Serum Vitamins A and E at Mid-Pregnancy and Their Relationships with Both Maternal and Cord Blood Antioxidant Status and Perinatal Conditions: The NELA Cohort.

INTRODUCTION: Most of the pregnant women do not achieve the recommended dietary intake of vitamins A and E. These vitamins may counteract oxidative stress involved in some adverse perinatal outcomes. We aimed to assess the associations between maternal vitamin A and E at mid-pregnancy with both maternal and fetal outcomes and to identify possible early biomarkers during pregnancy to predict and prevent oxidative stress in the offspring. METHODS: Data on dietary and serum levels of vitamins A and E were collected from 544 pregnant women from the Nutrition in Early Life and Asthma (NELA) study, a prospective mother-child cohort set up in Spain. RESULTS: There were large discrepancies between low dietary vitamin E intake (78% of the mothers) and low serum vitamin E levels (3%) at 24 weeks of gestation. Maternal serum vitamins A and E at mid-pregnancy were associated with higher antioxidant status not only in the mother at this time point (lower hydroperoxides and higher total antioxidant activity [TAA]) but also with the newborn at birth (higher TAA). Gestational diabetes mellitus (GDM) was negatively associated with maternal serum vitamin A (OR: 0.95 CI: 0.91-0.99, p = 0.009) at mid-pregnancy. Nevertheless, we could not detect any association between GDM and oxidative stress parameters. CONCLUSIONS: In conclusion, maternal vitamin A and E serum levels may be used as an early potential biomarker of antioxidant status of the neonate at birth. Control of these vitamins during pregnancy could help avoid morbid conditions in the newborn caused by oxidative stress in GDM pregnancies.

Natural Vitamin E Supplementation during Pregnancy in Rats Increases RRR-α-Tocopherol Stereoisomer Proportion and Enhances Fetal Antioxidant Capacity, Compared to Synthetic Vitamin E Administration.

INTRODUCTION: Low dietary intake of vitamin E is a global public health issue. RRR-α-tocopherol (RRR-αT) is the only naturally occurring vitamin E stereoisomer, but the equimolecular mixture of all eight stereoisomers, synthetic vitamin E (S-αT), is commonly consumed. The objective of this study was to evaluate bioavailability and antioxidant activity of RRR-αT versus S-αT, in both mother and fetus, after maternal supplementation during pregnancy. METHODS: Female rats (7 weeks of age) received a modified AIN-93G diet supplemented with 75 IU/kg of RRR-αT (NVE, n = 20) or S-αT (SVE, n = 17). At delivery, the levels of αT, stereoisomer distribution, and antioxidant capacity were analyzed in maternal and fetal plasma. RESULTS: NVE administration significantly increased the proportion of RRR-αT stereoisomer in maternal and fetal plasma. The percentage of RRR-αT increased from 32.76% to 88.33% in maternal plasma, and 35.25% to 97.94% in fetal plasma, in the NVE group compared to SVE. Fetal plasma from the NVE group was found to have higher total antioxidant capacity compared to SVE. Lastly, fetal plasma RRR-αT stereoisomer percentage was positively associated with expression levels of scavenger receptor class B type 1 (SR-B1) in the placenta. CONCLUSIONS: Both natural and synthetic sources of vitamin E showed similar bioavailability. Still, NVE supplementation increased the proportion of RRR-αT and promoted higher antioxidant activity in fetal plasma at birth. Placental SR-B1 might be involved in the stereoselective transfer of RRR-αT stereoisomer across the placenta and may improve αT bioactivity in the fetus.

Vitamin B12 Induces Hepatic Fatty Infiltration through Altered Fatty Acid Metabolism.

BACKGROUND/AIMS: Rise in global incidence of obesity impacts metabolic health. Evidence from human and animal models show association of vitamin B12 (B12) deficiency with elevated BMI and lipids. Human adipocytes demonstrated dysregulation of lipogenesis by low B12 via hypomethylation and altered microRNAs. It is known de novo hepatic lipogenesis plays a key role towards dyslipidaemia, however, whether low B12 affects hepatic metabolism of lipids is not explored. METHODS: HepG2 was cultured in B12-deficient EMEM medium and seeded in different B12 media: 500nM(control), 1000pM(1nM), 100pM and 25pM(low) B12. Lipid droplets were examined by Oil Red O (ORO) staining using microscopy and then quantified by elution assay. Gene expression were assessed with real-time quantitative polymerase chain reaction (qRT-PCR) and intracellular triglycerides were quantified using commercial kit (Abcam, UK) and radiochemical assay. Fatty acid composition was measured by gas chromatography and mitochondrial function by seahorse XF24 flux assay. RESULTS: HepG2 cells in low B12 had more lipid droplets that were intensely stained with ORO compared with control. The total intracellular triglyceride and incorporation of radio-labelled-fatty acid in triglyceride synthesis were increased. Expression of genes regulating fatty acid, triglyceride and cholesterol biosynthesis were upregulated. Absolute concentrations of total fatty acids, saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), trans-fatty acids and individual even-chain and odd-chain fatty acids were significantly increased. Also, low B12 impaired fatty acid oxidation and mitochondrial functional integrity in HepG2 compared with control. CONCLUSION: Our data provide novel evidence that low B12 increases fatty acid synthesis and levels of individual fatty acids, and decreases fatty acid oxidation and mitochondrial respiration, thus resulting in dysregulation of lipid metabolism in HepG2. This highlights the potential significance of de novo lipogenesis and warrants possible epigenetic mechanisms of low B12.

Environmental Exposure during Pregnancy: Influence on Prenatal Development and Early Life: A Comprehensive Review.

Preconception and prenatal exposure to environmental contaminants may affect future health. Pregnancy and early life are critical sensitive windows of susceptibility. The aim of this review was to summarize current evidence on the toxic effects of environment exposure during pregnancy, the neonatal period, and childhood. Alcohol use is related to foetal alcohol spectrum disorders, foetal alcohol syndrome being its most extreme form. Smoking is associated with placental abnormalities, preterm birth, stillbirth, or impaired growth and development, as well as with intellectual impairment, obesity, and cardiovascular diseases later in life. Negative birth outcomes have been linked to the use of drugs of abuse. Pregnant and lactating women are exposed to endocrine-disrupting chemicals and heavy metals present in foodstuffs, which may alter hormones in the body. Prenatal exposure to these compounds has been associated with pre-eclampsia and intrauterine growth restriction, preterm birth, and thyroid function. Metals can accumulate in the placenta, causing foetal growth restriction. Evidence on the effects of air pollutants on pregnancy is constantly growing, for example, preterm birth, foetal growth restriction, increased uterine vascular resistance, impaired placental vascularization, increased gestational diabetes, and reduced telomere length. The advantages of breastfeeding outweigh any risks from contaminants. However, it is important to assess health outcomes of toxic exposures via breastfeeding. Initial studies suggest an association between pre-eclampsia and environmental noise, particularly with early-onset pre-eclampsia. There is rising evidence of the negative effects of environmental contaminants following exposure during pregnancy and breastfeeding, which should be considered a major public health issue.

Placental lipid droplet composition: Effect of a lifestyle intervention (UPBEAT) in obese pregnant women.

Maternal obesity is associated with adverse outcomes. Placental lipid droplets (LD) have been implicated in maternal-fetal lipid transfer but it is not known whether placental LD fat composition is modifiable. We evaluated the effects of a diet and physical activity intervention in obese pregnant women compared to routine antenatal care (UPBEAT study) on placental LD composition. LD were isolated by ultracentrifugation. Total FAs and phospholipids (phosphatidylcholines, PCs; sphingomyelins, SMs and lyso-phosphatidylcholines, Lyso-PCs) were analyzed by LC-MS/MS. Placenta MFSD2a expression was assessed by western blot. Placental LDs from obese women were comprised of predominantly saturated and monounsaturated FAs. TG and Chol composition was similar between intervention (n = 20) and control (n = 23) groups. PCs containing dihomo-ɣ-linolenic acid in LD were positively associated with gestational weight gain (P < 0.007), and lowered by the intervention. In the whole sample, PCs carrying DHA and arachidonic acid were inversely associated with placental weight. Placenta MFSD2a expression was associated with DHA cord blood metabolites and relationships were observed between LD lipids, especially DHA carrying species, and cord blood metabolites. We describe placenta LD composition for the first time and demonstrate modest, potentially beneficial effects of a lifestyle intervention on LD FAs in obese pregnant women.

Maternal and Foetal Health Implications of Vitamin D Status during Pregnancy.

BACKGROUND: To what extent does the circulating 25-hydroxyvitamin D (25[OH]D) concentration help to meet the physiological needs of humans is an ongoing subject of debate. Remaining unexposed to the sun to reduce melanoma cancer risk, current lifestyle with less out door activities, and increasing obesity rates, which in turn increases the storage of vitamin D in the adipose tissue, are presumably factors that contribute to the substantial upsurge in the prevalence of vitamin D deficiency in humans. Since evidence is lacking regarding the appropriate cut-off points to define vitamin D status during pregnancy, references used to establish the intake recommendations and vitamin D content of prenatal vitamin supplements are quite conservative. SUMMARY: The foetus depends fully on maternal 25(OH)D supply. 25(OH)D readily crosses the placenta and it is activated into 1,25(OH)2D by foetal kidneys. Moreover, 1,25(OH)2D can also be synthesized within the placenta to regulate placental metabolism. The importance of vitamin D during pregnancy for maintaining maternal calcium homeostasis and therefore for foetal bone development is well recognized; major discussions are in progress regarding the potential maternal detrimental effects on pregnancy outcomes, foetal development, and the long-term health of children. Interventional studies have also evaluated the effect of vitamin D for reduction on preterm birth and asthma programming. Key Messages: Clinically, by understanding the effects of vitamin D on perinatal outcomes, we could individualize antenatal counselling regarding vitamin D supplementation to ensure vitamin D repletion without increasing the risk of foetal hypercalcemia.

Placental MFSD2a transporter is related to decreased DHA in cord blood of women with treated gestational diabetes.

BACKGROUND & AIMS: Maternal-fetal transfer of docosahexaenoic acid (DHA) is impaired by gestational diabetes mellitus (GDM), but the underlying mechanisms are still unknown. MFSD2a was recently recognized as a lyso-phospholipid (lyso-PL) transporter that facilitates DHA accretion in brain. The role of this transporter in placenta is uncertain. We evaluated effects of GDM and its treatment (diet or insulin) on phospholipid species, fatty acid profile in women, cord blood and placental fatty acid carriers. METHODS: Prospective observational study of pregnant women recruited in the third trimester (25 controls, 23 GDM-diet, 20 GDM-insulin). Fetal ultrasound was performed at gestational week 38. At delivery, maternal and neonatal anthropometry was performed, and fatty acids in total lipids and phospholipid species were analyzed in placenta, maternal and venous cord blood. Western-blot analyses were performed for placental fatty acid carriers. RESULTS: Fetal abdominal circumference z-score at 38 weeks tended to higher values in GDM (P = 0.071), pointing toward higher fetal fat accretion in these babies. DHA percentage in cord serum total lipids (P = 0.029) and lyso-PL (P = 0.169) were reduced in GDM. Placental MFSD2a was reduced in both GDM groups and was positively correlated to DHA values in cord serum total lipids (r = 0.388, P = 0.003). Among established placental lipid carriers, only FATP4 was correlated to DHA concentration in placental lyso-PL. In all compartments, DHA percentage was inversely correlated to fetal abdominal circumference. CONCLUSIONS: In offspring of women with GDM treated either with diet or insulin, higher fetal fat accretion and lower placental MFSD2a contribute to reduce DHA availability. Lyso-PL appear to contribute to materno-fetal DHA transport.

A gene variant in the transcription factor 7-like 2 (TCF7L2) is associated with an increased risk of gestational diabetes mellitus.

OBJECTIVE: Adipokines play an important role in the pathogenesis of insulin resistance during pregnancy. We studied the association of genetic variants linked with type 2 diabetes in gestational diabetes mellitus (GDM) subjects and its influence on maternal adipokines. STUDY DESIGN: We recruited 25 healthy pregnant women (Controls) and 45 women with GDM at 24-28 weeks of gestation. Maternal blood samples were collected at recruitment and delivery. Adipokines were determined at both sampling times. Genomic DNA was extracted from recruitment samples and FTO rs9939609, TCF7L2 rs4506565, rs7901695, rs12243326, rs12255372 and rs7903146, INSIG2 rs7566605, SREBF1 rs114001633, rs45535737 and rs12941356 and FATP4 rs2003560 genotyped. RESULTS: Serum adiponectin was significantly lower in GDM than Controls at recruitment and showed a similar trend at delivery (p=0.060). In contrast, resistin tended to higher levels in GDM only at recruitment. TCF7L2 rs4506565 (OR=2.31, 95% CI: 1.97-5.01; p=0.031) and FTO rs9939609 (OR=2.17, 95% CI: 1.07-4.41; p=0.039) were associated with GDM risk. Women carrying the T allele of TCF7L2 rs4506565 had increases in plasma resistin of 9.38 µg/L (95% CI 1.39-17.37; p=0.022) per allele; this association remained significant after adjusting for pre-gestational body weight. CONCLUSION: TCF7L2 rs4506565 variant (T/T) is associated with increased risk of GDM and plasma resistin concentrations in women with GDM.

Effect of the consumption of a fruit and vegetable soup with high in vitro carotenoid bioaccessibility on serum carotenoid concentrations and markers of oxidative stress in young men.

AIM: To evaluate the effect of the daily intake of a fruit & vegetable soup with high in vitro bioaccessibility of carotenoids on ß-carotene and lycopene serum concentrations. METHODS: Fourteen healthy young men (24 ± 1 years) received 300 mL/day of a carrot, tomato, and broccoli soup, containing 3.9 mg ß-carotene and 4 mg lycopene, for 4 weeks followed by a 4-week washout period. The serum carotenoid response and oxidative markers were analyzed after 3 and 4 weeks of soup consumption and after a 4-week washout. RESULTS: The in vitro bioaccessibility of ß-carotene and lycopene was 55 and 43%, respectively, in the soup. Serum ß-carotene concentrations were significantly higher than baseline (0.33 ± 0.05 µmol/L) after 3 weeks (0.69 ± 0.06 µmol/L) and 4 weeks (0.78 ± 0.10 µmol/L) of soup consumption (P < 0.001). Serum lycopene was also significantly higher compared with baseline levels (0.26 ± 0.08-0.56 ± 0.04 µmol/L and 0.60 ± 0.04 µmol/L, after 3 and 4 weeks, respectively) (P < 0.001). Although the highest concentration of both carotenoids was found after 4 weeks, the levels were not statistically different from the levels at 3 weeks. A 4-week washout significantly decreased serum carotenoid concentrations, although only ß-carotene returned to baseline. Glutathione peroxidase (GPx) increased significantly after soup supplementation compared with baseline, while superoxide dismutase was significantly lower only after 3 weeks. Glutathione reductase, lipid, protein, and DNA oxidative markers remained unchanged. CONCLUSIONS: The soup contributed to increasing the concentration of each carotenoid by more than 100% after 3 and 4 weeks of consumption, the maximum increase being observed after 4 weeks. Oxidative markers did not show any variation except for GPx. Serum lycopene half-life was longer than that of ß-carotene, which may be important for studies evaluating both carotenoids.

Protective effect of white tea extract against acute oxidative injury caused by adriamycin in different tissues.

Adriamycin (ADR) is an anticancer agent that increases oxidative stress in cells. We evaluated the protective effect of the long term consumption of white tea at two different doses against this drug. For this purpose rats were given distilled water (controls), 0.15 mg (Dose 1) or 0.45 mg (Dose 2) of solid tea extract/kg body weight for 12 months. All the animals received an injection of ADR, except half of the control group, which were given an injection of saline solution. This gave four experimental groups: Control (C), C+ADR, Dose 1+ADR, and Dose 2+ADR. The antioxidant activity (in liver, heart and brain microsomes) was analysed. White tea consumption for 12 months, at a non-pharmacological dose, reversed the oxidative damage caused by ADR, on both protein and lipid levels in all three organs. The heart recovered its antioxidant activity only at the highest dose of tea.

White tea consumption slightly reduces iron absorption but not growth, food efficiency, protein utilization, or calcium, phosphorus, magnesium, and zinc absorption in rats.

We investigated the antinutritional effect of white tea extract (0, 15, and 45 mg of the tea solid extract per kilogram body weight) incorporated in the drinking water of rats for 3 and 30 days. Gender-based differences were found for all these variables, except apparent protein digestibility and the apparent absorption of calcium, phosphorus, and iron. White tea extract consumption did not significantly change body weight gain, food intake, food efficiency, protein efficiency ratio, apparent protein digestibility, nitrogen balance, or the apparent absorption of calcium, phosphorus, magnesium, and zinc. Nevertheless, the apparent absorption of iron was slightly (15-18%) but significantly (P<0.05) lower in rats that consumed white tea at the highest dose compared with the control groups at both 3 and 30 days. Our results suggest that the usual consumption of white tea is safe, although its effect on long-term iron absorption at high doses warrants more detailed investigation.

Dehydroepiandrosterone-sulfate modifies human fatty acid composition of different adipose tissue depots.

BACKGROUND: Dehydroepiandrosterone-sulfate (DHEA-S) has been described as a protector agent against obesity-related pathologies, although the mechanism of action is still unknown. We have shown that DHEA-S acts on adipose tissue (AT), altering the fatty acid (FA) profile in rodents. Thus, we could hypothesize that some of the beneficial effects shown by DHEA-S in humans are related to a modification of the human AT-FA profile. The present study examines this question and whether this effect is tissue-dependent. METHODS: Paired visceral and subcutaneous AT biopsies were obtained from 20 patients who had undergone bariatric surgery. These samples were subjected to primary adipose culture and incubated for 24 h with 1 µM DHEA-S. The FA profile of both control and treated samples were analyzed by gas chromatography. RESULTS: A reduction in total saturated fatty acids (SFA), the n-6 family of polyunsaturated fatty acids (PUFA) and the n-6/n-3 PUFA ratio was observed after DHEA-S treatment, whereas monounsaturated fatty acids (MUFA) increased. In addition, DHEA-S altered the percentage of several individual FA, decreasing palmitic acid and increasing vaccenic acid in both AT. All estimated desaturase activity ratios slightly increased after DHEA-S treatment, although only the increase of delta-6-desaturase index in both depots reached statistical significance. No depot-specific action of DHEA-S was found between subcutaneous and visceral AT. CONCLUSIONS: In vitro, DHEA-S modifies the AT-FA composition towards a better metabolic profile to a similar extent in the subcutaneous and visceral adipose depots, in both of which a decrease in SFA and increased MUFA are observed after treatment. This effect could help to explain the beneficial effects attributed to DHEA-S. Further studies, however, are required to determine whether the effect of DHEA-S on adipose tissue in vitro is conserved in vivo.

Cell-based assay to quantify the antioxidant effect of food-derived carotenoids enriched in postprandial human chylomicrons.

We developed a new method to evaluate the antioxidant effect of food products in a biological system. The antioxidant status of HepG2 cells was quantified after incubation with postprandial human chylomicrons after the intake of vegetable products. Three subjects consumed in a meal a vegetable soup containing 8.4 mg of ß-carotene and 9 mg of lycopene. After 5 h, the subjects consumed a second meal without carotenoids. Blood samples were collected at basal time and every hour for 9 h. Chylomicrons were isolated from serum samples and used for both carotenoid quantification and HepG2 stimulation. Carotenoid in chylomicrons followed an inter-individual and bimodal carotenoid response. We demonstrated the antioxidant effect of postprandial chylomicrons in HepG2 at the time of maximum carotenoid concentration of chylomicrons with respect to basal time. This cell-based assay seems to be a useful method to evaluate the antioxidant effect of fruit and vegetable products in a biological system.

Relationship among adiponectin, adiponectin gene expression and fatty acids composition in morbidly obese patients.

BACKGROUND: The aim of this study was to examine the relationship between adiponectin plasma circulating levels and its gene expression in two abdominal fat depots (subcutaneous and visceral) with the fatty acid composition of plasma and adipose tissue in morbidly obese subjects. METHODS: 20 patients (10 women and 10 men) were selected. All were morbidly obese (BMI > or =40 kg/m2) and admitted for gastric surgery. Plasma samples and adipose tissue from both subcutaneous and visceral regions were obtained. Plasma adiponectin and adipose adiponectin expression were analyzed. RESULTS: Adiponectin mRNA expression in the subcutaneous tissue was significantly higher (P=0.048) than in visceral tissue. Circulating adiponectin values, were positively associated with the proportion of n-3 polyunsaturated fatty acids in plasma (r=0.62, P=0.002). The visceral depot showed greater statistical associations between adiponectin gene expression and fatty acids profile, being saturated fatty acids associated with a decrease (r=-0.68, P=0.015), whereas monounsaturated were related to an increase in this adipose region (r=0.67, P=0.017). CONCLUSIONS: We demonstrated significant associations between adipose tissue adiponectin gene expression and fatty acid composition. These associations were more evident in relation to the visceral depot, an adipose tissue region highly implicated in the metabolic syndrome.