogenates into lipid fractions and aqueous and sedimented protein fractions and measuring cell death caused by those fractions, we found that the cytotoxic factors are lipid in nature. Recombining the lipid fraction with protein fractions prevented cell death, except when homogenates were protease digested. Using a fluorescent substrate, we found high levels of lipase activity in intestinal homogenates and cytotoxic levels of free fatty acids. Addition of albumin, a lipid binding protein, prevented cell death, unless the albumin was previously digested with protease. Homogenization of intestinal wall in the presence of the lipase inhibitor orlistat prevented cell death after protease digestion. In vivo, orlistat plus the protease inhibitor aprotinin, administered to the intestinal lumen, significantly improved survival time compared with saline in a splanchnic arterial occlusion model of shock. These results indicate that major cytotoxic mediators derived from an intestine under in vitro conditions are free fatty acids. Breakdown of free fatty acid binding proteins by proteases causes release of free fatty acids to act as powerful cytotoxic mediators.     

Release of free fatty acids from Ehrlich ascites tumor cells

Ehrlich ascites tumor cells release free fatty acids (FFA) during in vitro incubation in media that contain albumin. The released FFA are derived by lipolysis from endogenous lipid esters. Addition of glucose to the incubation medium greatly decreases the quantity of fatty acid released by the cells. Cyanide, which inhibits endogenous lipid oxidation but not lipolysis, increases the quantity of fatty acid released to media containing albumin and causes free fatty acid to accumulate in the cells in the absence of exogenous albumin. The release of fatty acid, either preformed or derived by lipolysis during prolonged incubations, occurs under conditions of net fatty acid uptake from the incubation medium. Net release of fatty acid from the cell occurs only when fatty acid-extracted albumin is present in the extracellular medium; extrapolation of the data suggests that net release will not occur under physiological conditions. It is postulated that free fatty acid uptake and release are independent processes, the direction of net fatty acid movement being determined by the relationship between cellular free fatty acid concentration (regulating efflux) and the molar ratio of free fatty acid to albumin in the extracellular medium (regulating uptake).     

Effect of albumin on oleic acid lymphatic absorption in rats

1. The aim of this study was to investigate how fatty acid absorption was affected when exogenous fatty acids were complexed with albumin in absence of bile. Experiments were carried out in vivo, in order to study overall absorption processes. 2. An equimolar mixture of 14C oleic acid, palmitic acid and monopalmitin was infused intraduodenally in bile- and pancreatic juice-diverted rats. 3. Lipids were emulsified with either sodium taurocholate or fatty acids complexed with albumin. 4. Lymphatic lipid output was compared during the 6 hr following infusion of 90 mumol of the radioactive lipid mixture. 5. Lymphatic radioactive lipid recovery was significantly decreased by albumin. 6. Only 17% of the infused radioactivity was recovered in lymph when fatty acids were complexed with albumin against 37% when lipids were emulsified with sodium taurocholate. 7. Unrecovered lymph radioactivity was found at the distal part of intestine. Moreover, albumin significantly decreased lymph flow. 8. We conclude that undigested albumin acted at the luminal level of lipid absorption processes and specifically decreased fatty acid uptake.     

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.     

Fatty acid uptake and metabolism in a human intestinal cell line (Caco-2): comparison of apical and basolateral incubation

Free fatty acids can enter the enterocyte via the apical or basolateral plasma membrane. We have used the Caco-2 intestinal cell line to examine the polarity of free fatty acid uptake and metabolism in the enterocyte. Differentiated Caco-2 cells form polarized monolayers with tight junctions, and express the small intestine-specific enzymes sucrase and alkaline phosphatase. Cells were grown on permeable polycarbonate Transwell filters, thus allowing separate access to the apical and basolateral compartments. Total uptake of [3H]palmitate bound to bovine serum albumin (palmitate-BSA 4:1) was twofold higher (P less than 0.05 or less) at the apical surface than at the basolateral surface. The relative apical and basolateral membrane surface areas of the Caco-2 cells, as measured by partition of the fluorophore trimethylammonium-diphenylhexatriene TMA-DPH), was found to be 1:3. Thus, apical fatty acid uptake was sixfold higher than basolateral uptake per unit surface area. Analysis of metabolites after incubation with submicellar concentrations of [3H]palmitate showed that the triacylglycerol to phospholipid (TG:PL) ratio was higher for fatty acid added to the apical as compared to the basolateral compartment (20% at 60 min, P less than 0.025). Little fatty acid oxidation was observed. Preincubation with albumin-bound palmitate, alone or with monoolein, increased the incorporation of both apical and basolateral free fatty acids into TG. The results suggest that the net uptake of long-chain free fatty acids across the apical plasma membrane is greater than uptake across the basolateral membrane. In addition, a small increase in the TG:PL ratio for apically, compared to basolaterally, added free fatty acids suggests that polarity of metabolism occurs to a limited extent in Caco-2 enterocytes.     

Gut expression and regulation of FAT/CD36: possible role in fatty acid transport in rat enterocytes

Fatty acid translocase (FAT)/CD36 is one of several putative plasma membrane long-chain fatty acid (LCFA) transport proteins; however, its role in intestinal absorption of LCFA is unknown. We hypothesized that FAT/CD36 would be differentially expressed along the longitudinal axis of the gut and during intestinal development, suggesting specificity of function. We found that intestinal mucosal FAT/CD36 mRNA levels varied by anatomic location along the longitudinal gut axis: stomach 45 +/- 7, duodenum 173 +/- 29, jejunum 238 +/- 17, ileum 117 +/- 14, and colon 9 +/- 1% (means +/- SE with 18S mRNA as control). FAT/CD36 protein levels were also higher in proximal compared with distal intestinal mucosa. Mucosal FAT/CD36 mRNA was also regulated during intestinal maturation, with a fourfold increase from neonatal to adult animals. In addition, FAT/CD36 mRNA levels and enterocyte LCFA uptake were rapidly downregulated by intraduodenal oleate infusion. These findings suggest that FAT/CD36 plays a role in the uptake of LCFA by small intestinal enterocytes. This may have important implications in understanding fatty acid absorption in human physiological and pathophysiological conditions.     

Evidence for a second valve system in lymphatics: endothelial microvalves.

The mechanism for interstitial fluid uptake into the lymphatics remains speculative and unresolved. A system of intralymphatic valves exists that prevents reflow along the length of the lymphatic channels. However, these valves are not sufficient to provide unidirectional flow at the level of the initial lymphatics. We investigate here the hypothesis that initial lymphatics have a second, separate valve system that permits fluid to enter from the interstitium into the initial lymph channels but prevents escape back out into the tissue. The transport of fluorescent microspheres (0.31 microm) across endothelium of initial lymphatics in rat cremaster muscle was investigated with micropipette manipulation techniques. The results indicate that microspheres can readily pass from the interstitium across the endothelium into the lumen of the initial lymphatics. Once inside the lymphatic lumen, the microspheres cannot be forced out of the lumen even after elevation of the lymphatic pressure by outflow obstruction. Reaspiration of the microspheres inside the lymphatic lumen with a micropipette is blocked by the lymphatic endothelium. This blockade exists whether the aspiration is carried out at the microsphere entry site or anywhere along the initial lymphatics. Nevertheless, puncture of the initial lymphatic endothelium with the micropipette leads to rapid aspiration of intralymphatic microspheres. Investigation of lymphatic endothelial sections fixed during lymph pumping shows open interendothelial junctions not found in resting initial lymphatics. These results suggest that initial lymphatics have a (primary) valve system at the level of the endothelium. In conjunction with the classical (secondary) intralymphatic valves, the primary valves provide the mechanism that facilitates the unidirectional flow during periodic compression and expansion of initial lymphatics.     

Dextran sodium sulfate (DSS) induces colitis in mice by forming nano-lipocomplexes with medium-chain-length fatty acids in the colon

Inflammatory bowel diseases (IBDs), primarily ulcerative colitis and Crohn's disease, are inflammatory disorders caused by multiple factors. Research on IBD has often used the dextran sodium sulfate (DSS)-induced colitis mouse model. DSS induces in vivo but not in vitro intestinal inflammation. In addition, no DSS-associated molecule (free glucose, sodium sulfate solution, free dextran) induces in vitro or in vivo intestinal inflammation. We find that DSS but not dextran associated molecules established linkages with medium-chain-length fatty acids (MCFAs), such as dodecanoate, that are present in the colonic lumen. DSS complexed to MCFAs forms nanometer-sized vesicles ~200 nm in diameter that can fuse with colonocyte membranes. The arrival of nanometer-sized DSS/MCFA vesicles in the cytoplasm may activate intestinal inflammatory signaling pathways. We also show that the inflammatory activity of DSS is mediated by the dextran moieties. The deleterious effect of DSS is localized principally in the distal colon, therefore it will be important to chemically modify DSS to develop materials beneficial to the colon without affecting colon-targeting specificity.     

Intestinal lipid absorption is not affected in CD36 deficient mice

Increasing evidence has implicated the membrane protein CD36 (or fatty acid translocase, FAT) to be involved in high affinity fatty acid uptake. CD36 is expressed in tissues active in fatty acid metabolism, like adipose tissue and skeletal and cardiac muscle, but also in intestine. CD36 is localized in the intestine mainly in the jejunal villi, where it is confined to enterocyte apical membrane.The aim was to determine the role of CD36 in intestinal lipid absorption. Lipid absorption was determined by administering ³H-labeled triolein and ¹⁴C-labeled palmitic acid as an olive oil bolus by intragastric gavage and determine appearance of ³H and ¹⁴C label in plasma, after blocking lipolysis by i.v. injections of Triton WR 1339. Surprisingly, no differences in plasma appearance of ³H-label or ¹⁴C-label were observed in CD36^–/– mice compared to wild type controls. These results suggest that CD36 does not play a role in intestinal lipid absorption after an acute lipid load.