Phospholipid Docosahexaenoic Acid Content Research Articles

Protective Effects of Eicosapentaenoic Acid Plus Hydroxytyrosol Supplementation Against White Adipose Tissue Abnormalities in Mice Fed a High-Fat Diet.

Objective: Obesity induced by high-fat diet (HFD) elicits white adipose tissue dysfunction. In this study, we have hypothesized that the metabolic modulator eicosapentaenoic acid (EPA) combined with the antioxidant hydroxytyrosol (HT) attenuates HFD-induced white adipose tissue (WAT) alterations. Methods: C57BL/6J mice were administered with a HFD (60% fat, 20% protein, 20% carbohydrates) or control diet (CD; 10% fat, 20% protein, 70% carbohydrates), with or without EPA (50 mg/kg/day), HT (5 mg/kg/day), or both for 12 weeks. Determinations in WAT include morphological parameters, EPA and docosahexaenoic acid content in phospholipids (gas chromatography), lipogenesis, oxidative stress (OS) and inflammation markers, and gene expression and activities of transcription factors, such as sterol regulatory element-binding protein-1c (SREBP-1c), peroxisome proliferator-activated receptor-gamma (PPAR-γ), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) (p65 subunit) and nuclear factor erythroid 2-related factor 2 (Nrf2) (quantitative polymerase chain reaction and enzyme linked immunosorbent assay). Results: HFD led to WAT hypertrophy in relation to PPAR-γ downregulation. WAT metabolic dysfunction was characterized by upregulation of lipogenic SREBP-1c system, mitochondrial energy metabolism depression, loss of the antioxidant Nrf2 signaling with OS enhancement, n-3 long-chain polyunsaturated fatty acids depletion and activation of the pro-inflammatory NF-κB system. EPA and HT co-supplementation diminished HFD-dependent effects additively, reaching values close or similar to controls. Conclusion: Data presented strengthen the importance of combined protocols such as EPA plus HT to attenuate metabolic-inflammatory states triggered by obesity.

The metabolic dysfunction of white adipose tissue induced in mice by a high-fat diet is abrogated by co-administration of docosahexaenoic acid and hydroxytyrosol.

Nutritional interventions are promising tools for the prevention of obesity. The n-3 long-chain polyunsaturated fatty acid (n-3 LCPUFA) docosahexaenoic acid (DHA) modulates immune and metabolic responses while the antioxidant hydroxytyrosol (HT) prevents oxidative stress (OS) in white adipose tissue (WAT). The DHA plus HT combined protocol prevents WAT alterations induced by a high-fat diet in mice. Main related mechanisms. Male C57BL/6J mice were fed a control diet (CD; 10% fat, 20% protein, and 70% carbohydrates) or a high fat diet (HFD) (60% fat, 20% protein, and 20% carbohydrates) for 12 weeks, without and with supplementation of DHA (50 mg kg-1 day-1), HT (5 mg kg-1 day-1) or both. Measurements of WAT metabolism include morphological parameters, DHA content in phospholipids (gas chromatography), lipogenesis, OS and inflammation markers, mitochondrial activity and gene expression of transcription factors SREBP-1c, PPAR-γ, NF-κB (p65) and Nrf2 (quantitative polymerase chain reaction and enzyme-linked immunosorbent assay). The combined DHA and HT intervention attenuated obesity development, suppressing the HFD-induced inflammatory and lipogenic signals, increasing antioxidant defenses, and maintaining the phospholipid LCPUFA n-3 content and mitochondrial function in WAT. At the systemic level, the combined intervention also improved the regulation of glucose and adipokine homeostasis. The combined DHA and HT protocol appears to be an important nutritional strategy for the treatment of metabolic diseases, with abrogation of obesity-driven metabolic inflammation and recovery of a small-healthy adipocyte phenotype.

The influence of orally administered docosahexaenoic acid on monoamine neurotransmitter, nerve growth factor, and brain-derived neurotrophic factor in aged mice

In this study we attempt to investigate the new role of docosahexaenoic acid (DHA) supplementation on cognitive ability in aged mice. Kunming-line mice were treated with DHA (200, 400 mg/kg body weight/day) for 30 successive days. The cognitive ability of mice was assessed by learning and memory behavioral test; the levels of DHA were assessed by capillary gas chromatography; the levels of dopamine (DA), norepinephrine (NE), and 5-hydroxytryptamine (5-HT) were assessed by high-performance liquid chromatography; the levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) proteins were assessed by the enzyme-linked immunosorbent assay method. The results showed the cognitive ability of mice were significantly different between the DHA-treated groups and the aged group, and orally administered DHA can increase the levels of DA, NE and 5-HT, the content of BDNF and NGF proteins in hippocampus, frontal cortex and striatum tissues. In addition, aged-related changes in phospholipid DHA content were seen. Decreases in DHA were mostly corrected by DHA supplementation. These novel data suggest that DHA supplementation can improve the cognitive dysfunction due to aging by increasing the levels of BDNF and NGF protein and the levels of DA, NE, 5-HT to some extent. We speculate that the mechanism of DHA on cognitive ability may have a beneficial effect on signaling networks through modulation of monoamine neurotransmitters and neurotrophic factors in brain aging.

Docosahexaenoic Acid (DHA) Supplementation of Orange Juice Increases Plasma Phospholipid DHA Content of Children

The major dietary source of docosahexaenoic acid (DHA) is fish, which is not widely consumed by children. There is concern, therefore, that children may not receive adequate DHA and so might benefit from dietary supplementation. The aim of the present study was to evaluate the effects of providing a supplement of microencapsulated algal DHA in juice. We assessed the effects of two levels of DHA supplementation on the plasma phospholipid DHA content of healthy 4- to 6-year-old and 7- to 12-year-old children who were randomly assigned to consume 180 mL juice containing either 50 mg (lower dose) or 100 mg (higher dose) DHA daily for 6 weeks. Plasma phospholipid DHA content (mole % of total fatty acids) was measured before and after 6 weeks of daily juice consumption. Because there are no data for plasma phospholipid DHA content in healthy children, data were compared to that of breastfed infants. At baseline, plasma phospholipid DHA content was lower in both age groups and dose groups than observed in breastfed infants. It increased significantly in both dose groups, but more so in the higher dose group of both age groups ( P<0.05, overall mean±standard deviation: 3.72±0.66 vs 4.64±0.77); reaching levels similar to or greater than content of breastfed infants. Thus, DHA supplementation of juice at either 50 mg/day or 100 mg/day for 6 weeks was effective in increasing plasma phospholipid DHA contents of children.

Docosahexaenoic acid increases doxorubicin's cytotoxicity against breast cancer cell lines

It is well established that long chain n‐3 polyunsaturated fatty acids have cytotoxic effects on human breast cancer cells. To determine synergy between n‐3 fatty acids and chemotherapy drugs, we examined the effects of docosahexaenoic acid (DHA) alone and in combination with doxorubicin (DOX) on growth of MDA‐MB‐231 and MCF‐7 human breast cancer cell lines, using the WST‐1 assay. The dose/concentration associated with 50% inhibition (IC50) was determined for DHA and DOX (individually) on both cell lines. After treatment (48h) with DHA at its IC50 concentration (320 μM for MCF‐7, 87 μM for MDA‐MB‐231), cells were treated with DOX at its IC50 (5.1 μM for MCF‐7, 0.3 μM for MDA‐MB‐231); resulting in increased inhibition (compared to individual treatments). Incubation with DHA significantly increased DHA content in phospholipids of both cell lines. Isobologram analysis (using the Calcusyn program) indicated a synergistic relationship for DHA in MCF‐7 cells, and an additive relationship for DHA in MDA‐MB‐231 cells. Our results suggest that incorporation of DHA into two different breast cancer cell lines can improve the cytotoxic effects DOX which is a cornerstone of breast cancer chemotherapy. Canadian Breast Cancer Foundation: Prairies/NWT

A randomized, double-blind, placebo-controlled trial of docosahexaenoic acid supplementation in children with attention-deficit/hyperactivity disorder

Objective: To determine whether docosahexaenoic acid (DHA) supplementation for 4 months decreases the symptoms of attention-deficit/hyperactivity disorder (ADHD). Study design: Sixty-three 6- to-12-year-old children with ADHD, all receiving effective maintenance therapy with stimulant medication, were assigned randomly, in a double-blind fashion, to receive DHA supplementation (345 mg/d) or placebo for 4 months. Outcome variables included plasma phospholipid fatty acid patterns, scores on laboratory measures of inattention and impulsivity (Test of Variables of Attention, Children’s Color Trails test) while not taking stimulant medication, and scores on parental behavioral rating scales (Child Behavior Checklist, Conners’ Rating Scale). Differences between groups after 4 months of DHA supplementation or placebo administration were determined by analysis of variance, controlling for age, baseline value of each outcome variable, ethnicity, and ADHD subtype. Results: Plasma phospholipid DHA content of the DHA-supplemented group was 2.6-fold higher at the end of the study than that of the placebo group (4.85 ± 1.35 vs 1.86 ± 0.87 mol % of total fatty acids; P <.001). Despite this, there was no statistically significant improvement in any objective or subjective measure of ADHD symptoms. Conclusion: A 4-month period of DHA supplementation (345 mg/d) does not decrease symptoms of ADHD. (J Pediatr 2001;139:189-96)

Effect of dietary linoleic/alpha-linolenic acid ratio on growth and visual function of term infants

Objectives: To determine the effect of α-linolenic acid (ALA) intake (or the dietary linoleic acid [LA]/ALA ratio) on the growth and visual function of term infants. Study design: Normal term infants were assigned randomly and in masked fashion at birth to receive formulas with approximately 16% of total fatty acids as LA and 0.4%, 1.0%, 1.7%, or 3.2% of fatty acids as ALA (LA/ALA ratios of 44, 18.2, 9.7, and 4.8) for the first 4 months of life. The fatty acid pattern of plasma phospholipids was determined shortly after birth and at approximately 21, 60, and 120 days of age. Anthropometric data were obtained at the same times and also at approximately 240 days of age. Transient visual evoked responses (VERs) were measured at approximately 120 and 240 days of age. For comparisons, anthropometric and VER data also were obtained in infants who were exclusively breast-fed for the first 4 months of life. Results: Infants who received the formula with 3.2% ALA (LA/ALA ratio, 4.8) had higher plasma concentrations of phospholipid docosahexaenoic acid (DHA) but lower concentrations of arachidonic acid at 21, 60, and 120 days of age. Mean weight of this group at 120 days of age was 760 gm less ( p < 0.05) than the mean weight of the group that received the formula with 0.4% ALA (LA/ALA ratio, 44). Despite differences in plasma phospholipid DHA contents among groups, neither VER latency nor amplitude differed significantly among formula groups or between any formula group and age-matched, breast-fed infants. Conclusions: The highest versus the lowest ALA intake (or the lowest vs the highest LA/ALA ratio) resulted in higher plasma phospholipid DHA content from 21 to 120 days of age but was not associated with improved visual function as assessed by transient VER. Moreover, mean body weight of infants who received the highest versus lowest ALA intake was less at 120 days ( p < 0.05). These data suggest that the lower LA/ALA ratios currently recommended for infant formulas should not be adopted until the effect of such ratios on growth are evaluated more completely. (J Pediatr 1997;131:200-9)

Membrane docosahexaenoic acid vs. eicosapentaenoic acid and the beating function of the cardiomyocyte and its regulation through the adrenergic receptors

The beta-adrenergic system in cardiac muscle cells is influenced by the n-3 polyunsaturated fatty acid (PUFA) content in cell membranes. This study deals with the specific effect of docosahexaenoic acid (DHA) as compared to other n-3 PUFA, without modification of the arachidonic acid content. Increasing the DHA content in the phospholipids of isolated cardiomyocytes did not provoke electrical or contraction modifications, except for a slightly lower plateau phase (-2 mV). Conversely, the beta-adrenergic function was affected at several levels: (i) the receptor affinity for dihydroalprenolol tended to decrease (Kd) without alteration of the number of beta-binding sites (beta max); (ii) the isoproterenol-induced (10(-7) M and 10(-6) M) cAMP production was significantly decreased (-20%); and (iii) the positive chronotropic response to beta-adrenergic stimulation (isoproterenol, 10(-7) M) was significantly enhanced (+80%). In order to further investigate the relationship between the decreased cAMP and the increased chronotropic response, the cells were treated with dibutyryl-cAMP, a permeant analogue of cAMP, which elicited a significantly higher chronotropic response in DHA-enriched cells than in EPA-enriched cells +50%). The increase in DHA content in cardiac cell membranes phospholipids may thus affect the beta-adrenergic system through an increase of cAMP efficiency. Although the membrane phosphatidylinositols were largely involved in the PUFA alterations, none of the parameters related to alpha-adrenergic system (chronotropic response, receptor density, affinity for prasozin, and inositide phosphate production) were influenced by the membrane DHA content.

Infusion of fish oil emulsion: effects on platelet aggregation and fatty acid composition in phospholipids of plasma, platelets, and red blood cell membranes in rabbits

An emulsion of fish oil was manufactured to contain 10 g of fish oil/100 mL. Of this, 3 g were eicosapentaenoic acid (EPA) and 1 g was docosahexaenoic acid (DHA). We administered 100 mL of the emulsion into six rabbits intravenously on days 1, 4, 7, 10, and 13. Blood samples were taken on days 0 and 16. The EPA content in phospholipids of plasma, platelets, and red blood cell (RBC) membranes increased 16, 4, and 5 times, respectively. The DHA content in phospholipids of plasma and RBC membranes increased two times whereas that in platelet phospholipids did not increase significantly. Platelet aggregation induced by collagen (10 micrograms/mL) and ADP (5 microM) was depressed significantly after infusion of the fish oil emulsion. In control experiments with soybean oil emulsion, there were almost no significant changes. Therefore, fish oil emulsion may be beneficial to patients who cannot take n-3 fatty acids orally but need them.