Depletion of essential fatty acids in muscle is associated with shorter survival of cancer patients undergoing surgery-preliminary report.

Emerging studies are reporting associations between skeletal muscle abnormalities and survival in cancer patients. Cancer prognosis is associated with depletion of essential fatty acids in erythrocytes and plasma in humans. However the relationship between skeletal muscle membrane fatty acid composition and survival is unknown. This study investigates the relationship between fatty acid content of phospholipids in skeletal muscle and survival in cancer patients. Rectus abdominis biopsies were collected during cancer surgery from 35 patients diagnosed with cancer. Thin-layer and gas chromatography were used for quantification of phospholipid fatty acids. Cutpoints for survival were defined using optimal stratification. Median survival was between 450 and 500 days when patients had arachidonic acid (AA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in muscle phospholipid below the cut-point compared to 720-800 days for patients above. Cox regression analysis revealed that low amounts of AA, EPA and DHA are risk factors for death. The risk of death remained significant for AA [HR 3.5 (1.11-10.87), p = 0.03], EPA [HR 3.92 (1.1-14.0), p = 0.04] and DHA [HR 4.08 (1.1-14.6), p = 0.03] when adjusted for sex. Lower amounts of essential fatty acids in skeletal muscle membrane is a predictor of survival in cancer patients. These results warrant investigation to restore bioactive fatty acids in people with cancer.

Lipid is heterogeneously distributed in muscle and associates with low radiodensity in cancer patients.

BACKGROUND: Low muscle radiodensity is associated with mortality in a variety of cancer types. Biochemical and morphological correlates are unknown. We aimed to evaluate triglyceride (TG) content and location as a function of computed tomography (CT)-derived measures of skeletal muscle radiodensity in cancer patients. METHODS: Rectus abdominis (RA) biopsies were collected during cancer surgery from 75 patients diagnosed with cancer. Thin-layer chromatography and gas chromatography were used for quantification of TG content of the muscle. Axial CT images of lumbar vertebra were used to measure muscle radiodensity. Oil Red O staining was used to determine the location of neutral lipids in frozen muscle sections. RESULTS: There was wide variation in RA radiodensity in repeated measures (CV% ranged from 3 to 55% based on 10 serial images) as well as within one slice (CV% ranged from 6 to 61% based on 10 subregions). RA radiodensity and total lumbar muscle radiodensity were inversely associated with TG content of RA (r = -0.396, P < 0.001, and r = -0.355, P = 0.002, respectively). Of the total percentage area of muscle staining positive for neutral lipid, 54 ± 17% was present as extramyocellular lipids (range 23.5-77.8%) and 46 ± 17% (range 22.2-76.5%) present as intramyocellular lipid droplets. CONCLUSIONS: Repeated measures revealed wide variation in radiodensity of RA muscle, both vertically and horizontally. Low muscle radiodensity reflects high level of TG in patients with cancer. Non-uniform distribution of intramyocellular and extramyocellular lipids was evident using light microscopy. These results warrant investigation of mechanisms resulting in lipid deposition in muscles of cancer patients.

Reduction of Arachidonate Is Associated With Increase in B-Cell Activation Marker in Infants: A Randomized Trial.

BACKGROUND: Infants who are not breast-fed benefit from formula with both docosahexaenoic acid (C22:6n3) and arachidonic acid (ARA; C20:4n6). The amount of ARA needed to support immune function is unknown. Infants who carry specific fatty acid desaturase (FADS) polymorphisms may require more dietary ARA to maintain adequate ARA status. OBJECTIVE: The aim of the study was to determine whether ARA intake or FADS polymorphisms alter ARA levels of lymphocytes, plasma, and red blood cells in term infants fed infant formula. METHODS: Infants (N = 89) were enrolled in this prospective, double-blind controlled study. Infants were randomized to consume formula containing 17 mg docosahexaenoic acid and 0, 25, or 34 mg ARA/100 kcal for 10 weeks. Fatty acid composition of plasma phosphatidylcholine and phosphatidylethanolamine, total fatty acids of lymphocytes and red blood cells, activation markers of lymphocytes, and polymorphisms in FADS1 and FADS2 were determined. RESULTS: Lymphocyte ARA was higher in the 25-ARA formula group than in the 0- or 34-ARA groups. In plasma, 16:0/20:4 and 18:0/20:4 species of phosphatidylcholine and phosphatidylethanolamine were highest and 16:0/18:2 and 18:0/18:2 were lowest in the 34-ARA formula group. In minor allele carriers of FADS1 and FADS2, plasma ARA content was elevated only at the highest level of ARA consumed. B-cell activation marker CD54 was elevated in infants who consumed formula containing no ARA. CONCLUSIONS: ARA level in plasma is reduced by low ARA consumption and by minor alleles in FADS. Dietary ARA may exert an immunoregulatory role on B-cell activation by decreasing 16:0/18:2 and 18:0/18:2 species of phospholipids. ARA intake from 25 to 34 mg/100 kcal is sufficient to maintain cell ARA level in infants across genotypes.

Pretreatment with an intravenous lipid emulsion increases plasma eicosapentanoic acid and downregulates leukotriene b4, procalcitonin, and lymphocyte concentrations after open heart surgery in infants.

BACKGROUND: The effect of providing a lipid emulsion containing medium-chain triglyceride (MCT), soybean oil, and fish oil in critically ill infants is not widely studied. This study investigated lipid emulsion effects on plasma phospholipids and immune biomarkers. MATERIALS AND METHODS: Thirty-two infants undergoing cardiopulmonary bypass (CPB) and dependent on parenteral nutrition (PN) were randomized to receive either soybean oil (control, n = 16) or a 50:40:10 mixture of MCT, soybean oil, and fish oil (treatment, n = 16). PN was administered for 3 days preoperatively and 10 days postoperatively. Fatty acids, procalcitonin (PCT), leukotriene B4 (LTB4), and lymphocytes were quantified at baseline, before surgery, and days 1, 7 and 10 after surgery. RESULTS: PCT was significantly lower in the treatment vs control group 1 day postoperatively (P = .01). The treatment group exhibited a lower ω-6 to ω-3 ratio (P = .0001) and a higher ω-3 concentration at all postoperative study periods (P = .001). Treatment resulted in higher (P < .05) plasma phospholipid eicosapentaenoic acid (EPA) on days 7 and 10, while α-linolenic acid, arachidonic acid, and docosahexaenoic acid remained constant. An increase in plasma phospholipid EPA concentration was associated with a decrease in plasma phospholipid LTB4 concentration (P < .05). On postoperative day 10, treatment infants with high Pediatric Risk of Mortality III scores exhibited a 45% lower lymphocyte concentration (P < .05). CONCLUSION: These findings suggest that treating infants undergoing CPB with a lipid emulsion containing ω-3 improves fatty acid status and results in a lower inflammatory response after surgery. Overall, this alternative ω-3-enriched lipid emulsion may benefit clinical outcomes of critically ill infants after cardiac surgery.

De novo lipogenesis and cholesterol synthesis in humans with long-standing type 1 diabetes are comparable to non-diabetic individuals.

BACKGROUND: Synthesis of lipid species, including fatty acids (FA) and cholesterol, can contribute to pathological disease. The purpose of this study was to investigate FA and cholesterol synthesis in individuals with type 1 diabetes, a group at elevated risk for vascular disease, using stable isotope analysis. METHODS: Individuals with type 1 diabetes (n = 9) and age-, sex-, and BMI-matched non-diabetic subjects (n = 9) were recruited. On testing day, meals were provided to standardize food intake and elicit typical feeding responses. Blood samples were analyzed at fasting (0 and 24 h) and postprandial (2, 4, 6, and 8 hours after breakfast) time points. FA was isolated from VLDL to estimate hepatic FA synthesis, whereas free cholesterol (FC) and cholesteryl ester (CE) was isolated from plasma and VLDL to estimate whole-body and hepatic cholesterol synthesis, respectively. Lipid synthesis was measured using deuterium incorporation and isotope ratio mass spectrometry. RESULTS: Fasting total hepatic lipogenesis (3.91 ± 0.90% vs. 5.30 ± 1.22%; P = 0.41) was not significantly different between diabetic and control groups, respectively, nor was synthesis of myristic (28.60 ± 4.90% vs. 26.66 ± 4.57%; P = 0.76), palmitic (12.52 ± 2.75% vs. 13.71 ± 2.64%; P = 0.65), palmitoleic (3.86 ± 0.91% vs. 4.80 ± 1.22%; P = 0.65), stearic (5.55 ± 1.04% vs. 6.96 ± 0.97%; P = 0.29), and oleic acid (1.45 ± 0.28% vs. 2.10 ± 0.51%; P = 0.21). Postprandial lipogenesis was also not different between groups (P = 0.38). Similarly, fasting synthesis of whole-body FC (8.2 ± 1.3% vs. 7.3 ± 0.8%/day; P = 0.88) and CE (1.9 ± 0.4% vs. 2.0 ± 0.3%/day; P = 0.96) and hepatic FC (8.2 ± 2.0% vs. 8.1 ± 0.8%/day; P = 0.72) was not significantly different between diabetic and control subjects. CONCLUSIONS: Despite long-standing disease, lipogenesis and cholesterol synthesis was not different in individuals with type 1 diabetes compared to healthy non-diabetic humans.

Elevated lipogenesis and diminished cholesterol synthesis in patients with hepatitis C viral infection compared to healthy humans.

UNLABELLED: Hepatitis C virus (HCV) exerts a profound influence on host lipid metabolism. It has been suggested that the synthesis of both fatty acids (FA) and cholesterol is dysregulated in HCV but this has not been directly quantified in humans. The purpose of this study was to measure lipogenesis and cholesterol synthesis using stable isotopes in patients with HCV (n = 5) and healthy control (n = 9) subjects recruited from the University of Alberta hospital. Blood samples were taken at fasting (0 and 24 hours) and after meals over the day to mimic typical food consumption and postprandial metabolism. Isolation of free cholesterol (FC), cholesteryl ester (CE), and triglyceride (TG) from plasma and very low-density lipoproteins (VLDL) was used to measure FA and cholesterol synthesis using deuterium uptake and isotope ratio mass spectrometry. FA composition was analyzed by gas chromatography. VLDL-TG levels of polyunsaturated fatty acids (PUFA), including linoleic and linolenic acid, were lower in HCV compared to control (P < 0.05 for both). Fasting hepatic lipogenesis was significantly higher in HCV (2.80 ± 0.55%) compared to control (1.19 ± 0.27%; P = 0.03). Conversely, fasting whole-body synthesis of FC (HCV 1.64 ± 0.28% versus control 8.78 ± 1.59%) and CE (HCV 0.26 ± 0.08% versus control 1.92 ± 0.25%), as well as hepatic FC synthesis (HCV 1.68 ± 0.26% versus control 8.12 ± 0.77%) was lower in HCV (P < 0.001 for all). CONCLUSION: These data provide evidence that lipogenesis is elevated while cholesterol synthesis is impaired in HCV, supporting previous findings from cellular and animal models. Low PUFA levels combined with elevated lipogenesis suggests a role for dietary PUFA supplementation in HCV patients.

Low energy intakes are associated with adverse outcomes in infants after open heart surgery.

BACKGROUND: Infants with congenital heart lesions who undergo open heart surgery may experience physiologic and metabolic stress in the postoperative period, leading to altered metabolism and hypercatabolism. The purpose of this study was to determine the relationship between energy intake and hospital outcomes during the first 10 days following neonatal open heart surgery. MATERIALS AND METHODS: A post hoc analysis of all patients in a prospective randomized controlled trial was performed. Nutrition intake and hospital outcomes were assessed in 32 infants (40 ± 2.2 weeks, 3.4 ± 0.5 kg) in the neonatal and pediatric intensive care units. Infants received parenteral nutrition (PN) for 1-4 days before and 10 days after open heart surgery. Infants were separated into those who received a cumulative energy intake of <689 kcal (average 63 kcal/kg/d) and those who received an intake ≥689 kcal during postoperative days 0-10. RESULTS: Lower energy intake was associated with a significantly increased duration of artificial ventilation (5 ± 1.2 days), time to chest closure (1.4 ± 0.5 days), time in intensive care (5 ± 1.8 days), and stay in the hospital (25 ± 6.4 days). Lower energy intake was also associated with a significant increase in the length of time infants required PN (8 ± 2.9 days) and longer time to achieve full enteral intake of 100 mL/kg/d (7 ± 2.2 days) and before enteral feeds could be initiated (5 ± 1.5 days). CONCLUSIONS: Providing <63 kcal/kg/d to infants after open heart surgery was associated with adverse pediatric intensive care outcomes.

Dietary docosahexaenoic acid supplementation prevents age-related functional losses and A2E accumulation in the retina.

PURPOSE: With age, retina function progressively declines and A2E, a constituent of the toxin lipofuscin, accumulates in retinal pigment epithelial (RPE) cells. Both events are typically exacerbated in age-related retina diseases. We studied the effect of dietary docosahexaenoic acid (DHA, C22:6n-3) supplementation on these events, using a transgenic mouse model (mutant human ELOVL4; E4) displaying extensive age-related retina dysfunction and massive A2E accumulation. METHODS: Retina function was assessed with the electroretinogram (ERG) and A2E levels were measured in E4 and wildtype (WT) mice. Dietary DHA was manipulated from 1 to 3, 1 to 6, 6 to 12, and 12 to 18 months: 1% DHA over total fatty acids (E4+, WT+) or similar diet without DHA (E4-, WT-). RESULTS: Increased omega-3/6 ratios (DHA/arachidonic acid) in E4+ and WT+ retinas were confirmed for the 1- to 3-month and 1- to 6-month trials. Although 1- to 3-month intervention had no effects, when prolonged to 1 to 6 months, RPE function (ERG c-wave) was preserved in E4+ and WT+. Intervention from 6 to 12 months led to maintained outer and inner retina function (ERG a- and b-wave, respectively) in E4+. At 12 to 18 months, a similar beneficial effect on retina function occurred in WT+; A2E levels were reduced in E4+ and WT+. CONCLUSIONS: DHA supplementation was associated with: preserved retina function at mid-degenerative stages in E4 mice; prevention of age-related functional losses in WT mice; and reduced A2E levels in E4 and WT mice at the oldest age examined. These findings imply that dietary DHA could have broad preventative therapeutic applications (acting on pathologic and normal age-related ocular processes).

Pre-treatment with an intravenous lipid emulsion containing fish oil (eicosapentaenoic and docosahexaenoic acid) decreases inflammatory markers after open-heart surgery in infants: a randomized, controlled trial.

BACKGROUND & AIMS: This study assessed the effects of administering a lipid emulsion containing eicosapentaenoic and docosahexaenoic acid before and after open-heart surgery on cytokine production and length of hospital stay in infants. METHODS: Thirty-two infants (40 ± 2.3 weeks gestational age; 10.6 days at time of surgery) undergoing open-heart surgery with cardiopulmonary bypass were randomized to receive an intravenous lipid emulsion with (treatment) or without (control) eicosapentaenoic and docosahexaenoic acid in this prospective, randomized, double-blind, controlled trial. RESULTS: Mean plasma TNF-α concentration was significantly (p = 0.003) lower in the treatment (5.9 pg/mL) compared to the control group (14.8 pg/mL). In infants without sepsis, plasma TNF-α did not differ according to treatment, however when sepsis developed, mean plasma TNF-α was 21.1 pg/mL and 1.5 pg/mL (p = 0.0007) in control and treatment groups, respectively. Plasma TNF-α was positively correlated with length of hospital stay in the control group (p = 0.01), and negatively correlated with length of stay in the treatment group (p = 0.004), with a significant time by treatment interaction (p = 0.02). CONCLUSIONS: Providing a lipid emulsion containing eicosapentaenoic and docosahexaenoic acid reduces TNF-α concentrations in infants undergoing open-heart surgery. Lipid emulsions containing eicosapentaenoic and docosahexaenoic acid may ameliorate the inflammatory response among critically ill infants.

Cholesterol ester and free fatty acids are modulated by policosanol in CaCo-2 intestinal cells.

OBJECTIVE: To investigate policosanol absorption by brush border membrane (BBM), metabolism in CaCo-2 enterocytes, and transport of policosanol metabolites across the basolateral membrane (BLM). It was hypothesized that policosanol is partially oxidized into fatty acids and then is incorporated into other lipids. METHODS: Policosanol was emulsified with phosphatidylcholine in the culture medium. The viability of cells was assessed via an MTT (3-[4,5]dimethylthiazol-2-yl-2,5-diphenyltetrazolim) assay. Control cells received only the same amount of "vehicle" (phosphatidylcholine) without policosanol. CaCo-2 cell monolayer and medium were collected; lipid was extracted and analyzed by thin-layer chromatography (TLC) and gas liquid chromatography (GLC). RESULTS: Eighty-six percent of policosanol added to the cell culture medium was absorbed after 48 hours' incubation. The amount of cholesterol ester fatty acid was significantly increased both in the cells and in the basolateral medium, and was reduced in the apical medium. Policosanol increased the quantity of free fatty acids in the basolateral medium and reduced the free fatty acid content of CaCo-2 cells. Further evaluation of lipid profiles indicated that policosanol modulated the fatty acid profile of cholesterol ester in the basolateral medium. CONCLUSION: It was concluded that policosanol or policosanol metabolites may modulate lipid metabolism and/or transport following absorption by the BBM, partial oxidation by the intestinal epithelium, and transport of policosanol metabolites across the BLM.

Dietary inadequacy is associated with anemia and suboptimal growth among preschool-aged children in Yunnan Province, China.

This study documented the relationships among dietary intake, growth failure, and anemia in a convenience sample of 172 children aged 1 to 5 years in rural Yunnan Province, China. We hypothesized that most children would have suboptimal intakes of key nutrients associated with child growth and anemia and that undernutrition would be more common in children with poor growth and in those who were anemic. Nutrient intakes from three 24-hour recalls were compared with the Dietary Reference Intakes. Height/length and weight were compared with World Health Organization Child Growth Standards to determine if children were malnourished (z score < -2 SD median). Blood was tested for anemia (hemoglobin <110 g/L). Stunting, underweight, wasting, and anemia were present among 44.4%, 15.7%, 1.7%, and 35.4% of children, respectively. The percentage of children not meeting the estimated average requirement for zinc, vitamin A, iron, and protein or the adequate intake for calcium was 87.2%, 80.8%, 66.3%, 7.6%, and 100.0%, respectively. Altogether, 19.2% and 78.5% of children were below the acceptable macronutrient distribution range for percentage of energy from protein and fat, respectively. More stunted than not stunted children were below the estimated average requirement for vitamin A, as were more anemic than nonanemic children. Growth faltering combined with findings of anemia and suboptimal intake of a variety of nutrients suggests a high prevalence of chronic dietary inadequacy among preschool-aged children in Yunnan Province. Consuming more protein-, fat-, zinc-, iron-, and vitamin A-rich foods may improve growth and reduce anemia.

Protection of intestinal occludin tight junction protein by dietary gangliosides in lipopolysaccharide-induced acute inflammation.

OBJECTIVES: Intestinal permeability and barrier function are regulated by expression of tight junction proteins. Lipopolysaccharide (LPS), tumor necrosis factor-alpha, and interleukin-1beta induce expression of nitric oxide (NO) and reduce the expression of gut tight junction proteins. The purpose of this study was to determine whether dietary gangliosides (GGs) increase the concentration of the anti-inflammatory cytokine interleukin-10 (IL-10) in response to LPS, thereby inhibiting NO production and protecting gut occludin tight junction protein from degradation. MATERIALS AND METHODS: Rats were fed semipurified diets with (n = 16) or without (n = 16) GGs (0.1% w/w of total lipid). After 2 weeks of feeding, animals were injected with saline (n = 8/diet group) or LPS (n = 8/diet group) (IP, 3 mg mL(-1) kg(-1)). Intestinal tissue, mucosa, and blood sample were collected 6 hours post-LPS exposure. The effect of dietary GGs on production/expression of IL-10, NO, inducible NO synthase, and occludin protein was determined. RESULTS: Dietary GGs increased IL-10 content in intestinal mucosa significantly by 32-fold (P < 0.0001) and in plasma by 2.4-fold (P < 0.001). Feeding animals a ganglioside-enriched diet decreased total NO content in intestinal mucosa and plasma by 44% and 30%, respectively, and inhibited inducible NO synthase expression following LPS exposure compared with control animals. Dietary GGs reduced the degradation of occludin tight junction protein in response to LPS. CONCLUSIONS: Dietary GGs inhibit degradation of gut occludin tight junction protein during LPS-induced acute inflammation. Thus, dietary GGs have a role in protecting the integrity of the intestinal barrier during acute gut inflammation.

Gangliosides protect bowel in an infant model of necrotizing enterocolitis by suppressing proinflammatory signals.

OBJECTIVES: Necrotizing enterocolitis (NEC) has high morbidity in premature infants. Hypoxia-ischemia, infection, and enteral feeding are risk factors associated with NEC, whereas feeding human milk is protective. Vasoactive and inflammatory mediators in NEC remain elusive. Gangliosides are found in human milk and enterocyte membranes. An infant bowel model of NEC was developed to test the hypothesis that gangliosides modulate the inflammatory response to infection and hypoxia. PATIENTS AND METHODS: Viable, noninflamed bowel was obtained from 9 infants between 26 and 40 weeks' gestational age. Infant bowel was treated in culture with Escherichia coli lipopolysaccharide (LPS) and hypoxia in the presence or absence of preexposure to gangliosides. Bowel necrosis and production of nitric oxide, endothelin-1, serotonin, eicosanoids, hydrogen peroxide, and proinflammatory cytokines were measured. RESULTS: Ganglioside preexposure reduced bowel necrosis and endothelin-1 production in response to LPS. Gangliosides suppressed infant bowel production of nitric oxide, leukotriene B4, prostaglandin E2, hydrogen peroxide, interleukin-1beta, interleukin-6, and interleukin-8 in response to LPS exposure and hypoxia. CONCLUSIONS: A bowel protective effect of gangliosides is indicated by modulation of vasoactive mediators and proinflammatory signal suppression.

Dietary assessment of arachidonic acid and docosahexaenoic acid intake in 4-7 year-old children.

OBJECTIVE: To investigate current dietary intakes of arachidonic acid (AA), docosahexaenoic acid (DHA) in healthy children between 4-7 years of age using a 3-day food record. DESIGN: Cross-sectional study investigating dietary intakes using food records. Parents were instructed to document all food and drink consumed by their child for 3 consecutive days. SUBJECTS AND SETTING: Healthy children (n = 91), 4-7 years of age, living in central Alberta, Canada were volunteered by their parents to participate in the study. Seventy-eight children completed the study. RESULTS: AA and DHA intakes were 57 +/- 35 mg/day and 37 +/- 63 mg/day, ranged between 1.2-180 mg/day and 0-350 mg/day and varied day to day at 0-380 mg/day and 0-991 mg/d, respectively. DHA intake was

Uptake and fate of ganglioside GD3 in human intestinal Caco-2 cells.

Ganglioside GD3 is a glycosphingolipid found in colostrum, developing tissues, and tumors and is known to regulate cell growth, differentiation, apoptosis, and inflammation. Feeding a GD3-enriched diet to rats increases GD3 in intestinal lipid rafts and blood. The mechanism, efficiency, and fate of ganglioside absorption by human enterocytes have not been investigated. A model to study GD3 uptake by human intestinal cells was developed to test the hypothesis that enterocyte GD3 uptake is time and concentration dependent, with uptake efficiency and fate influenced by route of delivery. Caco-2 cells were exposed to GD3 on the apical or basolateral membrane (BLM) side for 6, 24, and 48 h. GD3 uptake, retention, transfer, and metabolism was determined. GD3 uptake across the apical and BLM was time and concentration dependent and reached a plateau. GD3 uptake across the BLM was more efficient than apical delivery. Apical GD3 was metabolized with some cell retention and transfer, whereas basolateral GD3 was mostly metabolized. This study demonstrates efficient GD3 uptake by enterocytes and suggests that the route of delivery influences ganglioside uptake and fate.

Necrotizing enterocolitis: a multifactorial disease with no cure.

Necrotizing enterocolitis is an inflammatory bowel disease of neonates with significant morbidity and mortality in preterm infants. Due to the multifactorial nature of the disease and limitations in disease models, early diagnosis remains challenging and the pathogenesis elusive. Although preterm birth, hypoxic-ischemic events, formula feeding, and abnormal bacteria colonization are established risk factors, the role of genetics and vasoactive/inflammatory mediators is unclear. Consequently, treatments do not target the specific underlying disease processes and are symptomatic and surgically invasive. Breast-feeding is the most effective preventative measure. Recent advances in the prevention of necrotizing enterocolitis have focused on bioactive nutrients and trophic factors in human milk. Development of new disease models including the aspect of prematurity that consistently predisposes neonates to the disease with multiple risk factors will improve our understanding of the pathogenesis and lead to discovery of innovative therapeutics.

Maternal dietary 22 : 6n-3 is more effective than 18 : 3n-3 in increasing the 22 : 6n-3 content in phospholipids of glial cells from neonatal rat brain.

One of the debates in infant nutrition concerns whether dietary 18 : 3n-3 (linolenic acid) can provide for the accretion of 22 : 6n-3 (docosahexaenoic acid, DHA) in neonatal tissues. The objective of the present study was to determine whether low or high 18 : 3n-3 v. preformed 22 : 6n-3 in the maternal diet enabled a similar 22 : 6n-3 content in the phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI) and phosphatidylserine (PS) of glial cells from whole brain (cerebrum and cerebellum) of 2-week-old rat pups. At parturition, the dams were fed semi-purified diets containing either increasing amounts of 18 : 3n-3 (18 : 2n-6 to 18 : 3n-3 fatty acid ratio of 7.8 : 1, 4.4 : 1 or 1 : 1), preformed DHA, or preformed 20 : 4n-6 (arachidonic acid)+DHA. During the first 2 weeks of life, the rat pups from the respective dams received only their dam's milk. The fatty acid composition of the pups' stomach contents (dam's milk) and phospholipids from glial cells were quantified. The 20 : 4n-6 and 22 : 6n-3 content in the stomach from rat pups at 2 weeks of age reflected the fatty acid composition of the dam's diet. The 20 : 4n-6 content of PE and PS in the glial cells was unaffected by maternal diet treatments. Preformed 22 : 6n-3 in the maternal diet increased the 22 : 6n-3 content of glial cell PE and PS compared with maternal diets providing an 18 : 2n-6 to 18 : 3 n-3 fatty acid ratio of 7.8 : 1, 4.4 : 1 or 1 : 1 (P<0.0001). There was no significant difference in the 20 : 4n-6 and 22 : 6n-3 content of glial cell PC and PI among maternal diet treatments. It was concluded that maternal dietary 22 : 6n-3 is more effective than low or high levels of maternal dietary 18 : 3n-3 at increasing the 22 : 6n-3 content in PE and PS of glial cells from the whole brain of rat pups at 2 weeks of age. The findings from the present study have important implications for human infants fed infant formulas that are devoid of 22 : 6n-3.

Dietary low linolenic acid compared with docosahexaenoic acid alter synaptic plasma membrane phospholipid fatty acid composition and sodium-potassium ATPase kinetics in developing rats.

The objective of this study was to investigate if maternal dietary 20:4n-6 arachidonic acid (AA) and 22:6n-3 compared with adequate or low levels of 18:3n-3 linolenic acid (LNA) increases synaptic plasma membrane (SPM) cholesterol and phospholipid content, phospholipid 20:4n-6 and 22:6n-3 content, and Na,K-ATPase kinetics in rat pups at two and five weeks of age. At parturition, Sprague-Dawley rats were fed semi-purified diets containing either AA + docosahexaenoic acid (DHA), adequate LNA (control; 18:2n-6 : 18:3n-3 ratio of 7.1 : 1) or low LNA (18:2n-6 : 18:3n-39 ratio of 835 : 1). During the first two weeks of life, the rat pups received only their dams' milk. After weaning, pups received the same diet as their respective dams to five weeks of age. No significant difference was observed among rat pups fed the diet treatments for SPM cholesterol or total and individual phospholipid content at two and five weeks of age. Fatty acid analysis revealed that maternal dietary AA + DHA, compared with feeding the dams the control diet or the low LNA diet, increased 20:4n-6 in phosphatidylserine and 22:6n-3 content of SPM phospholipids. Rats fed dietary AA + DHA or the control diet exhibited a significantly increased Vmax for SPM Na,K-ATPase. Diet treatment did not alter the Km (affinity) of SPM Na,K-ATPase in rat pups at two and five weeks of age. It is concluded that dietary AA + DHA does not alter SPM cholesterol and phospholipid content but increases the 22:6n-3 content of SPM phospholipids modulating activity of Na,K-ATPase.