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Background: Apolipoprotein E (apoE) and cholesterol play a critical role in synapse and myelin maintenance and integrity and are thus appealing candidates in the pathogenesis of schizophrenia and bipolar disorder. To explore the role of these 2 molecules, we quantified cholesterol and apoE levels in prefrontal grey and white matter in patients with schizophrenia, bipolar disorder and healthy controls. Furthermore, we investigated the relations between apoE and cholesterol levels and the APOE genotype. Methods: We obtained dorsolateral prefrontal grey and white matter from the Stanley Medical Research Institute Brain Collection (schizophrenia n = 35, bipolar disorder n = 35 and controls n = 35). Cholesterol levels were quantified using high- pressure liquid chromatography, whereas apoE was measured by enzyme-linked immunosorbent assay. Results: We found no significant differences in cholesterol or apoE levels among the groups. ApoE levels were higher in grey matter than in white matter in all groups; conversely, levels of cholesterol were higher in white matter than in grey matter. We observed a significant inverse correlation between apoE and cholesterol levels in both grey and white matter. Furthermore, in grey matter, apoE levels were significantly higher in APOE ζ2 carriers compared with APOE ζ3 or APOE ζ4 carriers, with cholesterol levels following the opposite trend. Limitations: Limitations of our study include our inability to control for potential confounding variables and the small numbers of APOE ζ2 and ζ4 carriers in each group. Conclusion: Although large amounts of cholesterol are present in white matter, apoE expression is limited. The APOE genotype may play a role in the regulation of both cholesterol and apoE levels in grey matter. The impact of APOE polymorphisms on lipid homeostasis in people with psychiatric disorders warrants further investigation., Introduction Schizophrenia and bipolar disorder are complex illnesses. Although the molecular and cellular pathology of these disorders has not yet been fully elucidated, alterations in synapses, dendritic spines and myelin [...]

The long-chain polyunsaturated n-6 and n-3 fatty acids are essential nutrients in membrane biogenesis and regulate gene expression via their eicosanoid metabolites. We investigated whether the n-6 and n-3 fatty acid supply as determined by maternal diet alters colonic phospholipid fatty acids, intestinal morphology, and epithelial barrier permeability during milk feeding with lasting effect on mucosal responsiveness to dinitrobenzene sulfonic acid (DNBS)-induced colitis in young adulthood. Female rats were fed diets with 20% energy from safflower oil (SO) or canola oil (CO), or 8% fish oil (FO) plus 2% SO (10% FO) or 18% FO plus 2% SO (20% FO) throughout gestation and lactation and offspring weaned to a standard diet at 21 days of age. At 15 days of age, pups in the 20% and 10% FO groups had lower 20:4n-6 and higher 20:5n-3 and 22:6n-3 in colon phospholipids (P < 0.01), shorter crypts (P < 0.05), and higher paracellular permeability than SO or CO groups. At 3 mo of age, male offspring in the FO groups showed lasting reduction of crypt depth and a heightened inflammatory response to DNBS. We demonstrate that early decreased colon 20: 4n-6 with increased n-3 fatty acids impairs intestinal barrier development and sensitizes the colon response to inflammatory insults later in life. n-6 fatty acids; n-3 fatty acids; arachidonic acid; milk fatty acids; intestinal programming; inflammatory bowel disease doi: 10.1152/ajpgi.00258.2010.

Alterations in lipid metabolism may contribute to the pathology of hyperhomocysteinemia (HHcy). Our objective in this study was to test the hypothesis that HHcy is associated with changes in liver acyl CoA:cholesterol acyltransferase 2 (ACAT2) expression and cholesteryl esters (CE) in mice with HHcy. ACAT2 is encoded by Soar2 and functions to catalyze the esterification of cholesterol with acyl-CoA. Mice heterozygous for disruption of the cystathionine-[beta]-synthase gene (Cbs +/-) and C57BL/6 mice (Cbs +/+) were fed a control diet or a diet high in L-methionine (8.60 g/kg) and low in folic acid (0.20 mg/kg) to induce HHcy (HH diet). Lower Soat2 mRNA (P < 0.05) and ACAT protein (P < 0.001), higher total oleic acid [18:1(n-9)], and lower CE 18:1(n-9) was found in liver from Cbs +/- mice fed the HH diet, with higher plasma total homocysteine concentrations, than Cbs +/+ mice fed the control diet (35.01 [+ or -] 5.6 vs. 2.21 [+ or -] 0.6 [micro]mol/L, respectively). In silico searches identified a CpG-rich region in the 5' portion of the Soat2 gene, which was differentially methylated (P < 0.05) in Cbs +/- mice fed the HH diet than in Cbs +/+ mice fed the control diet and was accompanied by higher (P < 0.05) B1 repeat element methylation, an indicator of global de novo methylation. These findings show altered methylation and expression of Soat2/ACAT2 in liver from mice with HHcy and suggest a role for changes in liver CE in the pathology of HHcy. J. Nutr. 140: 231-237, 2010. doi: 10.3945/jn.109.112920.

Arachidonic [ARA, 20:4(n-6)], eicosapentaenoic [EPA, 20:5(n-3)], and docosahexaenoic acids [DHA, 22:6(n-3)] occur in the diet in animal tissue lipids, play important roles in human development and health, but have interactive and opposing functions. Meat and poultry have higher ARA and fish are richer in EPA and DHA. National databases were recently revised to include complete data on ARA in foods. We used a validated FFQ and the revised nutrient databases to quantify the distribution of ARA, EPA, and DHA intakes and balance for 204 healthy Canadian pregnant women. We focused on intake distributions because risk of adverse health effects increases at lower nutrient intakes. RBC fatty acids were analyzed concurrenly with dietary assessment. The distribution of ARA, EPA, and DHA intakes were skewed (P < 0.001), with a median (5-95th percentile) of 107 (41-225), 65 (10-228), and 105 (10-430) mg/d ARA, EPA, and DHA, respectively. Fish provided 66 and 76% of EPA and DHA, respectively, whereas eggs, poultry, and meats provided 81% of ARA. Women consuming Manuscript received July 6, 2009. Initial review completed August 25, 2009. Revision accepted October 14, 2009. First published online October 28, 2009; doi: 10.3945/jn.109.112565.

Inflammatory bowel diseases are life-long reoccurring inflammatory disorders of the gastrointestinal tract and have been increasing in incidence in recent decades, notably in the pediatric population. Although genetic predisposition remains an important factor, this increased incidence most likely reflects an environmental change. One potential contributor to this is the change in dietary fat intake, with dietary intake of n-6 polyunsaturated fatty acids (PUFAs) following a similar temporal pattern to the change in inflammatory bowel disease incidence. Dietary n-6 PUFAs comprise a major, modifiable, environmental factor known to protnote a heightened inflammatory response through a number of pathways, including their role as precursors for synthesis of eicosanoids and their inhibitory effect on the synthesis of the n-3 PUFAs eicosapentanoic acid and docosahexanoic acid. The increase in n-6 PUFA intake affects individuals of all ages, with fetal PUFA accretion and infant dietary PUFA intake from breast milk reflecting maternal dietary intake. A high level of n-6 PUFA in milk results in increased n-6 PUFA in colonic phospholipids and an exaggerated inflammatory response to chemically induced colitis. Conversely, during development, a diet low in n-6 PUFAs and high in n-3 PUFAs increases colonic n-3 fatty acids, attenuates the inflammatory response, and lowers colonic damage. High dietary n-6 PUFA intake may be an important environmental modifier that contributes to inflammatory bowel diseases. Key words: pediatric, maternal, ulcerative colitis, Crohn's disease, n-3 PUFA, n-6 PUFA, linoleic acid, arachidonic acid, interleukin, tumor necrosis factor, [alpha]-inoleic acid, eicosapentanoic acid, docosahexanoic acid doi: 10.1301/nr.2007.dec.S188-S193

Choline and glycine are inter-related through their roles in methyl metabolism. Choline is metabolized to betaine, which donates a methyl group to homocysteine to form methionine, also generating dimethylglycine, which is further metabolized to glycine. Choline is transported across the placenta and is higher in fetal than maternal plasma. Placental glycine transfer, however, is limited and poor glycine status has been suggested in preterm infants. Insufficient glycine for glutathione (GSH) synthesis results in increased metabolism of [gamma]-glutamyl cysteine to 5-oxoproline. We measured plasma 5-oxoproline as a metabolic indicator to address whether choline, via dimethylglycine, contributes physiologically relevant amounts of glycine in pregnancy. Blood was collected from healthy term pregnant women and their newborn infants at delivery (n = 46) and nonpregnant healthy women (n = 19) as a reference group. Plasma choline, betaine, dimethylglycine, homocysteine, methionine, and 5-oxoproline were quantified by HPLC-tandem MS. Plasma choline was 45% higher, but betaine was 63% lower and dimethylglycine was 28% lower in pregnant than nonpregnant women (P < 0.01). Higher white blood cell choline dehydrogenase messenger RNA levels in a random subset of pregnant (n = 8) than nonpregnant women (n = 7) (P < 0.01) suggest increased betaine and dimethylglycine turnover rather than decreased synthesis. Plasma choline, betaine, and dimethylglycine were higher (P < 0.001) in fetal plasma (36.4 [+ or -] 13, 29.4 [+ or -] 1.0, and 2.44 [+ or -] 0.12 [micro] mol/L, respectively) than maternal plasma (15.3 [+ or -] 0.42, 14.1 [+ or -] 0.6 and 1.81 [+ or -] 0.12 [micro] mol/L, respectively). Concentrations of 5-oxoproline and dimethylglycine were inversely (P < 0.05) correlated in maternal (Spearman rho = -0.35) and fetal plasma (Spearman rho = -0.32), suggesting that choline, via dimethylglycine, contributes glycine for GSH synthesis in human development. J. Nutr. 137: 2641-2646, 2007.

The liver produces plasma sex hormone-binding globulin (SHBG), which transports sex steroids and regulates their access to tissues. In overweight children and adults, low plasma SHBG levels are a biomarker of the metabolic syndrome and its associated pathologies. Here, we showed in transgenic mice and HepG2 hepatoblastoma cells that monosaccharides (glucose and fructose) reduce human SHBG production by hepatocytes. This occurred via a downregulation of hepatocyte nuclear factor-4[alpha] (HNF-4[alpha]) and replacement of HNF-4[alpha] by the chicken OVA upstream promoter-transcription factor 1 at a cis-element within the human SHBG promoter, coincident with repression of its transcriptional activity. The dose-dependent reduction of HNF-4[alpha] levels in HepG2 cells after treatment with glucose or fructose occurred in concert with parallel increases in cellular palmitate levels and could be mimicked by treatment with palmitoyl-CoA. Moreover, inhibition of lipogenesis prevented monosaccharide-induced downregulation of HNF-4[alpha] and reduced SHBG expression in HepG2 cells. Thus, monosaccharide-induced lipogenesis reduced hepatic HNF-4[alpha] levels, which in turn attenuated SHBG expression. This provides a biological explanation for why SHBG is a sensitive biomarker of the metabolic syndrome and the metabolic disturbances associated with increased fructose consumption., Introduction Body mass index is a major determinant of sex hormone-binding globulin (SHBG) concentrations in the blood of men and women (1-3). Low serum SHBG levels in overweight individuals are [...]

Although dietary fat has been associated with inflammation and cardiovascular diseases (CVD), most studies have focused on individuals with preexisting diseases. However, the role of dietary fatty acids on inflammatory pathways before the onset of any abnormality may be more relevant for identifying initiating factors and interventions for CVD prevention. We fed young male pigs one of three diets differing in n-6 and n-3 polyunsaturated fatty acids (PUFA) linoleic acid (LA, 18:2n-6) and ct-linolenic acid (ALA, 18:3n-3) for 30 days. Cardiac membrane phospholipid fatty acids, phospholipase [A.sub.2] ([PLA.sun.2]) isoform activities, and cyclooxygenase (COX)-1 and -2 and 5-1ipoxygenase (5-LO) expression were measured. The low PUFA diet (% energy, 1.2% LA+0.06% ALA) increased arachidonic acid (AA) and decreased eicosapentaenoic acid (EPA) in heart membranes and increased [Ca.sup.2+]-independent [iPLA.sub.2] activity, COX-2 expression, and activation of 5-LO. Increasing dietary ALA while keeping LA constant (1.4% LA + 1.2% ALA) decreased the heart membrane AA, increased EPA, and prevented proinflammatory enzyme activation. However, regardless of high ALA, high dietary LA (11.6% LA and 1.2% ALA) decreased EPA and led to a high heart membrane AA, and [Ca.sup.2+]-dependent [cPLA.sub.2] with a marked increase in nitrosative stress. Our results suggest that the potential cardiovascular benefit of ALA is achieved only when dietary LA is reduced concomitantly rather than fed with high LA diet. The increased nitrosative stress in the unstressed heart with high dietary LA suggests that biomarkers of nitrosative stress may offer a useful early marker of the effects of dietary fat on oxidative tissue stress. 5-lipoxygenase; phospholipase; oxidative stress; nitrotyrosine; arachidonic acid

Docosahexaenoic acid [DHA, 22:6(n-3)] is enriched in brain membrane phospholipids and is important to brain Development and function through its influence on neurite outgrowth and neurotransmitter secretion. Fusion of intracellular vesicles with the plasma membrane involving SNARE [soluble N-ethylmaleimide-sensitive fusion (NSF) protein attachment protein receptor] protein assembly, membrane fusion, and then disassembly are events common in membrane extension and neurotransmitter release. We determined whether feeding an (n-3) fatty acid-deficient diet, known to reduce brain phospholipid DHA, alters SNARE protein and SNARE complex expression or protein nitrosylation in the hippocampus of rats. Female rats were fed diets with 1.3 or 0.02% energy (n-3) [alpha]-linolenic acid from 2 wk before gestation then throughout gestation and lactation (n = 8/diet), and the male offspring were weaned to the maternal diet. Hippocampus phospholipid fatty acids and SNARE proteins were determined in male offspring at 90 d of age. Hippocampus phospholipid DHA was lower and (n-6) docosapentaenoic acid [DPA, 22:5(n-6)] was higher in the (n-3) fatty acid-deficient rats compared with the control group (P < 0.05). Multiplex Western blots using antibodies to syntaxin, synaptosome-associated protein of 25kDa (SNAP-25), and complexin II, showed higher ternary SNARE complexes but no differences in syntaxin, SNAP-25, or complex II expression in hippocampus of the (n-3) fatty acid-deficient rats compared with the control group (P < 0.05). S-nitrosylation of syntaxin was also significantly lower in the (n-3) fatty acid-deficient rats than in the control group. These studies suggest that altered SNARE complex binding or disassembly could be important in explaining the diverse cellular events associated with altered tissue DHA.

High linoleic acid (LA) intakes have been suggested to reduce [alpha]-linolenic acid [ALA, 18:3(n-3)] metabolism to eicosapentaenoic acid [EPA, 20:5(n-3)] and docosahexaenoic acid [DHA, 22:6(n-3)], and favor high arachidonic acid [ARA, 20:4(n-6)]. We used a randomized cross-over study with men (n = 22) to compare the effect of replacing vegetable oils high in LA with oils low in LA in foods, while maintaining constant ALA, for 4 wk each, on plasma (n-3) fatty acids. Nonvegetable sources of fat, except fish and seafoods, were unrestricted. We determined plasma phospholipid fatty acids at wk 0, 2, 4, 6, and 8, and trigtycerides, cholesterol, serum CRP, and IL-6, and platelet aggregation at wk 0, 4, and 8. LA and ALA intakes were 3.8 [+ or -] 0.12% and 1.0 [+ or -] 0.05%, and 10.5 [+ or -] 0.53% and 1.1 [+ or -] 0.06% energy with LA:ALA ratios of 4:0 and 10:1 during the low and high LA diets, respectively. The plasma phospholipid LA was higher and EPA was lower during the high than during the low LA diet period (P < 0.001), but DHA declined over the 8-wk period (r = -0.425, P < 0.001 ). The plasma phospholipid ARA:EPA ratios were (mean [+ or -] SEM) 20.7 [+ or -] 1.52 and 12.9 [+ or -] 1.01 after 4 wk consuming the high or low LA diets, respectively (P < 0.001); LA was inversely associated with EPA (r = -0.729, P < 0.001) but positiv ely associated with ARA: EPA (r= 0.432, P < 0.001 ). LA intake did not influence ALA, ARA, DPA, DHA, or total, LDL or HDL cholesterol, CRP or IL-6, or platelet aggregation. In conclusion, high LA intakes decrease plasma phospholipid EPA and increase the ARA:EPA ratio, but do not favor higher ARA. J. Nutr. 137: 945-952, 2007.

The (n-3) fatty acids are essential dietary nutrients, and one of their important roles is providing docosahexaenoic acid [22:6(n-3)] (DHA) for growth and function of nervous tissue. Reduced DHA is associated with impairments in cognitive and behavioral performance, effects which are particularly important during brain development. Recent studies suggest that DHA functions in neurogenesis, neurotransmission, and protection against oxidative stress. These functions relate to the roles of DHA within the hydrophobic core of neural membranes and effects of unesterified DHA. Reviewed here are some of the recent studies that have begun to elucidate the role of DHA in brain development and function. A better understanding of development and age-specific changes in DHA transfer and function in the developing brain may provide important insight into the role of DHA in developmental disorders in infants and children, as well as at other stages of the lifespan.

Trans fatty acids in human milk have raised concerns because of possible adverse effects on infant growth and development. Analyses of human milk in the late 1990s in Canada showed high amounts of trans fatty acids from partially hydrogenated oils. Canada introduced labeling of trans fatty acids on retail foods in 2003. We analyzed trans and cis unsaturated and saturated fatty acids in human milk collected from 87 women in 2004-2006 and compared the levels to those in milk collected from 103 women in 1998 and analyzed using similar methods. The total trans fatty acids (mean [+ or -] SEM, g/100 g fatty acids) in human milk in Canada decreased significantly, from 7.1 [+ or -] 0.32 in 1998 to 6.2 [+ or -] 0.48, 5.3 [+ or -] 0.49, and 4.6 [+ or -] 0.32 over 3 consecutive 5-mo periods from November 2004 to January 2006. The milk total trans fatty acids were significantly and inversely related to 16:0, 18:2(n-6), 18:3(n-3), 20:4(n-6), 22:4(n-6), and 22:5(n-6) and positively related to 18:0 and conjugated linolenic acids (P < 0.05, n = 190). The estimated exposures of exclusively breast-fed infants to trans fatty acids decreased from a mean and 95th percentile intake of 2.0 and 4.4 g * [infant.sup.-1] * [d.sup.-1] in 1998 to 1.33 and 2.41 g * [infant.sup.-1] * [d.sup.-1], respectively, in late 2005. The estimated intake of the mothers was 4.0 (range 0.51-12.3) and 2.2 (0.56-7.65) g * [person.sup.-1] * [d.sup.-1] in 1998 and late 2005, respectively. Our studies show trans fatty acids have decreased in human milk in Canada, which suggests a concomitant decrease in trans fatty acid intake among lactating women and breast-fed infants.

Glucocorticoid therapy is often associated with impaired insulin sensitivity and cardiovascular disease. The present study was designed to evaluate cardiac fatty acid (FA) composition and metabolism following acute dexamethasone (Dex) treatment. Using the euglycemic hyperinsulinemic clamp, rats injected with Dex demonstrated a reduced glucose infusion rate. This whole body insulin resistance was also associated with a heart-specific increase in pyruvate dehydrogenase kinase 4 gene expression and a reduction in the rate of glucose oxidation. Dex treatment increased basal and postheparin plasma lipolytic activity. In the heart, palmitic and oleic acid levels were higher after 4 h of Dex and decreased to control (CON) levels within 8 h. Measurement of polyunsaturated FAs demonstrated a drop in linoleic and [gamma]-linolenic acid, with an increase in arachidonic acid (AA) after acute Dex injection. Tissue FA can be either oxidized or stored as triglyceride (TG). At 4 h, Dex augmented cardiac TG accumulation. However, this increase in tissue TG could not be maintained, such that at 8 h following Dex, TG declined to CON levels. AMP-activated protein kinase (AMPK) activation is known to promote FA oxidation through its control of acetyl-CoA carboxylase (ACC). Acute Dex promoted ACC phosphorylation, and increased cardiac palmitate oxidation, likely through its effects in increasing AMPK phosphorylation and total AMPK protein and gene expression. Whether these acute effects of Dex on FA oxidation, TG storage, and arachidonic acid accumulation can be translated into increased cardiovascular risk following chronic therapy has yet to be determined. palmitate oxidation; adenosine 5'-monophosphate-activated protein kinase; acetyl-coenzyme A carboxylase; lipoprotein lipase; polyunsaturated fatty acid doi:10.1152/ajpendo.00083.2006

Cystic fibrosis (CF) is associated with many clinical complications including steatosis for which the relation to defective CF transmembrane conductance regulator protein is unclear. Choline deficiency results in hepatic steatosis. Choline is the precursor of betaine, which donates methyl groups for remethylation of homocysteine to methionine and dimethylglycine. Previously, we have shown phospholipid malabsorption and increased plasma homocysteine in children with CF. In these studies we used normal phase HPLC with tandem mass spectrometry to determine plasma choline, betaine, and dimethylglycine in children with CF (n = 34) and healthy control children without CF (n = 15). Plasma choline, betaine, and dimethylglycine were significantly lower in children with CF (means [+ or -] SEM, 6.48 [+ or -] 0.35, 23.8 [+ or -] 1.49, 1.49 [+ or -] 0.13 [micro]mol/L, respectively) than in children without CF (8.98 [+ or -] 0.46, 37.3 [+ or -] 1.84, 3.01 [+ or -] 0.17 [micro]mol/L, respectively). Plasma choline (r= 0.373, P = 0.007) and betaine (r = 0.399, P = 0.005) were positively related to methionine, and choline was inversely related to homocysteine (r= -0.316, P = 0.03). Choline, betaine, and dimethylglycine were all significantly and positively related to the plasma S-adenosylmethionine:S-adenosylhomocysteine (SAM:SAH) ratio (r = 0.294, r = 0.377, r = 0.442, respectively; P < 0.05). The plasma choline:betaine and betaine:dimethylglycine ratios did not differ between the children with CF and the control children, suggesting no increase in betaine synthesis, or betaine-dependent remethylation of homocysteine. These studies suggest that choline depletion may contribute to increased homocysteine in children with CF. Choline depletion and altered thiol metabolism may contribute to the clinical complications associated with CF.

Docosahexaenoic acid [22:6(n-3)] is enriched in brain membrane phospholipids and essential for brain function. Neurogenesis during embryonic and fetal development requires synthesis of large amounts of membrane phospholipid. We determined whether dietary (n-3) fatty acid deficiency during gestation alters neurogenesis in the embryonic rat brain. Female rats were fed diets with 1.3% energy [(n-3) control] or 0.02% energy [(n-3) deficient], from [alpha]-linolenic acid [18:3(n-3)], beginning 2 wk before gestation. Morphometric analyses were performed on embryonic day 19 to measure the mean thickness of the neuroepithelial proliferative zones corresponding to the cerebral cortex (ventricular and subventricular zones) and dentate gyrus (primary dentate neuroepithelium), and the thickness of the cortical plate and sectional area of the dentate gyrus. Phospholipids and fatty acids were determined by HPLC and GLC. Docosahexaenoic acid was 55-65% lower and (n-6) docosapentaenoic acid [22:5(n-6)] was 150-225% higher in brain phospholipids at embryonic day 19 in the (n-3) deficient (n 6 litters) than in the control (n = 5 litters) group. The mean thickness of the cortical plate and mean sectional area of the primordial dentate gyrus were 26 and 48% lower, respectively, and the mean thicknesses of the cortical ventricular zone and the primary dentate neuroepithelium were 110 and 70% higher, respectively, in the (n-3) deficient than in the control embryonic day 19 embryos. These studies demonstrate that (n-3) fatty acid deficiency alters neurogenesis in the embryonic rat brain, which could be explained by delay or inhibition of normal development. KEY WORDS: * (n-3) fatty acids * docosahexaenoic acid * neurogenesis * cerebral cortex * dentate gyrus

We investigated whether maternal fat intake alters amniotic fluid and fetal intestine phospholipid n-6 and n-3 fatty acids. Female rats were fed a 20% by weight diet from fat with 20% linoleic acid (LA; 18:2n-6) and 8% [alpha]-linolenic acid (ALA; 18:3n-3) (control diet, n = 8) or 72% LA and 0.2% ALA (n-3 deficient diet, n = 7) from 2 wk before and then throughout gestation. Amniotic fluid and fetal intestine phospholipid fatty acids were analyzed at day 19 gestation using HPLC and gas-liquid chromotography. Amniotic fluid had significantly lower docosahexaenoic acid (DHA; 22:6n-3) and higher docosapentaenoic acid (DPA; 22:5n-6) levels in the n-3-deficient group than in the control group (DHA: 1.29 [+ or -] 0.10 and 6.29 [+ or -] 0.33 g/100 g fatty acid; DPA: 4.01 [+ or -] 0.35 and 0.73 [+ or -] 0.15 g/100 g fatty acid, respectively); these differences in DHA and DPA were present in amniotic fluid cholesterol esters and phosphatidylcholine (PC). Fetal intestines in the n-3-deficient group had significantly higher LA, arachidonic acid (20:4n-6), and DPA levels; lower eicosapentaenoic acid (EPA; 20:5n-3) and DHA levels in PC; and significantly higher DPA and lower EPA and DHA levels in phosphatidylethanolamine (PE) than in the control group; the n-6-to-n-3 fatty acid ratio was 4.9 [+ or -] 0.2 and 32.2 [+ or -] 2.1 in PC and 2.4 [+ or -] 0.03 and 17.1 [+ or -] 0.21 in PE in n-3-deficient and control group intestines, respectively. We demonstrate that maternal dietary fat influences amniotic fluid and fetal intestinal membrane structural lipid essential fatty acids. Maternal dietary fat can influence tissue composition by manipulation of amniotic fluid that is swallowed by the fetus or by transport across the placenta. fetal intestinal development; docosahexaenoic acid

Increasing evidence suggests that fetal and neonatal nutrition impacts later health. Aims of the present study were to determine the effect of maternal dietary fat composition on intestinal phospholipid fatty acids and responsiveness to experimental colitis in suckling rat pups. Female rats were fed isocaloric diets varying only in fat composition throughout gestation and lactation. The oils used were high (8%) in n-3 [canola oil (18:3n-3)], n-6 (72%) [safflower oil (18:2n-6)], or n-9 (78%) [high oleic acid safflower oil (18:1n-9)] fatty acids, n = 6/group. Colitis was induced on postnatal day 15 by intrarectal 2,4-dinitrobenzene sulfonic acid (DNBS) administration with vehicle (50% ethanol) and procedure (0.9% saline) controls. Jejunal and colonic phospholipids and milk fatty acids were determined. The distal colon was assessed for macroscopic damage, histology, and MPO activity. The 18:2n-6 maternal diet increased n-6 fatty acids, whereas the 18:3n-3 diet increased n-3 fatty acids in milk and pup jejunal and colonic phospholipids. Maternal diet, milk, and pup intestinal n-6-to-n-3 fatty acid ratios increased significantly in order: high 18:3n-3 < high 18:1n-9 < high 18:2n-6. DNBS administration in pups in the high 18:2n-6 group led to severe colitis with higher colonic damage scores and MPO activity than in the 18:1n-9 and 18:3n-3 groups. High maternal dietary 18:3n-3 intake was associated with colonic damage scores and MPO activity, which were not significantly different from ethanol controls. We demonstrate that maternal dietary fat influences the composition of intestinal lipids and responsiveness to experimental colitis in nursing offspring. maternal diet; lipids; suckling pups; inflammatory bowel disease

Given the importance of lipoprotein lipase (LPL) in cardiac and vascular pathology, the objective of the present study was to investigate whether the [beta]-agonist isoproterenol (Iso) influences cardiac LPL. Incubation of quiescent cardiomyocytes with Iso for 60 min had no effect on basal, intracellular, or heparin-releasable (HR)-LPL activity. Similarly, Iso did not change HR-LPL in Langendorff isolated hearts that do not beat against an afterload. In the intact animal. LPL activity at the vascular lumen increased significantly in the Iso-treated group, together with a substantial increase in rate-pressure product. This LPL increase was likely via mechanisms regulated by activation of AMP-activated protein kinase (AMPK) and inactivation of acetyl-CoA carboxylase (AC[C.sub.280]). In glucose-perfused hearts, simply switching from Langendorff to the isolated working heart (that beats against an afterload) induced increases in AMPK and AC[C.sub.280] phosphorylation and enhanced HR-LPL activity. Provision of insulin and albumin-bound palmitic acid to the working heart was able to reverse these effects. In these hearts, introduction of Iso to the buffer perfusate duplicated the effects seen when this [beta]-agonist was given in vivo. Our data suggest that Iso can influence HR-LPL only during conditions of increased workload, mechanical performance and excessive energy expenditure, and likely in an AMPK-dependent manner. isoproterenol; acetyl-coenzyme A carboxylase; cardiomyocyte; Langendorff heart; working heart; adenosine 3',5'-monophosphate-activated protein kinase; lipoprotein lipase