Dietary gamma-linolenic acid dose-dependently modifies fatty acid composition and immune parameters in rats.

gamma-linolenic acid (GLA) has been reported to improve several inflammatory disorders through regulation of eicosanoid production. However, since GLA is a precursor of arachidonic acid, it may bring about increasing tissue arachidonic acid levels with subsequent pro-inflammatory events. To explore this possibility, we examined the effect of high-dose GLA acid on the fatty acid profile of immune cells, leukotriene B4 production by peritoneal exudate cells and immunoglobulin productivity of mesenteric lymph node lymphocytes of Sprague-Dawley rats. Male rats were fed 10% fat diets containing graded levels, 0, 20, 40 and 60% of GLA for 3 weeks. The results showed the distinction in activity of metabolizing GLA between immune cells and liver. Thus, in immune cells such as mesenteric lymph node and spleen lymphocytes and peritoneal exudate cells, more dihomo-gamma-linolenic acid was found than in the liver. Leukotriene B4 production by peritoneal exudate cells was significantly suppressed when fed the highest level of GLA suggesting a lower risk of allergic reaction. Moreover, immunoglobulin productivity in mesenteric lymph node lymphocytes was promoted by dietary GLA. The present study indicates that a high dose of GLA may exert anti-inflammatory effects through suppression of leukotriene B4 release and strengthening of gut immune system, thus ameliorating allergic reaction.     

Maternal dietary n-3 fatty acids alter immune cell fatty acid composition and leukotriene production in growing chicks

The effect of feeding different amounts of n-6 and n-3 fatty acids (FA) to hens on immune tissue FA composition and leukotriene production of hatched chicks was investigated. Hens were fed diets supplemented with either 3.0% sunflower oil (Diet I), 1.5% sunflower+1.5% fish oil (Diet II), or 3.0% fish oil (Diet III) for 46 days. The hatched chicks were fed a diet containing C18:3n-3, but devoid of longer chain n-6 and n-3 FA, for 21 days. Spleen docosahexaenoic acid (DHA) content was higher in chicks from hens fed Diet III (P<0.05). The bursa content of arachidonic acid was lower in chicks hatched from hens fed Diet III (P<0.05), and the ratio of n-6 to n-3 FA was significantly higher in bursa of chicks hatched to hens fed Diet I (P<0.05). Eicosapentaenoic acid (EPA) and DHA contents were higher in bursa of chicks hatched from hens fed Diet III (P<0.05). Thrombocytes from chicks hatched to hens fed Diet III produced the most leukotriene B(5) (LTB(5)). The ratio of LTB(5) to LTB(4) concentrations was also highest (P<0.05) in chicks hatched to hens fed Diet III. These results indicate that modulating maternal dietary n-6 and n-3 FA may alter leukotriene production in chicks, which could lead to less inflammatory-related disorders in poultry.     

Maternal renal insufficiency alters plasma composition and renal function in the fetal sheep

To determine the effects of chronic maternal renal insufficiency on fetal renal function, we studied nine fetuses whose mothers underwent subtotal nephrectomy at least 2 mo before mating (STNxF) and seven fetuses from intact ewes (IntF) (126-128 days of gestation, term 150 days). STNxF had lower hematocrit (P < 0.05), plasma chloride (P < 0.01), and creatinine levels (P < 0.01), and the length-to-width ratio of their kidneys was reduced (P < 0.05). They excreted twice as much urine (P < 0.05) and sodium (P < 0.01). Total (P = 0.01) and proximal fractional sodium reabsorptions (P < 0.05) were lower in STNxF; distal delivery of sodium (P < 0.05) and distal fractional sodium reabsorption (P < 0.05) were higher. They tended to have suppressed renin levels (P = 0.06). Infusions of amino acids (alanine, glycine, proline, and serine at 0.32 mmol/min for 1 h and 0.64 mmol/min for 2 h intravenously), known to stimulate renal blood flow and glomerular filtration rate in fetal sheep, did so in IntF (P < 0.01). Arterial pressure also increased (P < 0.01). These effects were not observed in STNxF. In summary, chronic maternal renal insufficiency was associated with profound alterations in fetal renal excretion of fluid and electrolytes and impaired renal hemodynamic and glomerular responses to amino acid infusion. Whether these marked changes in the renal function of fetuses carried by STNx ewes are associated with alterations in renal function in postnatal or adult life remains to be determined.     

The effect of diet upon the fatty acid composition of cranial and spinal nerve lipids.

The possible basal differences in lipid class and fatty acid composition between a cranial nerve (the trigeminal nerve) and two spinal nerves (the ulnar and sciatic nerves) as well as the effects of dietary lipids on the same nerves were studied. A basal (BD) and four experimental diets containing respectively hydrogenated coconut oil (HCO), grapestone oil (GSO), olive oil (OO) and linseed oil (LSO) were used. Trigeminal lipids fatty acid composition differs significantly from sciatic and ulnar ones in the percentages of 16:0, 16:1, 18:0, 18:2 n-6, 20:0, 20:1, 20:4 n-6, 24:0, 24:1 and 22:6 n-3. Also the proportions of triacylglycerols and free cholesterol strongly differ in trigeminal and spinal nerves whereas no significant difference was detected between ulnar and sciatic nerve lipids. Following the administration of the four experimental diets for 60 days, no significant change was observed in the fatty acid pattern of trigeminal lipids while the spinal ones showed a significant increase in the proportions of the fatty acids present in large quantities in the dietary oils used (i.e.: oleic acid in the OO samples). These changes are probably linked with the rapid metabolic turnover of triacylglycerols, present in larger amounts in spinal nerve lipids.     

Maternal and umbilical fatty acid status in relation to maternal diet

The aim of this study was to describe the dietary fat intake during pregnancy and to study the relationship between the intake of polyunsaturated fatty acids (PUFAs) and the fatty acid composition of maternal and umbilical plasma phospholipids (PLs) and cholesterol esters (CEs) at delivery. In addition, the contribution of food groups to the intake of total fat and fatty acids in the diet was quantified.Maternal and umbilical blood samples were collected at delivery from 30 healthy pregnant women. The women completed a food frequency questionnaire during the first and third trimesters. The total fat intake during pregnancy is 85 (SD 24) g/day. The mean intake of saturated fatty acids (SFAs) is 33.4 g/day, of monounsaturated fatty acids (MUFAs) 28.6 g/day and of PUFA 15.2 g/day. Major sources of fat, MUFA and PUFA are fats, oils and sauces. Major sources of SFA are meat and poultry followed by cheese and eggs. Meat and poultry contribute the most to the intake of 20:4n-6 whereas fish is the major source of 20:5n-3 (EPA) and 22:6n-3 (docosahexaenoic acid (DHA)) in the diet. Linoleic acid, EPA and DHA (w%) in PL of maternal plasma are positively related to the intake of these fatty acids during pregnancy. No association is found between the maternal intake of the two parent essential fatty acids (18:2n-6 and 18:3n-3) and their fraction in umbilical PL or CE. EPA and the sum of n-6 fatty acids (w%) in umbilical plasma PL are positively correlated with the dietary intake of these fatty acids.     

A low-protein diet during pregnancy alters glucose metabolism and insulin secretion

In pancreatic islets, glucose metabolism is a key process for insulin secretion, and pregnancy requires an increase in insulin secretion to compensate for the typical insulin resistance at the end of this period. Because a low-protein diet decreases insulin secretion, this type of diet could impair glucose homeostasis, leading to gestational diabetes. In pancreatic islets, we investigated GLUT2, glucokinase and hexokinase expression patterns as well as glucose uptake, utilization and oxidation rates. Adult control non-pregnant (CNP) and control pregnant (CP) rats were fed a normal protein diet (17%), whereas low-protein non-pregnant (LPNP) and low-protein pregnant (LPP) rats were fed a low-protein diet (6%) from days 1 to 15 of pregnancy. The insulin secretion in 2.8 mmol l(-1) of glucose was higher in islets from LPP rats than that in islets from CP, CNP and LPNP rats. Maximal insulin release was obtained at 8.3 and 16.7 mmol l(-1) of glucose in LPP and CP groups, respectively. The glucose dose-response curve from LPNP group was shifted to the right in relation to the CNP group. In the CP group, the concentration-response curve to glucose was shifted to the left compared with the CNP group. The LPP groups exhibited an "inverted U-shape" dose-response curve. The alterations in the GLUT2, glucokinase and hexokinase expression patterns neither impaired glucose metabolism nor correlated with glucose islet sensitivity, suggesting that β-cell sensitivity to glucose requires secondary events other than the observed metabolic/molecular events.     

High dietary fish oil alters the brain polyunsaturated fatty acid composition

Feeding adult rats a 17% corn-oil diet for 8 weeks did not change brain polyunsaturated fatty acids (PUFA) compared to rats fed 2.2% corn oil (with 2.2% lard added). When the corn-oil diet was supplemented with 14.5% cod liver oil or 12.5% salmon oil, the fatty acid composition of brain PUFA was significantly altered, even if alpha-tocopherol was added to the salmon-oil diet. Comparing salmon-oil- and cod-liver-oil-fed animals with corn-oil-fed animals, arachidonic acid 22:4(n-6) and 22:5(n-6) were reduced, and 20:5(n-3), 22:5(n-3) and 22:6(n-3) were increased. Liver fatty acids were also significantly altered. Thus, the brain is not protected against a large excess of very-long-chain n-3 PUFA, which increase n-3/n-6 ratio and could lead to abnormal function, and which might be difficult to reverse.     

Human fetal and adult spleen phospholipids and their fatty acid composition

Total phospholipid contents and the individual phospholipid components of human adult and fetal spleens from 17--18 and 23--24 week's pregnancies composition of sphingomyelin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, diphosphatidylglycerol and phosphatidic acid studied in human adult, 17--18 and 23--24 week fetal spleens.     

Artificial rearing with docosahexaenoic acid and n-6 docosapentaenoic acid alters rat tissue fatty acid composition

Docosahexaenoic acid (DHA; 22:6n-3) and n-6 docosapentaenoic acid (DPAn-6; 22:5n-6) are components of enriched animal feed and oil derived from Schizochytrium species microalgae. A one generation, artificial rearing model from day 2 after birth onward (AR) and a dam-reared control group (DAM) were used to examine DPAn-6 feeding on the fatty acid composition of various rat tissues at 15 weeks of age. Four AR diets were based on an n-3 fatty acid-deficient, 18:2n-6-based artificial milk with 22:6n-3 and/or 22:5n-6 added: AR-LA, AR-DHA, AR-DPAn-6, and AR-DHA+DPAn-6. The 22:6n-3 levels for the DAM, AR-DHA, and AR-DHA+DPAn-6 groups tended to be similar and higher than in the AR-LA and AR-DPAn-6 groups. The levels of 22:5n-6 tended to be higher only in the absence of dietary 22:6n-3. Adipose levels of 22:5n-6 was the only exception, as 22:5n-6 was significantly higher in AR-DHA+DPAn-6 than was observed in either the DAM or the AR-DHA group. There were no differences in 20:4n-6 levels within the tissues examined. In conclusion, 22:5n-6 replaces 22:6n-3 in the absence of 22:6n-3 only and does not appear to compete with 22:6n-3 in the presence of dietary 22:6n-3, suggesting that oils containing 22:5n-6 and 22:6n-3 may be a good dietary source of 22:6n-3.     

Maternal training during lactation modifies breast milk fatty acid composition and male offspring glucose homeostasis in rat

The perinatal exposome can modify offspring metabolism and health later in life. Within this concept, maternal exercise during gestation has been reported modifying offspring glucose sensing and homeostasis, while the impact of such exercise during lactation is little-known. We thus aimed at evaluating short- and long-term effects of it on offspring pancreatic function, assuming a link with changes in breast milk composition. Fifteen-week-old primiparous female Wistar rats exercised during lactation at a constant submaximal intensity (TR) or remained sedentary (CT). Male offspring were studied at weaning and at 7 months of age for growth, pancreas weight, glycemia and insulin responses. Milk protein content was determined by the bicinchoninic acid assay (BCA colorimetric method), and lipid content and fatty acid composition by gas chromatography. Mature milk from TR rats contained significantly less saturated (?7 %) and more monounsaturated (+18 %) and polyunsaturated (PUFA +12 %) fatty acids compared to CT rats, with no difference in total lipid and protein concentrations. In offspring from TR vs CT mothers, fasting glycemia was lower, pancreas weight was higher with a lower insulin content (?37 %) at weaning. Such outcomes were correlated with milk PUFA levels and indices of desaturase or elongase activities. These effects were no longer present at 7 months, whereas a more efficient muscle insulin sensitivity was observed. Maternal training during lactation led to a specific milk phenotype that was associated with a short-term impact on glucose homeostasis and pancreatic function of the male offspring.     

Lipid and fatty acid composition of female gilthead seabream during their reproductive cycle: effects of a diet lacking n-3 HUFA

In female sea bream Sparus aurata fed a control diet (C), ovarian levels of neutral lipids (NL) and polar lipids (PL) remained constant between November and March, while a decrease in NL content was observed in liver and muscle. In the same period, liver PL content increased, while no changes were observed in muscle. Between March and June ovarian NL and PL showed a strong decrease, while NL remained constant in liver and muscle. When fish were fed a diet lacking in n-3 highly unsaturated fatty acids, n-3 HUFA (D), the pattern observed was similar to that found in the fish fed diet C, with the exception of liver NL, which increased between March and June. In general, the changes in fatty acid content, in both groups of fish, were highly influenced by the diet given to the broodstock, although these effects were greater on ovarian NL and PL than on liver and muscle lipids. Despite the fact that gilthead seabream females continue feeding during the spawning season, they probably make use of their liver and muscle reserves during the gonadal maturation process. Furthermore, the fatty acid composition of the broodstock diet was reflected in the body composition, especially in the ovaries.     

Medroxyprogesterone acetate therapy in early pregnancy has no apparent fetal effects

Medroxyprogesterone acetate (MPA; Provera) was given orally to 449 women from the 5th to 7th week of pregnancy until at least the 18th week. Data are recorded from two treatment groups (recurrent abortion and threatened abortion) and are compared to a matched series. A total of 1,016 pregnancies are included in the study, and all patients were recruited from a subfertile population conceiving from a range of infertility treatments. Early pregnancy wastage was high throughout the groups and was significantly elevated (43%; P less than .001) in those women who had vaginal bleeding in early pregnancy. The study focuses on the question of potential teratogenicity of progestagens administered in the first trimester. There were 15/366 (4.1%) infants with congenital abnormalities in the MPA-treated group and 15/428 in the untreated group (3.5%). The difference was not significant, and MPA is considered to have no embryopathic risk, nor is it likely to retain an abnormal fetus that might otherwise abort. It appears that MPA is a safe drug to use in pregnancy although the question of efficacy has not been addressed in this report. Considering other recent negative epidemiologic studies with regard to teratogenicity, we add to the conclusion that MPA cannot be demonstrated to have a measurable teratogenic risk and certainly does not present a risk for congenital heart disease and limb reduction defects.     

Maternal cadmium intoxication: effects on fetal brain antioxidant defense parameters

Summary

The antioxidant potential of the brain in developing fetuses was assessed at gestational days (GD) 16, 18 and 20 and postnatal day (PND)1. Higher activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) were noticed during fetal development which were reduced to about half and one-quarter, respectively, at PND 1. Glutathione reductase (GR) activity remained stationary throughout the experiment and the values were very high compared to those reported for weanling rats. In contrast, catalase (CAT) activity increased with development. Glutathione (GSH) and total sulfhydryls (TSH) were maximum in 16-day fetal brains and declined subsequently. Brain lipid peroxidation (LPO) was found to increase with age. A group of animals was exposed to 20 ppm cadmium (Cd) in drinking water from the day of conception up to PND 1. Cd was found to increase the activities of brain SOD, CAT, and GR significantly at all the time intervals. The metal exposure decreased fetal brain GPx at GD 18 and 20, whereas GPx activity declined precipitously in both groups on PND 1. Cd caused both increments and decrements in the GSH and TSH levels (depending on gestational day) and increased the LPO in brain. It may be concluded that the Cd-intoxicated fetal brain undergoes significant changes in antioxidant defense parameters which, overall, may be sufficient to permit near-normal development and prevent substantial oxidant damage.     

The effects of a diet rich in docosahexaenoic acid on organ and vascular fatty acid composition in spontaneously hypertensive rats

Previous research has shown that dietary docosahexaenoic acid (DHA) attenuates the development of high blood pressure in young spontaneously hypertensive rats (SHR). The purpose of this study was to investigate the effects of dietary DHA on organ and vascular fatty acid composition in SHR. Given the important structural and functional role of fatty acids in cell membranes, alterations in fatty acid composition may contribute to the antihypertensive effect of DHA. SHR were fed a purified diet containing either a corn/soybean oil mixture (CSO, control) or a DHA-enriched oil for 6 weeks. The DHA diet markedly increased the levels of DHA in the aorta, renal artery, plasma, liver, heart, kidney, and lung by 5-, 15-, 7-, 6-, 3.8-, 3.5-, and 8.8-fold (P<0.001), respectively. The levels of eicosapentaenoic acid were also increased while there was a concomitant reduction in arachidonic and adrenic acids. Therefore, dietary DHA increases the incorporation of omega-3 polyunsaturated fatty acids in specific organs and vascular tissue in SHR at the expense of omega-6 polyunsaturated fatty acids.     

Maternal age, gravidity, and pregnancy spacing effects on spontaneous fetal mortality

Differentials in the probability of pregnancy loss are examined using pregnancy history data from eight WFS surveys in developing countries. Multiple logistic regression equations are estimated. The probability of loss varies substantially over the reproductive career. Both higher-order pregnancies and those conceived at older ages are more likely to terminate in loss. maternal age differentials are more pronounced for lower-order pregnancies. First and second pregnancies conceived over age thirty suffer especially high levels of loss. Pregnancies conceived relatively soon after the termination of the previous pregnancy are more likely to be lost, as are pregnancies conceived after long intervals. Risk of loss is higher for women previously experiencing loss, and the effect persists beyond the pregnancy following the loss.     

Simultaneous estimation of diet composition and calibration coefficients with fatty acid signature data

Knowledge of animal diets provides essential insights into their life history and ecology, although diet estimation is challenging and remains an active area of research. Quantitative fatty acid signature analysis (QFASA) has become a popular method of estimating diet composition, especially for marine species. A primary assumption of QFASA is that constants called calibration coefficients, which account for the differential metabolism of individual fatty acids, are known. In practice, however, calibration coefficients are not known, but rather have been estimated in feeding trials with captive animals of a limited number of model species. The impossibility of verifying the accuracy of feeding trial derived calibration coefficients to estimate the diets of wild animals is a foundational problem with QFASA that has generated considerable criticism. We present a new model that allows simultaneous estimation of diet composition and calibration coefficients based only on fatty acid signature samples from wild predators and potential prey. Our model performed almost flawlessly in four tests with constructed examples, estimating both diet proportions and calibration coefficients with essentially no error. We also applied the model to data from Chukchi Sea polar bears, obtaining diet estimates that were more diverse than estimates conditioned on feeding trial calibration coefficients. Our model avoids bias in diet estimates caused by conditioning on inaccurate calibration coefficients, invalidates the primary criticism of QFASA, eliminates the need to conduct feeding trials solely for diet estimation, and consequently expands the utility of fatty acid data to investigate aspects of ecology linked to animal diets.