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Chemical Compound Review

Docosahexaenoic acids     (4E,7E,10Z,13E,16E,19E)- docosa-4,7,10,13...

Synonyms: LS-182914, AKOS015914068, AC1O5GX8
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Disease relevance of Docosahexaenoic acid


Psychiatry related information on Docosahexaenoic acid

  • Decreased docosahexaenoic acid (DHA) and brain-derived neurotrophic factor (BDNF) have been implicated in bipolar disorder [6].
  • Research is needed (1) to probe the effects of variable DHA exposure on infant and child development, (2) to measure outcomes that better relate to preschool and school-age cognitive function, and (3) to reinforce, and in some cases demonstrate, links between specific infant and preschool measures of cognitive development [7].
  • Our own unpublished observations from the Framingham Heart Study suggest that > or =180 mg/d of dietary DHA (approximately 2.7 fish servings/wk) is associated with an approximately 50% reduction in dementia risk [8].
  • CONCLUSIONS: The results of this study suggest that for full-term infants, breast-feeding is associated with enhanced stereopsis at age 3.5 y, as is a maternal DHA-rich antenatal diet, irrespective of later infant feeding practice [9].
  • The amount of DHA in human milk varies widely and is positively correlated with visual and language development in breast-fed infants [10].

High impact information on Docosahexaenoic acid


Chemical compound and disease context of Docosahexaenoic acid


Biological context of Docosahexaenoic acid

  • Biophysical experiments have shown that lipid unsaturation and cholesterol both have significant effects on rhodopsin's stability and function; omega-3 polyunsaturated chains, such as docosahexaenoic acid (DHA), destabilize rhodopsin and enhance the kinetics of the photocycle, whereas cholesterol has the opposite effect [20].
  • To determine the effects of n-3 fatty acids on aged rat brain, 2-year-old rats were fed fish oil (27% DHA content) for 1 month, and gene expression analysis and fatty acid and molecular species composition of the major phospholipid species were assessed [21].
  • This lipid imbalance was observed in organs pathologically affected by CF including lung, pancreas, and ileum and was not secondary to impaired intestinal absorption or hepatic biosynthesis of DHA [22].
  • DHA treatment resulted in marked inhibition of TPA- and EGF-induced cell transformation by inhibiting AP-1 transactivation [3].
  • DHA is involved in memory formation, excitable membrane function, photoreceptor cell biogenesis and function, and neuronal signaling, and has been implicated in neuroprotection [23].

Anatomical context of Docosahexaenoic acid

  • An n-3 polyunsaturated fatty acid (docosahexaenoic acid (DHA)) suppressed NFkappaB activation and cyclooxygenase-2 expression induced by the agonist for TLR2, 3, 4, 5, or 9 in a macrophage cell line (RAW264.7) [24].
  • Pharmacoepidemiological data, analytical data from human tissue and body fluids, and mechanistic data mostly from murine models all have implicated oxidation products of two fatty acids, arachidonic acid (AA) and docosahexaenoic acid (DHA), in the pathogenesis of neurodegeneration [25].
  • The addition of DHA to rat primary cortical astrocytes in vitro, induced BDNF protein expression and this was blocked by a p38 MAPK inhibitor [6].
  • EPA/DHA increased plasma adiponectin levels, independent of food intake, reflecting the stimulation of Adipoq expression in adipocytes and the release of adiponectin from WAT, particularly from epididymal fat [26].
  • Plasma phospholipid AA and DHA increased approximately 18% and 50%, respectively, with the 1 x dose, similar to that expected at intakes provided by human milk [27].

Associations of Docosahexaenoic acid with other chemical compounds

  • By analyzing the results of 26 independent 100-ns simulations of dark-adapted rhodopsin, we found that DHA routinely forms tight associations with the protein in a small number of specific locations qualitatively different from the nonspecific interactions made by saturated chains and cholesterol [20].
  • EPA and DHA were subjected to an in vitro free radical oxidation process that models in vivo conditions [28].
  • Consumption of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can mitigate the progression of diseases in which oxidative stress represents a common underlying biochemical process [28].
  • RESULTS: In mice with free access to food, plasma triacylglycerols, NEFA, and insulin levels were lower in the presence of EPA/DHA, while glucose and leptin levels were not significantly altered [26].
  • METHODS: The effects of pregnancy and lactation on brain phospholipid fatty acid content were determined in female rats fed diets containing sufficient (control) or negligible (deficient) alpha-linolenic acid (18:3n-3), the dietary precursor of DHA, beginning at conception [29].

Gene context of Docosahexaenoic acid

  • Additionally, DHA and EPA significantly suppressed COX-2 expression induced by a synthetic lipopeptide, a TLR2 agonist [30].
  • These results indicate that EPA and DHA act in opposition to AA by modulating various steps of the inflammatory process induced by IL1 beta, probably by reducing mitogen-activated protein kinase p42/p44 activity [31].
  • The target of inhibition by DHA is TLR itself or its associated molecules, but not downstream signaling components [30].
  • Palmitate, but not DHA or laurate, induced nuclear factor kappaB (NF-kappaB)-driven luciferase activity and interleukin-6 (IL-6) expression (P < 0.05) [32].
  • Finally, we have shown that the incorporation of EPA and DHA also increased the concentration of caveolin-1 and caveolin-3 in caveolae, which correlated with n-3 PUFA inhibition of SMC proliferation through the mitogen-activated protein kinase pathway [33].

Analytical, diagnostic and therapeutic context of Docosahexaenoic acid

  • As proof of concept, oral administration of DHA to cftr(-/-) mice corrected this lipid imbalance and reversed the observed pathological manifestations [22].
  • Expression of Lep and the release of leptin from WAT, while being extremely sensitive to caloric restriction, was unaltered by EPA/DHA [26].
  • By ages 17 and 39 wk, the red blood cell DHA concentration in the LCP-supplemented group was more than double and more than triple, respectively, that in the control group [34].
  • Erythrocyte DHA concentrations were 30-40% higher after the n-3 egg intervention than after treatment with regular eggs or no eggs in both breast-fed and formula-fed infants [35].
  • Pregravid body mass index was negatively associated with plasma phospholipid DHA (% by wt) in control subjects (r = -0.55, P = 0.04) and in women with GDM with a body mass index (in kg/m2) <30 (r = -0.76, P = 0.007) [36].


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