High maternal folic acid intake around conception alters mouse blastocyst lineage allocation and expression of key developmental regulatory genes.

Folate, a cofactor for the supply of one-carbon groups, is required by epigenetic processes to regulate cell lineage determination during development. The intake of folic acid (FA), the synthetic form of folate, has increased significantly over the past decade, but the effects of high periconceptional FA intake on cell lineage determination in the early embryo remains unknown. Here, we investigated the effect of maternal high FA (HFA) intake on blastocyst development and expression of key regulatory genes. C57BL/6 adult female mice were fed either Control diet (1 mg FA) for 4 weeks before conception and during the preimplantation period (Con-Con); Control diet for 4 weeks preconception, followed by HFA (5 mg FA) diet during preimplantation (Con-HFA); or HFA diet for 4 weeks preconception and during preimplantation (HFA-HFA). At E3.5, blastocyst cell number, protein, and mRNA expression were measured. In HFA-HFA blastocysts, trophectoderm cell numbers and expression of CDX2, Oct-4, and Nanog were reduced compared with Con-Con blastocysts; Con-HFA blastocysts showed lower CDX2 and Oct-4 expression than Con-Con blastocysts. These findings suggest periconceptional HFA intake induces changes in key regulators of embryo morphogenesis with potential implications for subsequent development.

Differential DNA methylation of steatosis and non-alcoholic fatty liver disease in adolescence.

BACKGROUND AND AIMS: Epigenetic modifications are associated with hepatic fat accumulation and non-alcoholic fatty liver disease (NAFLD). However, few epigenetic modifications directly implicated in such processes have been identified during adolescence, a critical developmental window where physiological changes could influence future disease trajectory. To investigate the association between DNA methylation and NAFLD in adolescence, we undertook discovery and validation of novel methylation marks, alongside replication of previously reported marks. APPROACH AND RESULTS: We performed a DNA methylation epigenome-wide association study (EWAS) on DNA from whole blood from 707 Raine Study adolescents phenotyped for steatosis score and NAFLD by ultrasound at age 17. Next, we performed pyrosequencing validation of loci within the most 100 strongly associated differentially methylated CpG sites (dmCpGs) for which ≥ 2 probes per gene remained significant across four statistical models with a nominal p value < 0.007. EWAS identified dmCpGs related to three genes (ANK1, MIR10a, PTPRN2) that met our criteria for pyrosequencing. Of the dmCpGs and surrounding loci that were pyrosequenced (ANK1 n = 6, MIR10a n = 7, PTPRN2 n = 3), three dmCpGs in ANK1 and two in MIR10a were significantly associated with NAFLD in adolescence. After adjustment for waist circumference only dmCpGs in ANK1 remained significant. These ANK1 CpGs were also associated with γ-glutamyl transferase and alanine aminotransferase concentrations. Three of twenty-two differentially methylated dmCpGs previously associated with adult NAFLD were associated with NAFLD in adolescence (all adjusted p < 2.3 × 10-3). CONCLUSIONS: We identified novel DNA methylation loci associated with NAFLD and serum liver biochemistry markers during adolescence, implicating putative dmCpG/gene regulatory pathways and providing insights for future mechanistic studies.

Adiposity associated DNA methylation signatures in adolescents are related to leptin and perinatal factors.

Epigenetics links perinatal influences with later obesity. We identifed differentially methylated CpG (dmCpG) loci measured at 17 years associated with concurrent adiposity measures and examined whether these were associated with hsCRP, adipokines, and early life environmental factors. Genome-wide DNA methylation from 1192 Raine Study participants at 17 years, identified 29 dmCpGs (Bonferroni corrected p < 1.06E-07) associated with body mass index (BMI), 10 with waist circumference (WC) and 9 with subcutaneous fat thickness. DmCpGs within Ras Association (RalGDS/AF-6), Pleckstrin Homology Domains 1 (RAPH1), Musashi RNA-Binding Protein 2 (MSI2), and solute carrier family 25 member 10 (SLC25A10) are associated with both BMI and WC. Validation by pyrosequencing confirmed these associations and showed that MSI2 , SLC25A10 , and RAPH1 methylation was positively associated with serum leptin. These were  also associated with the early environment; MSI2 methylation (ß = 0.81, p = 0.0004) was associated with pregnancy maternal smoking, SLC25A10 (CpG2 ß = 0.12, p = 0.002) with pre- and early pregnancy BMI, and RAPH1 (ß = -1.49, p = 0.036) with gestational weight gain. Adjusting for perinatal factors, methylation of the dmCpGs within MSI2, RAPH1, and SLC25A10 independently predicted BMI, accounting for 24% of variance. MSI2 methylation was additionally associated with BMI over time (17 years old ß = 0.026, p = 0.0025; 20 years old ß = 0.027, p = 0.0029) and between generations (mother ß = 0.044, p = 7.5e-04). Overall findings suggest that DNA methylation in MSI2, RAPH1, and SLC25A10 in blood may be robust markers, mediating through early life factors.

Epigenetic changes in early life and future risk of obesity.

The rapid increase in incidence of obesity over the past two decades cannot be explained solely by genetic and adult lifestyle factors. There is now considerable evidence that the fetal and early postnatal environments also strongly influence the risk of developing obesity in later life. Initially, human studies showed that low birth weight was associated with an increased risk of obesity but increasingly there is evidence that overnutrition in the early life can also increase susceptibility to future obesity. These findings have now been replicated in animal models, which have shown that both maternal under- and overnutrition can induce persistent changes in gene expression and metabolism. The mechanism by which the maternal nutritional environment induces such changes is beginning to be understood and involves the altered epigenetic regulation of specific genes. In this review, we discuss the recent evidence that shows that early-life environment can induce altered epigenetic regulation leading to the induction of an altered phenotype. The demonstration of a role for altered epigenetic regulation of genes in the developmental induction of obesity opens the possibility that interventions, either through nutrition or specific drugs, may modify long-term obesity risk and combat this rapid rise in obesity.

Genetically modified plants are an alternative to oily fish for providing n-3 polyunsaturated fatty acids in the human diet: A summary of the findings of a Biotechnology and Biological Sciences Research Council funded project.

The n-3 polyunsaturated fatty acids (PUFA) present primarily in oily fish, namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are important components of cell membranes and that are needed for normal development and cell function. Humans have very limited capacity for EPA and DHA synthesis from α-linolenic acid and so they must be obtained pre-formed from the diet. However, perceived unpalatability of oily fish and fish oil concerns about contamination with environmental pollutants, dietary choices that exclude fish and animal products, and price limit the effectiveness of recommendations for EPA and DHA intakes. Moreover, marine sources of EPA and DHA are diminishing in the face of increasing demands. Therefore, an alternative source of EPA and DHA is needed that is broadly acceptable, can be upscaled and is sustainable. This review discusses these challenges and, using findings from recent nutritional trials, explains how they may be overcome by seed oils from transgenic plants engineered to produce EPA and DHA. Trials in healthy men and women assessed the acute uptake and appearance in blood over 8 hours of EPA and DHA from transgenic Camelina sativa compared to fish oil, and the incorporation of these PUFA into blood lipids after dietary supplementation. The findings showed that postprandial EPA and DHA incorporation into blood lipids and accumulation in plasma lipids after dietary supplementation was as good as that achieved with fish oil. The oil derived from this transgenic plant was well tolerated. This review also discusses the implications for human nutrition, marine ecology and agriculture.

Sex, but not maternal protein or folic acid intake, determines the fatty acid composition of hepatic phospholipids, but not of triacylglycerol, in adult rats.

The aim of the study was to investigate whether the protein and folic acid content of the maternal diet and the sex of the offspring alter the polyunsaturated fatty acid content of hepatic phospholipids and triacylglycerol (TAG). Pregnant rats were fed diets containing 18% or 9% protein with either 1 or 5mg/kg folic acid. Maternal diet did not alter hepatic lipid composition in the adult offspring. Data from each maternal dietary group were combined and reanalysed. The proportion of 18:0, 20:4n-6 and 22:6n-3 in liver phospholipids was higher in females than in males, while hepatic TAG composition did not differ between sexes. Delta5 Desaturase expression was higher in females than in males. Neither Delta5 nor Delta6 desaturase expression was related to polyunsaturated fatty acid concentrations. These results suggest that sex differences in liver phospholipid fatty acid composition may reflect primary differences in the specificity of phospholipid biosynthesis.

The effect of altering the 20:5n-3 and 22:6n-3 content of a meal on the postprandial incorporation of n-3 polyunsaturated fatty acids into plasma triacylglycerol and non-esterified fatty acids in humans.

Previous studies suggest that consuming meals containing large amounts of fish oil is associated with selective postprandial incorporation of 20:5n-3 and 22:6n-3 into plasma non-esterified fatty acids (NEFA). We investigated the effect of consuming meals containing different amounts of 20:5n-3 and 22:6n-3 comparable to dietary habits of western populations on the postprandial incorporation of 18:3n-3, 20:5n-3 and 22:6n-3 into plasma triacylglycerol (TAG) and NEFA over 6h in middle aged subjects. 20:5n-3 incorporation into plasma TAG was greater than 22:6n-3 irrespective of the test meal. Conversely, 22:6n-3 incorporation into plasma NEFA was greater than 20:5n-3, irrespective of the test meal. There was no effect of the amount of 20:5n-3+22:6n-3 in the test meal on the 18:3n-3 incorporation into plasma TAG or NEFA. These findings suggest differential metabolism of 20:5n-3 and 22:6n-3 in the postprandial period when consumed in amounts typical of western dietary habits.

Metabolism of alpha-linolenic acid in humans.

Alpha-linolenic acid (18:3n-3) is essential in the human diet, probably because it is the substrate for the synthesis of longer-chain, more unsaturated n-3 fatty acids eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3) which are required for tissue function. This article reviews the recent literature on 18:3n-3 metabolism in humans, including fatty acid beta-oxidation, recycling of carbon by fatty acid synthesis de novo and conversion to longer-chain polyunsaturated fatty acids (PUFA). In men, stable isotope tracer studies and studies in which volunteers increased their consumption of 18:3n-3 show conversion to 20:5n-3 and 22:5n-3, but limited conversion to 22:6n-3. However, conversion to 18:3n-3 to 20:5n-3 and 22:6n-3 is greater in women compared to men, due possibly to a regulatory effect of oestrogen, while partitioning of 18:3n-3 towards beta-oxidation and carbon recycling was lower than in men. These gender differences may be an important consideration in making dietary recommendations for n-3 PUFA intake.

Effect of maternal ethanol consumption during pregnancy on the phospholipid molecular species composition of fetal guinea-pig brain, liver and plasma.

The effect of maternal ethanol consumption during pregnancy upon accumulation of docosahexaenoic acid (22:6(n - 3)) into developing brain phospholipids was determined in a guinea-pig model of fetal alcohol syndrome. Feeding adult guinea-pigs 6 g/kg per day ethanol both before and throughout pregnancy was associated with decreased 22:6(n - 3) concentration in both fetal brain phosphatidylcholine (PC) and phosphatidylethanolamine (PE) at 40/68 days gestation and at term. Since adequate assimilation of 22:6(n - 3) into fetal brain is critical for optimal neuronal development, reduced accumulation of 22:6(n - 3) into phospholipids may be one important mechanism for ethanol-induced brain damage. Liver from ethanol-exposed fetuses contained significantly lower concentrations of both PC and PE 22:6(n - 3)-containing molecular species. However, there was no difference in plasma PC polyunsaturated fatty acid content in ethanol-exposed fetuses compared with controls. One possible explanation for impaired 22:6(n - 3) accumulation into ethanol-exposed fetal brain phospholipids may be the result of the action of inappropriate mechanisms which counteract ethanol-induced increased membrane fluidity by reducing the polyunsaturated fatty acid content of brain phospholipids.

Synthesis of phosphatidylcholine in guinea-pig fetal lung involves acyl remodelling and differential turnover of individual molecular species.

The mechanisms for accumulation of disaturated phosphatidylcholine (PC) molecular species in developing fetal guinea-pig lung during the period of surfactant synthesis, between day (d) 55 and term (d68), were determined by the incorporation of 50 mu Ci [methyl-14C]choline into lung PC in utero over 3 h. Comparison of the pattern of PC synthesis de novo with the composition of the total PC pool indicated that approx. 50% of the total PC16:0/16:0 was synthesized by acyl remodelling of PC16:0/18:2 by the actions of phospholipase A2 and acyltransferases. Acyl remodelling was established before the onset of surfactant synthesis (d55) and so was not specific for this process. Between d55 and term the concentration of lung PC increased significantly. Conversely, the incorporation of [14C]choline into lung tissue and the rate of PC synthesis decreased over this period. Calculation of turnover times of lung PC species suggested that the increase in lung disaturated PC concentration during surfactant production might be due to a differential decrease in catabolism rather than increased PC synthesis.

Maternal diet as a modifier of offspring epigenetics.

There has been a substantial body of evidence, which has shown that genetic variation is an important determinant of disease risk. However, there is now increasing evidence that alterations in epigenetic processes also play a role in determining susceptibility to disease. Epigenetic processes, which include DNA methylation, histone modifications and non-coding RNAs play a central role in regulating gene expression, determining when and where a gene is expressed as well as the level of gene expression. The epigenome is highly sensitive to a variety of environmental factors, especially in early life. One factor that has been shown consistently to alter the epigenome is maternal diet. This review will focus on how maternal diet can modify the epigenome of the offspring, producing different phenotypes and altered disease susceptibilities.

Genome-wide methylation analysis identifies differentially methylated CpG loci associated with severe obesity in childhood.

Childhood obesity is a major public health issue. Here we investigated whether differential DNA methylation was associated with childhood obesity. We studied DNA methylation profiles in whole blood from 78 obese children (mean BMI Z-score: 2.6) and 71 age- and sex-matched controls (mean BMI Z-score: 0.1). DNA samples from obese and control groups were pooled and analyzed using the Infinium HumanMethylation450 BeadChip array. Comparison of the methylation profiles between obese and control subjects revealed 129 differentially methylated CpG (DMCpG) loci associated with 80 unique genes that had a greater than 10% difference in methylation (P-value < 0.05). The top pathways enriched among the DMCpGs included developmental processes, immune system regulation, regulation of cell signaling, and small GTPase-mediated signal transduction. The associations between the methylation of selected DMCpGs with childhood obesity were validated using sodium bisulfite pyrosequencing across loci within the FYN, PIWIL4, and TAOK3 genes in individual subjects. Three CpG loci within FYN were hypermethylated in obese individuals (all P < 0.01), while obesity was associated with lower methylation of CpG loci within PIWIL4 (P = 0.003) and TAOK3 (P = 0.001). After building logistic regression models, we determined that a 1% increase in methylation in TAOK3, multiplicatively decreased the odds of being obese by 0.91 (95% CI: 0.86 - 0.97), and an increase of 1% methylation in FYN CpG3, multiplicatively increased the odds of being obese by 1.03 (95% CI: 0.99 - 1.07). In conclusion, these findings provide evidence that childhood obesity is associated with specific DNA methylation changes in whole blood, which may have utility as biomarkers of obesity risk.

Mammalian secreted and cytosolic phospholipase A2 show different specificities for phospholipid molecular species.

Previous studies using phospholipid vesicles containing single molecular species have shown cytosolic phospholipase (85 kDa) (PL) A2 to possess a marked preference for arachidonic acid (20:4n-6)-containing species, while secreted PLA2 (14 kDa) exhibited little acyl chain selectivity. In this study, we have defined the molecular specificity of cytosolic PLA2 using phospholipid vesicles derived from rat liver which contain complex mixtures of molecular species. Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were isolated from rat liver by chloroform and methanol extraction, and solid-phase separation. PC and PE vesicles were hydrolysed by either human recombinant cytosolic or porcine pancreatic PLA2. Molecular species compositions were determined by reverse phase high performance liquid chromatography (HPLC) with post-column fluorescence derivitisation. HPLC analysis after limited hydrolysis demonstrated that the secreted phospholipase A2 showed no significant acyl chain specificity using these phospholipid mixtures. However, the cytosolic enzyme demonstrated a high degree of preference for arachidonic acid-containing species such that there was no hydrolysis of other molecular species. The extent of hydrolysis of PC16:0/20:4 was 1.4-fold greater (P < 0.05, n = 3) than PC18:0/20:4, while PE16:0/20:4 and PE18:0/20:4 were hydrolysed to a similar degree. Under these assay conditions, the cytosolic enzyme showed a preference for PE as compared with PC. This study confirms that cytosolic PLA2 is highly selective for sn-2 20:4n-6-containing phospholipid molecular species even when presented with a complex natural species mixture. This specificity is consistent with the cytosolic enzyme having a primary role in the process of arachidonic release within cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Conversion of alpha-linolenic acid to palmitic, palmitoleic, stearic and oleic acids in men and women.

The purpose of this study was to determine whether adult humans can recycle carbon from alpha-linolenic acid (18:3n-3) into saturated (SFA) and monounsaturated (MUFA) fatty acids. Six men and six women consumed 700 mg [U-13C]-18:3n-3. Blood was collected over 21 days and breath over 24h. [13C]-labelled SFA and MUFA were detected in plasma phosphatidylcholine (PC) and triacylglycerol (TAG). Total labelled fatty acid incorporation into SFA and MUFA was five- and 25-fold greater in PC than TAG in men and women, respectively. [13C]-16:0 was the major labelled fatty acid in both fractions. Total [13C] incorporation into SFA and MUFA was 20% greater in men than women, and related positively (r(2) = 0.35, P<0.05) to the fractional recovery of labelled 18:3n-3 as 13CO2 on breath. These results suggest that the extent of partitioning towards beta-oxidation and carbon recycling may regulate the availability of 18:3n-3 for conversion to longer-chain fatty acids.

Effect of meal sequence on postprandial lipid, glucose and insulin responses in young men.

OBJECTIVE: To investigate whether the postprandial changes in plasma triacylglycerol (TAG), nonesterified fatty acids (NEFA), glucose and insulin concentrations in young men were the same if an identical meal was fed at breakfast and lunch, and if the response to lunch was modified by consumption of breakfast. METHODS: In two trials (1 and 2) healthy subjects (age 22+/-1 y, body mass index 22+/-2 kg/m(2)) were fed the same mixed macronutrient meal at breakfast at 08:00 h and lunch at 14:00 h. In the third trial, no breakfast was fed and the overnight fast extended until lunch at 14:00 h. Addition of [1,1,1-(13)C]tripalmitin to one meal in each trial was used to distinguish between endogenous and meal-derived lipids. RESULTS: The postprandial changes in TAG, NEFA and glucose concentrations were similar in trials 1 and 2. The change in plasma total TAG concentration was about two fold less (P<0.05) after lunch compared to breakfast. Postprandial NEFA suppression was the same after breakfast and lunch. Glucose and insulin responses were significantly greater following lunch suggesting decreasing insulin sensitivity during the day. Consumption of breakfast did not alter the postprandial total TAG or NEFA responses after lunch. Measurement of [(13)C]palmitic acid concentration showed that handling of TAG and NEFA from the meal was the same after breakfast and lunch, and was not altered by consumption of breakfast. CONCLUSIONS: Overall, these data suggest that in young, healthy men regulation of plasma TAG from endogenous sources, principally VLDL, but not chylomicrons during the postprandial period leads to differences in the magnitude of lipaemic response when the same meal was consumed at breakfast or at lunch 6 h later.

The composition of individual molecular species of plasma phosphatidylcholine in human pregnancy.

The molecular species composition of plasma phosphatidylcholine (PC) was measured in sequential blood samples from 13 pregnant women from 16 weeks of gestation to delivery at term. The increased total plasma PC concentration at term was due solely to increased concentrations of individual species containing palmitate (16:0) rather than stearate (18:0) at the sn-1 position. The specific increase of PC16:0/22:6 concentration in mid-gestation suggests that adaptations to maternal hepatic PC metabolism may provide a mechanism to ensure adequate supply of 22:6(n-3) to the fetus. While cord plasma PC was comparable to liver PC composition from three stillborn term infants, the compositions of these tissues differed from maternal plasma PC, which contained significantly more PC16:0/18:2 and PC18:0/18:2. These results suggest that, although fetal acquisition of polyunsaturated fatty acids (PUFA) is dependent on the maternal lipid supply, the detailed composition of fetal plasma PC may be regulated largely by intrinsic fetal mechanisms such as placental and liver PC metabolism. Similarly, the specific alterations to maternal plasma PC composition in pregnancy, which we postulate are associated with the supply of PUFA to the fetus, were substantially independent of variations in maternal dietary lipid nutrition.

Pregnancy-associated adaptations to hepatic phosphatidylcholine biosynthesis in the guinea-pig.

Pregnancy is associated with increased phosphatidylcholine (PC) 16:0/22:6 and PC16:0/20:4 concentrations in rat liver and plasma, guinea-pig liver, and in plasma in women. These changes may be related to supply of polyunsaturated fatty acids (PUFA) to the fetus. For the rat, these adaptations to hepatic PC composition are regulated by modifications to synthesis de novo from choline. However, it is not known whether these adaptations are applicable to other species. Consequently, we have determined biochemical mechanisms for regulation of hepatic PC synthesis in the pregnant guinea pig. The PUFA content of guinea-pig liver PC synthesised de novo did not change significantly during pregnancy. [Methyl-14C]methionine incorporation into PC in vivo, however, showed increased PC16:0/22:6 and PC16:0/20:4 contents. [Methyl-14C]methionine incorporation into PC over 6 hr in vivo increased during early pregnancy, while PC synthesis de novo did not change. In contrast to the rat, modulation of PE N-methylation is a primary mechanism for regulating the PUFA content of hepatic PC in the pregnant guinea-pig. The use of distinct metabolic strategies to achieve comparable pregnancy-associated adaptations to hepatic PC composition between these animal species suggests both evolutionary convergence and a fundamental the role for PC16:0/22:6 and PC16:0/20:4 in PUFA metabolism during gestation.

Hepatic phospholipid molecular species in the guinea pig. Adaptations to pregnancy.

Incorporation of polyunsaturated fatty acids (PUFA), particularly 22:6n-3, into fetal brain at specific gestational ages is critical for development of normal brain function. We have studied adaptations to maternal liver phospholipid molecular species compositions that may be related to the supply of PUFA to fetal brain. The increment of 22:6n-3 in brain phosphatidylethanolamine (PE) was maximal at day 25 to day 35 of gestation, consistent with early prenatal development of guinea pig brain. At the same gestational ages, there was a transient increase in maternal liver concentration of 16:0/22:6 phosphatidylcholine (PC), which preceded the progressive increase in total PC concentration toward term (day 68). This effect was specific for the sn-1 16:0 species, as there was no significant increase in 18:0/22:6 PC concentration. These results are consistent with a specific role for 16:0/22:6 PC in the directed supply of 22:6n-3 from maternal liver to the fetus. Concentrations of all PE species in maternal liver decreased at day 25 and day 35 of gestation. The gradual accumulation of 22:6n-3 in fetal liver throughout gestation did not correlate with the pattern of acquisition of 22:6n-3 into fetal brain PE. Maternal plasma PC and cholesterol concentrations decreased dramatically by day 25 of gestation, and remained low until term. This hypolipidemia of pregnancy in the guinea pig may be due to increased lipase-mediated turnover of plasma lipoproteins and contrasts strongly with the well-characterized hyperlipidemia in human and rat gestation.

Phospholipid molecular species composition of developing fetal guinea pig brain.

Adequate accumulation of polyunsaturated essential fatty acids, in particular docosahexaenoic acid (22:6n-3), into membrane phospholipids is critical for optimal fetal brain development. This process is maximal during the period of rapid neurite outgrowth, neuritogenesis, which precedes the major growth phase, myelination. There is no information about differential changes during gestation to individual brain phospholipid molecular species which contain 22:6n-3. Such details of brain development would be concealed by total fatty acid analysis of isolated phospholipid classes. We have detailed phosphatidylcholine (PC) and phosphatidylethanolamine (PE) molecular species compositions in developing fetal guinea pig brain. Total brain PC concentration increased substantially between 40 and 68 (term) d of gestation, corresponding to myelination, while PE increased in a biphasic manner between 25-35 d, which was coincident with onset of neuritogenesis, and 40-68 d. Fetal brain development was accompanied by complex changes in the concentration of individual phospholipid molecular species. During early gestation (25-40 d) 22:6n-3 was enriched in both PC and PE sn-1 16:0 molecular species. However, between 40 d and term there was no further increase in brain PC 22:6n-3 content, while brain PE was significantly enriched in both PE18:1/22:6 and PE18:0/22:6. We hypothesize that accumulation of 22:6n-3 into sn-1 18:1 and 18:0 species represents establishment of a 22:6n-3-containing membrane PE pool which may be turned over more slowly than sn-1 16:0 species. Identification of specific changes in membrane phospholipids which are associated with defined events in brain development may provide a basis for assigning functional roles to individual molecular species.

Phospholipid composition of neonatal guinea pig liver and plasma: effect of postnatal food restriction.

Preterm guinea pigs were delivered on day 65 of gestation (term = 68 d) and were allowed either free or restricted access to food for the subsequent 48 h. Plasma phosphatidylcholine (PC) concentration increased postnatally from 190 (range 144-307) to 751 (426-1039) and 883 (758-977) microM for fed and starved pups, respectively. Plasma PC composition in both groups of pups was characterized by selective and equivalent relative increases to individual molecular species containing 18:0 at the sn-1 position. Hepatic PC concentration increased from 6.75 (5.41-8.20) to 8.65 (6.54-10.63) and 9.23 (8.18-10.17) mumol/g for fed and starved pups, respectively, and, under all conditions, hepatic PC molecular composition closely mirrored that of plasma PC. These results support the hypothesis that the molecular species composition of plasma PC for the guinea pig in the immediate postnatal period is determined largely by the composition of the hepatic PC pool destined for lipoprotein secretion. Hepatic PC composition and concentration of the starved neonatal guinea pig were maintained independently of any dietary nutrient intake, at the expense of mobilization of extra hepatic lipid reserves. While this adaptive mechanism has inherent limited survival potential in neonatal starvation, it has implications for studies measuring plasma phospholipid fatty acid compositions as biochemical markers of dietary fat intake in preterm infants.