Decreased Docosahexaenoic Acid Levels Research Articles

Effects of a High-Fat Diet and Docosahexaenoic Acid during Pregnancy on Fatty Acid Composition in the Fetal Livers of Mice.

A high-fat diet (HFD) during pregnancy promotes fat accumulation and reduces docosahexaenoic acid (DHA) levels in the liver of the offspring at postnatal ages, which can depend on fetal sex. However, the prenatal mechanisms behind these associations are still unclear. Thus, we analyzed if an HFD alters DHA content and the expression of molecules related to fatty acid (FA) metabolism in the fetal liver. Female C57BL/6 mice were fed a control diet or HFD for 4-6 weeks before pregnancy until the gestational day (GD) 17.5. A subgroup of each diet received DHA (100 mg/Kg) orally from GD 6.5 until 16.5. On GD 17.5, maternal livers, placentas, and livers from male and female fetuses were collected for FA profiling with gas-chromatography and gene expression of molecules related to FA metabolism using qPCR. PPAR-α protein expression was evaluated using Western blot. The gene expression of placental FA transporters was also assessed. An HFD increased eicosapentaenoic acid (EPA) and decreased DHA levels and protein expression of PPAR-α in the fetal livers of both sexes. DHA increased the gene expression of Ppara, Cpt1, and Acsl1 in the livers of female fetuses. Therefore, an HFD reduces DHA levels and PPAR-α, a master regulator of gene expression, in the fetal liver. In turn, the livers of female fetuses seem to be more sensitive to DHA action.

Plasma arachidonic and docosahexaenoic acids in Tunisian very low birth weight infants: status and association with selected neonatal morbidities.

To study plasma arachidonic acid (AA) and docosahexaenoic acid (DHA) status in Tunisian very low birth weight (VLBW) infants and their association with selected neonatal morbidities. A total of 709 VLBW infants and 339 term infants were included. Plasma fatty acids were analyzed using capillary gas chromatography. VLBW infants had significantly (p < 0.001) lower plasma AA (9.44 ± 2.12 vs. 10.8 ± 2.10) and DHA (2.56 ± 0.89 vs. 3.46 ± 1.09) levels, but higher n-6:n-3 ratio (5.58 ± 1.22 vs. 5.17 ± 1.46) than term infants. In VLBW infants, plasma AA and DHA were related to gestational age (r = 0.156; p = 0.001 and r = 0.134; p = 0.003, respectively), birthweight (r = 0.242; p < 0.001 and r = 0.181; p < 0.001, respectively) and head circumference (r = 0.138; p = 0.005 and r = 0.108; p = 0.027, respectively). Infants with respiratory distress syndrome have decreased plasma AA and DHA and those with intraventricular hemorrhage have decreased plasma AA and n-6:n-3 ratio. Sepsis was associated with decreased DHA levels. Plasma long chain polyunsaturated fatty acids status is low in VLBW infants. These deficits may enhance the risk of common neonatal morbidities, rendering their prevention and correction greatly warranted.

Linoleic and α-linolenic acid as precursor and inhibitor for the synthesis of long-chain polyunsaturated fatty acids in liver and brain of growing pigs

Studies suggested that in human adults, linoleic acid (LA) inhibits the biosynthesis of n-3 long-chain polyunsaturated fatty acids (LC-PUFA), but their effects in growing subjects are largely unknown. We used growing pigs as a model to investigate whether high LA intake affects the conversion of n-3 LC-PUFA by determining fatty acid composition and mRNA levels of Δ5- and Δ6 desaturase and elongase 2 and -5 in liver and brain. In a 2 × 2 factorial arrangement, 32 gilts from eight litters were assigned to one of the four dietary treatments, varying in LA and α-linolenic acid (ALA) intakes. Low ALA and LA intakes were 0.15 and 1.31, and high ALA and LA intakes were 1.48 and 2.65 g/kg BW0.75 per day, respectively. LA intake increased arachidonic acid (ARA) in liver. ALA intake increased eicosapentaenoic acid (EPA) concentrations, but decreased docosahexaenoic acid (DHA) (all P < 0.01) in liver. Competition between the n-3 and n-6 LC-PUFA biosynthetic pathways was evidenced by reductions of ARA (>40%) at high ALA intakes. Concentration of EPA (>35%) and DHA (>20%) was decreased by high LA intake (all P < 0.001). Liver mRNA levels of Δ5- and Δ6 desaturase were increased by LA, and that of elongase 2 by both ALA and LA intakes. In contrast, brain DHA was virtually unaffected by dietary LA and ALA. Generally, dietary LA inhibited the biosynthesis of n-3 LC-PUFA in liver. ALA strongly affects the conversion of both hepatic n-3 and n-6 LC-PUFA. DHA levels in brain were irresponsive to these diets. Apart from Δ6 desaturase, elongase 2 may be a rate-limiting enzyme in the formation of DHA.

Fish oil supplementation of maternal rats on an n-3 fatty acid-deficient diet prevents depletion of maternal brain regional docosahexaenoic acid levels and has a postpartum anxiolytic effect

Docosahexaenoic acid (DHA) and arachidonic acid (AA) are the major polyunsaturated fatty acids (PUFA) in the neuronal membrane. Most DHA and AA accumulation in the brain occurs during the perinatal period via placenta and milk. This study examined whether maternal brain levels of DHA and AA are depleted during pregnancy and lactation due to meeting the high demand of the developing nervous system in the offspring and evaluated the effects of the reproductive cycle on serotonin metabolism and of fish oil (FO) on postpartum anxiety. Pregnant rats were fed during pregnancy and lactation with a sunflower oil-based n-3 PUFA-deficient diet without or with FO supplementation, which provided 0.37% of the energy source as n-3 PUFA, and the age-matched virgin rats were fed the same diets for 41 days. In both sets of postpartum rats, decreased DHA levels compared to those in virgin females were seen in the hypothalamus, hippocampus, frontal cortex, cerebellum, olfactory bulb and retina, while AA depletion was seen only in the hypothalamus, hippocampus and frontal cortex. Serotonin levels were decreased and turnover increased in the brainstem and frontal cortex in postpartum rats compared to virgin rats. FO supplementation during pregnancy and lactation prevented the decrease in maternal brain regional DHA levels, inhibited monoamine oxidase-A activity in the brainstem and decreased anxiety-like behavior. We propose that the reproductive cycle depletes maternal brain DHA levels and modulates maternal brain serotonin metabolism to cause postpartum anxiety and suggest that FO supplementation may be beneficial for postpartum anxiety in women on an n-3 PUFA-deficient diet.

Response to Comment on: Tikhonenko et al. (2010) Remodeling of Retinal Fatty Acids in an Animal Model of Diabetes: A Decrease in Long-Chain Polyunsaturated Fatty Acids Is Associated with a Decrease in Fatty Acid Elongases Elovl2 and Elovl4. Diabetes;59:219–227

We thank Byeon and Chu (1) for initiating the discussion about potential mechanisms of decreased docosahexaenoic acid (DHA) levels in diabetic eyes. The authors refer to their recent case report from two diabetic patients showing lower ratios of DHA in retinal hard exudates relative to plasma phospholipid levels. They speculate that lower levels of DHA in hard exudates are the result of higher DHA degradation; however, no direct evidence for DHA oxidation is provided in the study. Although we cannot speak to the mechanism of low DHA levels in hard exudates, we would …

Docosahexaenoic acid attenuates microglial activation and delays early retinal degeneration

Microgliosis is a common phenomenon in neurodegenerative disorders including retinal dystrophies. We performed a detailed characterization of activated microglia in the retinoschisin (Rs1h)-deficient (Rs1h(-/Y)) mouse model of inherited retinal degeneration. To visualize and isolate microglia, we crossed Rs1h(-/Y) animals with transgenic MacGreen mice, which express green fluorescent protein under the control of the macrophage-specific csf1r promoter. Activated microglia were detected in retinal sections and whole-mounts of early postnatal MacGreen/Rs1h(-/Y) mice before the onset of overt neuronal cell death. These activated microglia contained prominent lipid droplets and analysis of the retinal lipid composition showed decreased docosahexaenoic acid (DHA) levels in Rs1h(-/Y) retinas. To establish a link between microglia activation, reduced DHA levels, and neurodegeneration, a dietary intervention study was performed. Female Rs1h(-/-) mice and their Rs1h(-/Y) litter were either subjected to a diet enriched with DHA, or a control chow lacking DHA. Supplementation with DHA enhanced photoreceptor survival and converted activated microglia to a quiescent phenotype. Furthermore, DHA, but not docosapentaenoic acid or adrenic acid reduced pro-inflammatory gene expression, migration, and lipid accumulation of cultured BV-2 microglia. We conclude that retinal DHA levels control the activity of microglia and thereby may affect the progression and extent of retinal degeneration.

Brain Docosahexaenoic Acid Status and Learning in Young Rats Submitted to Dietary Long-Chain Polyunsaturated Fatty Acid Deficiency and Supplementation Limited to Lactation

N-3 fatty acid deficiency has been related to decreased docosahexaenoic acid (DHA) and increased docosapentaenoic acid (DPA) levels in brain and to learning disadvantages. The influence of n-3 deficiency and supplementation on brain fatty acids and learning were investigated in young rats. Newborn Wistar rats were assigned to three groups of cross-foster mothers. The control group (C) was nursed by mothers that received essential fatty acids during pregnancy and lactation, and the deficient group (D) was nursed by mothers that did not receive those fatty acids. The supplemental group (S) had the same conditions as D, receiving an additional DHA and arachidonic acid supplement during lactation. Cerebral cortex and hippocampus fatty acid composition was examined using thin-layer and capillary column gas chromatography, and learning was measured by passive-avoidance procedure. D brains showed low DHA and high DPA levels, but S brain composition was similar to C. Learning in the S group was unaffected, but in the D group, it was poorer than C. Learning was directly correlated with DHA levels and inversely with DPA levels in brain. Low DHA and high DPA brain levels both were correlated with poor learning. DPA seems not to be a suitable brain functional analogue of DHA, and DHA supplementation reversed both biochemical and learning adverse effects observed in n-3 deficiency.

Water Maze Performance Is Unaffected in Artificially Reared Rats Fed Diets Supplemented with Arachidonic Acid and Docosahexaenoic Acid

Four groups of male Long-Evans rats were reared artificially from postnatal d 5 to 18 by being fed through a gastrostomy tube with rat milk substitutes containing oils providing 10% linoleic acid and 1% α-linolenic acid (g/100 g fat); with the use of a 2 × 2 design, they were fed one of two levels of arachidonic acid (AA) and docosahexaenoic acid (DHA) (0.0 and 2.5 g/100 g of fatty acids). A fifth artificially reared group was fed a diet high in saturated fat, and a sixth group was reared by dams fed a standard AIN-93M diet. The pups were weaned onto modified AIN-93G diets, with a fat composition similar to that fed during the artificial rearing period. Behavioral testing was conducted between 6 and 9 wk of age; brain lipid composition was then assessed. Relative to the unsupplemented group (0.0 g/100 g AA and DHA), dietary supplementation resulted in a wide range of AA (84–103%) and particularly DHA (86–119%) levels in forebrain membrane phospholipids. AA supplementation increased AA levels and decreased DHA levels, and DHA supplementation increased DHA levels and decreased AA levels, with the magnitude of these effects dependent on the level of the other fatty acid. DHA levels were very low in the saturated fat group. The groups did not differ on the place or cued version of the Morris water-maze, but on a test of working memory, the saturated fat group was impaired relative to the suckled control group. Further correlational analyses in the artificially reared animals did not support a relationship between the wide range of DHA and AA levels in the forebrain and working-memory performance.

Thermogenesis and fatty acid composition of brown adipose tissue in rats rendered hyperthyroid and hypothyroid-with special reference to docosahexaenoic acid.

The effects of hyperthyroidism and hypothyroidism on brown adipose tissue (BAT) thermogenesis and phospholipid fatty acid composition were investigated in rats. Chronic triiodothyronine (T3) treatment (hyperthyroidism) increased the interscapular BAT pad weight, its triacylglycerol content, and its DNA content. It did not affect basal and noradrenaline-stimulated in vitro oxygen consumption of BAT expressed per microg DNA, although it significantly increased the oxygen consumption of the whole BAT pad. T3 treatment had little effect on phospholipid content and phospholipid fatty acid composition. In contrast, chronic methimazole treatment (hypothyroidism) decreased the BAT pad weight and the triacylglycerol content, but did not significantly change the DNA content in comparison with the control. It significantly decreased the noradrenaline-stimulated BAT oxygen consumption expressed per microg DNA and per BAT pad, but did not change the basal oxygen consumption. Methimazole treatment significantly affected phospholipid content and phospholipid fatty acid composition. Among the major fatty acids of BAT, it decreased docosahexaenoic acid (DHA), arachidonic acid, palmitic acid, palmitoleic acid, and oleic acid, and it increased linoleic acid, stearic acid, and eicosapentaenoic acid. A regression analysis revealed a positive relationship between in vitro respiration and DHA levels in phospholipids (r = 0.404, p<0.05). These results suggest that thyroid hormones have trophic action on BAT and are necessary for BAT thermogenic activity. This study also suggests that DHA is involved in the regulation of BAT thermogenic activity, as we previously indicated.