Plasma essential fatty acid on hospital admission is a marker of COVID-19 disease severity.

It is important for allocation of resources to predict those COVID patients at high risk of dying or organ failure. Early signals to initiate cellular events of host immunity can be derived from essential fatty acid metabolites preceding the cascade of proinflammatory signals. Much research has focused on understanding later proinflammatory responses. We assessed if remodelling of plasma phospholipid content of essential fatty acids by the COVID-19 virus provides early markers for potential death and disease severity. Here we show that, at hospital admission, COVID-19 infected subjects who survive exhibit higher proportions of C20:4n-6 in plasma phospholipids concurrent with marked proinflammatory cytokine elevation in plasma compared to healthy subjects. In contrast, more than half of subjects who die of this virus exhibit very low C18:2n-6 and C20:4n-6 content in plasma phospholipids on hospital admission compared with healthy control subjects. Moreover, in these subjects who die, the low level of primary inflammatory signals indicates limited or aberrant stimulation of host immunity. We conclude that COVID-19 infection results in early fundamental remodelling of essential fatty acid metabolism. In subjects with high mortality, it appears that plasma n-6 fatty acid content is too low to stimulate cellular events of host immunity.

Glial control of sphingolipid levels sculpts diurnal remodeling in a circadian circuit.

Structural plasticity in the brain often necessitates dramatic remodeling of neuronal processes, with attendant reorganization of the cytoskeleton and membranes. Although cytoskeletal restructuring has been studied extensively, how lipids might orchestrate structural plasticity remains unclear. We show that specific glial cells in Drosophila produce glucocerebrosidase (GBA) to locally catabolize sphingolipids. Sphingolipid accumulation drives lysosomal dysfunction, causing gba1b mutants to harbor protein aggregates that cycle across circadian time and are regulated by neural activity, the circadian clock, and sleep. Although the vast majority of membrane lipids are stable across the day, a specific subset that is highly enriched in sphingolipids cycles daily in a gba1b-dependent fashion. Remarkably, both sphingolipid biosynthesis and degradation are required for the diurnal remodeling of circadian clock neurites, which grow and shrink across the day. Thus, dynamic sphingolipid regulation by glia enables diurnal circuit remodeling and proper circadian behavior.

Transcriptional Feedback Links Lipid Synthesis to Synaptic Vesicle Pools in Drosophila Photoreceptors.

Neurons can maintain stable synaptic connections across adult life. However, the signals that regulate expression of synaptic proteins in the mature brain are incompletely understood. Here, we describe a transcriptional feedback loop between the biosynthesis and repertoire of specific phospholipids and the synaptic vesicle pool in adult Drosophila photoreceptors. Mutations that disrupt biosynthesis of a subset of phospholipids cause degeneration of the axon terminal and loss of synaptic vesicles. Although degeneration of the axon terminal is dependent on neural activity, activation of sterol regulatory element binding protein (SREBP) is both necessary and sufficient to cause synaptic vesicle loss. Our studies demonstrate that SREBP regulates synaptic vesicle levels by interacting with tetraspanins, critical organizers of membranous organelles. SREBP is an evolutionarily conserved regulator of lipid biosynthesis in non-neuronal cells; our studies reveal a surprising role for this feedback loop in maintaining synaptic vesicle pools in the adult brain.

Prevalence of giardiasis in children attending semi-urban daycare centres in Guatemala and comparison of 3 giardia detection tests.

Giardia intestinalis is an intestinal parasite widely prevalent in children attending daycare centres worldwide and has been associated with undernutrition. Stool samples from 48 Guatemalan children (aged 1.5-7 years) attending participating daycare centres were analyzed over five weeks for presence of Giardia intestinalis using light microscopy, ELISA, and rapid dipstick test. Giardia prevalence rates were 43.7% at Week 0 and 44.7% at Week 4, based on ELISA. Intensity, but not prevalence, of infection showed a trend toward decreased weight-for-age (1-tailed p = 0.08). We believe that ELISA analysis of stool samples may be further adapted for measuring the intensity of infection in humans.

Cancer cachexia in the age of obesity: skeletal muscle depletion is a powerful prognostic factor, independent of body mass index.

PURPOSE: Emerging evidence suggests muscle depletion predicts survival of patients with cancer. PATIENTS AND METHODS: At a cancer center in Alberta, Canada, consecutive patients with cancer (lung or GI; N = 1,473) were assessed at presentation for weight loss history, lumbar skeletal muscle index, and mean muscle attenuation (Hounsfield units) by computed tomography (CT). Univariate and multivariate analyses were conducted. Concordance (c) statistics were used to test predictive accuracy of survival models. RESULTS: Body mass index (BMI) distribution was 17% obese, 35% overweight, 36% normal weight, and 12% underweight. Patients in all BMI categories varied widely in weight loss, muscle index, and muscle attenuation. Thresholds defining associations between these three variables and survival were determined using optimal stratification. High weight loss, low muscle index, and low muscle attenuation were independently prognostic of survival. A survival model containing conventional covariates (cancer diagnosis, stage, age, performance status) gave a c statistic of 0.73 (95% CI, 0.67 to 0.79), whereas a model ignoring conventional variables and including only BMI, weight loss, muscle index, and muscle attenuation gave a c statistic of 0.92 (95% CI, 0.88 to 0.95; P < .001). Patients who possessed all three of these poor prognostic variables survived 8.4 months (95% CI, 6.5 to 10.3), regardless of whether they presented as obese, overweight, normal weight, or underweight, in contrast to patients who had none of these features, who survived 28.4 months (95% CI, 24.2 to 32.6; P < .001). CONCLUSION: CT images reveal otherwise occult muscle depletion. Patients with cancer who are cachexic by the conventional criterion (involuntary weight loss) and by two additional criteria (muscle depletion and low muscle attenuation) share a poor prognosis, regardless of overall body weight.

A fishy conclusion regarding n-3 fatty acid supplementation in cancer patients.

Clinical studies are emerging to support providing long chain n-3 fatty acids, found in fish oils, to prevent muscle loss, minimize side effects and improve chemotherapy response in patients with cancer. However, a recent report using experimental models made the concluding statement "..., the use of [fish oil] products during chemotherapy treatment should be avoided". This recommendation is not in line with current understanding of human nutrient requirements and needs to be carefully weighed against evidence supporting fish oil supplementation. The potential clinical detriment of consuming fish oil when undergoing platinum based therapies claimed by Roodhart et al. is not taken within the context of the collective work citing beneficial effects of fish oil in experimental models as well as in humans. Platinum-based therapies are standard of care for lung cancer in many regions of the world with no evidence that they are more or less effective than in countries where oily fish intake is minimal. Overall, the human nutrition recommendations made in the discussion of Roodhart et al. are not supported by the experimental evidence provided in the paper nor within the context of other work in this area.

Aberrations in plasma phospholipid fatty acids in lung cancer patients.

Abnormalities in lipid metabolism have been frequently observed in cancer and are associated with a poor prognosis. However, a detailed, longitudinal characterization of fatty acid status is lacking. This study aimed to assess plasma phospholipid fatty acids before chemotherapy, immediately after and 1 month following chemotherapy in a group of 50 patients newly diagnosed with lung cancer and explore factors which may contribute to aberrations in fatty acids. Their mean ± SD characteristics: age 64 ± 8.5 years, 75% advanced stage disease, body mass index 27.0 ± 5.4 kg/m², 6 month weight loss -4.6 ± 6.1%. Compared to patients with early stage disease, patients with advanced disease had abnormal fatty acid profiles including significantly lower (P < 0.05) amounts of total phospholipid fatty acids, saturated, and polyunsaturated fatty acids (linoleic, arachidonic, eicosapentaenoic and docosahexaenoic). Longitudinal analysis revealed that patients with advanced disease who completed chemotherapy had stable fatty acid levels and continued to maintain levels 1 month following completion of chemotherapy. Comparatively, patients who did not complete chemotherapy due to toxicity or disease progression had progressive loss of total phospholipid fatty acids, stearic, linoleic and n-6 fatty acids and a trend towards lower docosahexaenoic, arachidonic, palmitic, n-3 and saturated fatty acids. These results suggest that loss of fatty acids is prevalent, progressive and potentially influenced by advanced disease and chemotherapy treatment.

Effect of docosahexaenoic acid supplementation on the macular function of patients with Best vitelliform macular dystrophy: randomized clinical trial.

OBJECTIVE: Best disease is a slowly progressive macular dystrophy that typically has an onset in early childhood. Multiple lines of evidence suggest that dietary docosahexaenoic acid (DHA) protects against the development of macular degeneration. Our trial tested the effect of an oral supplement of DHA on visual function in patients with Best disease. DESIGN: Double-masked, randomized, placebo-controlled, crossover clinical trial. PARTICIPANTS: Eight patients with Best disease. METHODS: Patients were given either an oral supplement of DHA (20 mg/kg daily) or placebo. Primary outcome measures were the multifocal electroretinogram (mfERG) and electro-oculogram (EOG). Plasma DHA was tracked along with visual acuity (Early Treatment Diabetic Retinopathy Study chart), VF-14 scores, and Humphrey visual fields. RESULTS: All 8 patients had increased plasma DHA levels (2-3 fold) during periods of DHA supplementation compared with periods without supplementation. Differences in visual acuity, VF-14 scores, and EOG Arden ratios during periods with and without DHA supplementation were all statistically insignificant. A positive correlation was found between the plasma concentration of DHA and mfERG amplitudes, but amplitude changes during the treatment periods were not significant. A carryover effect of DHA supplementation was a confounding error. CONCLUSIONS: Our pilot trial of DHA supplementation in 8 patients with Best disease did not demonstrate an improvement in macular function. An expanded trial would be needed to examine the full effects of DHA supplementation on visual function in Best disease.

Effect of feeding a formula supplemented with long-chain polyunsaturated fatty acids for 14 weeks improves the ex vivo response to a mitogen and reduces the response to a soy protein in infants at low risk for allergy.

BACKGROUND AND OBJECTIVE: Feeding long-chain polyunsaturated fatty acids (LCP) influences immunity in adults; however, less is known about their effect during development. The aim of the study was to determine the effect of feeding LCP on immunity in healthy infants during the first 4 months of life. PATIENTS AND METHODS: Formula-fed infants were randomized at

The effect of a controlled manipulation of maternal dietary fat intake on medium and long chain fatty acids in human breast milk in Saskatoon, Canada.

BACKGROUND: Few studies in recent years have demonstrated the effect of maternal diet on fatty acid composition of human milk. METHODS: Fourteen free-living lactating women participated in a cross-over dietary intervention study, consuming a low fat diet (17.6% of energy as fat, 14.4% of energy as protein, 68.0% of energy as carbohydrate) and a high fat diet (40.3% of energy as fat, 14.4% of energy as protein, 45.3% of energy as carbohydrate) each for periods of 4 days, in randomised order. Each mother was her own control. Mature milk samples were collected during each period and analysed for medium and long chain fatty acids. RESULTS: The concentration of medium chain fatty acids (MCFA), was 13.6% in breast milk for the low fat diet compared to 11.4% for the high fat (p < 0.05). Arachidonic acid (C20:4n-6) levels were significantly higher in breast milk when women consumed the low fat diet. Increased dietary intake of stearic acid (C18:0) and alpha-linolenic acid (C18:3n-3) on the high fat diet significantly increased proportions of these fatty acids in breast milk (p < 0.05) in 4 days. CONCLUSIONS: Changing maternal dietary fat intake has a rapid response in terms of changes to fatty acids in breast milk.

Feeding a formula supplemented with long chain polyunsaturated fatty acids modifies the "ex vivo" cytokine responses to food proteins in infants at low risk for allergy.

Long chain polyunsaturates (LCP) status during the early neonatal period is associated with a reduced risk of atopic symptoms and later allergies. In this study, we characterized the immune response of low-risk, term, formula-fed infants randomized at

Effect of providing a formula supplemented with long-chain polyunsaturated fatty acids on immunity in full-term neonates.

To determine the effect of feeding formula containing long-chain PUFA (LCP) on immune function, healthy term infants were randomised at age 2 weeks to either a standard term formula (Formula; n 14) or the same formula supplemented with the LCP 20 : 4n-6 and 22 : 6n-3 (Formula+LCP; n 16). Peripheral blood was collected at 2 and 6 weeks to measure immune cell response (the rate of [3H]thymidine uptake and cytokine production after stimulation with phytohaemagglutinin (PHA)). Compared with cells from infants receiving only human milk (HM), the rate of [3H]thymidine uptake in response to PHA, but not IL-2 production, was lower for Formula+LCP infants (P < 0.05). Compared with HM-fed infants, Formula-fed infants (but not Formula+LCP infants) produced more TNF-alpha (unstimulated) and had a fewer CD3+CD44+ cells before stimulation and fewer CD11c+ cells post-stimulation (P < 0.05). However, compared with Formula-fed infants, the Formula+LCP infants had an immune cell distribution (higher percentage CD3+CD44+ and CD4+CD28+ cells) and cytokine profile (lower production of TNF-alpha post-stimulation) that did not differ from HM infants. Additionally, it was found that feeding infants formula during the first 10 d of life influenced immune function. These infants had a higher percentage of CD3+, CD4+CD28+, and lower percentage of CD14+ cells and produced more TNF-alpha and interferon-gamma after PHA stimulation than HM-fed infants (P < 0.05). These results demonstrate that early diet influences both the presence of specific cell types and function of infant blood immune cells. Since many diseases have a strong immunological component, these immune changes may be of physiological importance to the developing infant.

Postnatal dietary supplementation with either gangliosides or choline: effects on spatial short-term memory in artificially-reared rats.

This study addressed the hypothesis that dietary supplementation with either gangliosides or choline during the brain growth spurt would enhance short-term spatial memory. Male Long-Evans rats were reared artificially from postnatal days (PD) 5-18 and were fed diets containing either (i) choline chloride 1250 mg/l (CHL), (ii) choline chloride 250 mg/l and GD3 24 mg/l (GNG) or (iii) choline chloride 250 mg/l (STD). A fourth group (SCK) was reared normally. Rats were weaned onto AIN 93G diet and on PD 35 were trained on a cued delayed- matching-to-place version of the Morris water maze. All groups learned to swim to the beacon that indicated the platform position on the first trial; similarly, on the second un-cued trial, the distance swam to reach the platform decreased to the same extent in all groups over the five days of training. The groups also responded in the same way to an increase in delay between the first and second trial from 1 min to 1 h, showing an increase in the distance swam, accompanied by a decrease in the number of direct swims to the platform. Thus, all rats were equally proficient at using spatial short-term memory, regardless of the choline or ganglioside content of the preweaning diet.

The effect of treating infected skin grafts with Acticoat on immune cells.

A study was conducted to determine the effect of Acticoat placed on an infected skin graft on parameters of immunity. Two partial thickness wounds (2 cm x 4 cm) were created on the dorsal midline of Hartley guinea pigs (n=28). Wounds were covered with autologous skin graft and maintained either aseptically (Noninoculated, n=8), inoculated with Staphylococcus aureus (Surgery-Inoculated, n=8) with or without Acticoat bandage (Surgery-Inoculated-Acticoat, n=6). Five days later, splenocytes and blood were collected to estimate natural killer cell (NK) cytotoxicity, proliferative response to T and B cell mitogens and neutrophil oxidative burst. Animals that did not undergo surgery were included as a nonsurgery control group. [(3)H]-thymidine incorporation in response to a variety of T and B cell mitogens was significantly lower for all groups undergoing surgery compared to the nonsurgery control group (p<0.0001) and no additional effect was observed on this immune measure by applying the Acticoat bandage. The Surgery-Inoculated-Acticoat group exhibited greater NK cytotoxic activity (as assessed as the ability to lyse K562 tumor cells) compared to the Surgery-Inoculated group (p<0.006). The Surgery-Inoculated-Acticoat group had higher neutrophil oxidative burst at 5 min post stimulation, but was not different from controls after 15 min. In conclusion, the application of an Acticoat bandage to an inoculated surgery wound did not alter the low cell-mediated immune response that followed surgery, but appeared to increase parameters (NK cytotoxic activity and neutrophil function) of innate immunity.

Dietary gangliosides increase the content and molecular percentage of ether phospholipids containing 20:4n-6 and 22:6n-3 in weanling rat intestine.

This study was conducted to determine whether dietary ganglioside (GG) increases the content of ether phospholipids (EPL) in intestinal mucosa. Weanling Sprague-Dawley rats were fed a semipurified diet consisting of 20% fat as a control diet. Two experimental diets were formulated by adding either 0.1% (w/w fat) GGs (GG diet) or 1.0% (w/w fat) sphingomyelin (SM diet) to the control diet. Fatty acid methyl esters from the alkenylacyl, alkylacyl and diacyl subclasses of phospholipids were measured to determine total and molecular percentage of EPL comprising the choline phosphoglyceride (CPG) and ethanolamine phosphoglyceride (EPG) fraction. Animals fed the GG diet significantly increased total EPL content both in CPG (by 36%) and in EPG (by 66%), and the molecular percentage of EPL in CPG (by 76%) and in EPG (by 59%) compared to animals fed the control diet. Dietary GG-induced increase in EPL resulted in a higher level of polyunsaturated fatty acids (PUFA) specifically in 20:4n-6 and 22:6n-3 compared to control animals, leading to a decrease in the ratio of saturated fatty acids (SFA) to PUFA both in CPG and in EPG. Feeding animals the SM diet showed a higher level of EPL than control animals with a concomitant increase in 22:6n-3 in EPL. The present data demonstrate that dietary GG increases the content and composition of EPL containing PUFA in the weanling rat intestine.

20:5n-3 but not 22:6n-3 is a preferred substrate for synthesis of n-3 very-long- chain fatty acids (C24-C36) in retina.

The objective of this study was to determine if 20:5n-3 or 22:6n-3 is the primary precursor of very-long-chain fatty acids (VLCFAs; C24-C36) synthesized in retina. Rats were fed semisynthetic, nutritionally complete diet containing 20% (w/w) fat with 3% (w/w) of 22:6n-3. After 6 weeks feeding, the vitreal fluid of each eye was injected with [3H]20:5n-3 or [3H]22:6n-3. Rats were then maintained under constant light (330 lux) or dark conditions for 48 hr. After 48 hr in vivo metabolism, the amount of label present in individual fatty acids was determined in major phospholipids in retina. For [3H]22:6n-3, 90% of total incorporation remained in 22:6n-3, whereas for [3H]20:5n-3 the label was actively incorporated into pentaenoic and hexaenoic VLCFAs up to 34 carbon chain length. 22:5n-3 derived from [3H]20:5n-3 was among the most highly labeled fatty acids. These observations suggest that 22:6n-3 is incorporated directly into retinal phospholipids without further metabolism, whereas 20:5n-3 and 22:5n-3 are metabolically active precursors for synthesis of VLCFAs.

Dietary ganglioside and long-chain polyunsaturated fatty acids increase ganglioside GD3 content and alter the phospholipid profile in neonatal rat retina.

PURPOSE: During early development, the ganglioside composition of the retina changes significantly, in that GD3 becomes the primary ganglioside in the mammalian retina. Because gangliosides play an important role in neuronal cell differentiation and proliferation, this change in ganglioside profile may indicate retinal maturation. Dietary long-chain polyunsaturated fatty acids (LCPs) such as 20:4n-6 and 22:6n-3 improve visual acuity in infants. Dietary LCPs stimulate neonatal retinal development by altering membrane phospholipids, which in turn affect cell signaling pathways. It is unknown whether dietary ganglioside and LCPs affect the metabolism of phospholipids and gangliosides during retinal development. METHODS: Male Sprague-Dawley rats (18 days old) were fed semipurified diets consisting of 20% fat (control diet) for 2 weeks containing either 0.1% ganglioside enriched in GD3 (GG diet) or 1% 20:4n-6 and 0.5% 22:6n-3 (LCP diet) in the control diet. The profile of ganglioside and phospholipid was measured. RESULTS: The GG diet increased the ganglioside content by 39% in the retina, with a relative increase in GD3 (by 13%). Dietary LCPs significantly increased the relative levels of GD3 (by 19%, P < 0.01). Total phospholipid was decreased by the LCP-supplemented diet (by 28%). Phosphatidylcholine and phosphatidylserine increased with concomitant decreases in phosphatidylinositol and lyso-phosphatidylethanolamine when animals were fed either the LCP or the GG diet. CONCLUSIONS: Animals fed dietary ganglioside increased in total retinal ganglioside and GD3 content during retinal development, with a concomitant alteration of phospholipid metabolism. Feeding animals dietary LCPs also affected ganglioside metabolism in the developing retina, suggesting a new mechanism by which these dietary lipids may promote maturation of photoreceptor cells.

Dietary ganglioside decreases cholesterol content, caveolin expression and inflammatory mediators in rat intestinal microdomains.

Membrane microdomains rich in cholesterol and sphingolipids, including gangliosides (GGs), are known to be important regions for cell signaling and binding sites for various pathogens. Cholesterol depletion inhibits the cellular entry of pathogens and also reduces inflammatory signals by disrupting microdomain structure. Our previous study showed that dietary gangliosides increased total ganglioside incorporation while decreasing cholesterol in the intestinal mucosa. We hypothesized that diet-induced reduction in cholesterol content in the intestinal mucosa disrupts microdomain structure resulting in reduced pro-inflammatory signals. Male weanling Sprague-Dawley rats were fed semipurified diets for 2 weeks. Experimental diets were formulated to include either ganglioside-enriched lipid (GG diet, 0.02% gangliosides [w/w of diet] ) or polyunsaturated fatty acid (PUFA diet, 1% arachidonic acid and 0.5% docosahexaenoic acid, w/w of total fat), in a control diet containing 20% fat. Levels of cholesterol, GG, caveolin, platelet activating factor (PAF), and diglyceride (DG) were measured in the microdomain isolated from the intestinal brush border. The GG diet increased total gangliosides by 50% with a relative increase in GD3 and a relative decrease in GM3. Cholesterol content was also reduced by 23% in the intestinal microdomain. These changes resulted in a significant decrease in the ratio of cholesterol to ganglioside. The GG diet and the PUFA diet were both associated with reduction in caveolin, PAF, and DG content in microdomains, whereas no change occurred in the ganglioside profile of animals fed the PUFA diet. Dietary gangliosides decrease the cholesterol/ganglioside ratio, caveolin, PAF and DG content in microdomains thus exerting a potential anti-inflammatory effect during gut development.

Growth and development of preterm infants fed infant formulas containing docosahexaenoic acid and arachidonic acid.

OBJECTIVES: To evaluate safety and benefits of feeding preterm infants formulas containing docosahexaenoic acid (DHA) and arachidonic acid (ARA) until 92 weeks postmenstrual age (PMA), with follow-up to 118 weeks PMA. STUDY DESIGN: This double-blinded study of 361 preterm infants randomized across three formula groups: (1) control, no supplementation; (2) algal-DHA (DHA from algal oil, ARA from fungal oil); and (3) fish-DHA (DHA from fish oil, ARA from fungal oil). Term infants breast-fed > or =4 months (n = 105) were a reference group. Outcomes included growth, tolerance, adverse events, and Bayley development scores. RESULTS: Weight of the algal-DHA group was significantly greater than the control group from 66 to 118 weeks PMA and the fish-DHA group at 118 weeks PMA but did not differ from term infants at 118 weeks PMA. The algal-DHA group was significantly longer than the control group at 48, 79, and 92 weeks PMA and the fish-DHA group at 57, 79, and 92 weeks PMA but did not differ from term infants from 79 to 118 weeks PMA. Supplemented groups had higher Bayley mental and psychomotor development scores at 118 weeks PMA than did the control group. Supplementation did not increase morbidity or adverse events. CONCLUSIONS: Feeding formulas with DHA and ARA from algal and fungal oils resulted in enhanced growth. Both supplemented formulas provided better developmental outcomes than unsupplemented formulas.

Diet-induced changes in membrane gangliosides in rat intestinal mucosa, plasma and brain.

OBJECTIVES: The objective of this study was to determine if dietary gangliosides induce changes in the ganglioside content of intestinal mucosa, plasma and brain and to identify where GM3 and GD3 are localized in the enterocyte membrane. METHODS: Male 18-day-old Sprague-Dawley rats were fed a semipurified diet containing 20% (w/w) fat. The control diet contained triglyceride, reflecting the fat formulation of an existing infant formula. Two experimental diets were formulated by adding sphingomyelin (1% w/w of total fat) or a ganglioside-enriched lipid (0.1% w/w of total fat) to the control diet fat. The ganglioside fraction of ganglioside-enriched lipid diet contained more than 80% GD3. After 2 weeks of feeding, the total and individual ganglioside and cholesterol content was measured in small intestinal mucosa, plasma and brain. RESULTS: The ganglioside-enriched lipid diet significantly increased total gangliosides in the intestinal mucosa, plasma and brain compared with the control diet. The ganglioside-enriched lipid diet significantly increased the level of GD3 (7.5% w/w) in the intestine compared with control (3.2% w/w) while decreasing the level of GM3, the major ganglioside in the intestine. The ratio of cholesterol to ganglioside in the intestinal mucosa, plasma and brain decreased significantly in rats fed the ganglioside-enriched lipid diet compared with controls. Confocal microscopy showed that GM3 is exclusively localized in the apical membrane of the enterocyte whereas GD3 is primarily localized in the basolateral membrane. CONCLUSIONS: : The authors conclude that dietary ganglioside is absorbed in the small intestine and transported to different membrane sites, altering ganglioside levels in the intestinal mucosa, plasma and brain and thus possibly having the potential to change developing enterocyte function (and possibly that of other cell lines).