Rapid β-oxidation of eicosapentaenoic acid in mouse brain: An in situ study

Chen, Chuck T.; Liu, Zhen; Ouellet, Mélissa; Calon, Frédéric; Bazinet, Richard P.

doi:10.1016/j.plefa.2009.01.005

Cited by 134 publications

(97 citation statements)

References 76 publications

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“…Although this study focused on n-3 PUFA kinetics and concentrations, future studies should test the effects of aging on n-6 PUFA liver kinetics. Rates of incorporation of unesterified circulating DHA and AA into brain reflect their respective rates of loss from brain due to metabolism, as the shorter chain PUFAs that enter brain largely undergo rapid oxidation (Demar et al 2005;DeMar et al 2006;Chen et al 2009;Chen et al 2011). As biomarkers of brain PUFA integrity, unesterified plasma DHA and AA concentrations may be more informative than the respective esterified concentrations (Kuriki et al 2003;Rapoport et al 2011).…”

Section: Ementioning

confidence: 99%

RETRACTED ARTICLE: Aging decreases rate of docosahexaenoic acid synthesis-secretion from circulating unesterified α-linolenic acid by rat liver

Gao

Taha

et al. 2012

AGE

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Docosahexaenoic acid (DHA,, an n-3 polyunsaturated fatty acid (PUFA) found at high concentrations in brain and retina and critical to their function, can be obtained from fish products or be synthesized from circulating α-linolenic acid (α-LNA, 18:3n-3) mainly in the liver. With aging, liver synthetic enzymes are reported reduced or unchanged in the rat. To test whether liver synthesis-secretion of DHA from α-LNA changes with age, we measured whole-body DHA conversion coefficients and rates in unanesthetized adult male Fischer-344 rats aged 10, 20, or 30 months, fed an eicosapentaenoic acid (EPA, 20:5n-3)-and DHAcontaining diet. Unesterified [U-13 C]α-LNA bound to albumin was infused intravenously for 2 h, while [ 13 C]-esterified n-3 PUFAs were measured in arterial plasma, as were unlabeled unesterified and esterified PUFA concentrations. Plasma unesterified n-3 PUFA concentrations declined with age, but esterified n-3 PUFA concentrations did not change significantly. Calculated conversion coefficients were not changed significantly with age, whereas synthesis-secretion rates (product of conversion coefficient and unesterified plasma α-LNA concentration) of esterified DHA and n-3 DPA were reduced. Turnovers of esterified n-3 PUFAs in plasma decreased with age, whereas half-lives increased. The results suggest that hepatic capacity to synthesize DHA and other n-3 PUFAs from circulating α-LNA is maintained with age in the rat, but that reduced plasma α-LNA availability reduces net synthesis-secretion. As unesterified plasma DHA is the form that is incorporated preferentially into brain phospholipid, its reduced synthesis may be deleterious to brain function in aged rats.

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Section: Ementioning

confidence: 99%

RETRACTED ARTICLE: Aging decreases rate of docosahexaenoic acid synthesis-secretion from circulating unesterified α-linolenic acid by rat liver

Gao

Taha

et al. 2012

AGE

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“…DHA is quantitatively the most important omega-3 PUFA in the brain, and brain DHA levels are typically 250-300 times higher than EPA (Chen et al, 2009). The low levels of EPA are maintained by multiple mechanisms including -oxidation, decreased incorporation, elongation to docosapentaenic acid (DPA, 22:5n-3) and lower phospholipid recycling (Chen et al, 2013).…”

mentioning

confidence: 99%

Distinctive effects of eicosapentaenoic and docosahexaenoic acids in regulating neural stem cell fate are mediated via endocannabinoid signalling pathways

et al. 2016

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Running title: EPA, but not DHA induces proliferation in NSCs Abbreviations: AA, Arachidonic acid, AEA, anandamide, DHA. Docosahexaenoic acid; EPA, eicosapentaenoic acid, 2-AG, 2-arachidonylglycerol 2 Title: Distinctive effects of eicosapentaenoic and docosahexaenoic acids in regulating neural stem cell fate are mediated via endocannabinoid signalling pathways Emerging evidence suggests a complex interplay between the endocannabinoid system, omega-3 fatty acids and the immune system in the promotion of brain self-repair. However, it is unknown if all omega-3 fatty acids elicit similar effects on adult neurogenesis and if such effects are mediated or regulated by interactions with the endocannabinoid system. This study investigated the effects of DHA and EPA on neural stem cell (NSC) fate and the role of the endocannabinoid signalling pathways in these effects.EPA, but not DHA, significantly increased proliferation of NSCs compared to controls, an effect associated with enhanced levels of the endocannabinoid 2-arachidonylglycerol (2-AG) and p-p38 MAPK, effects attenuated by pre-treatment with CB1 (AM251) or CB2 (AM630) receptor antagonists. Furthermore, in NSCs derived from IL-1 deficient mice, EPA significantly decreased proliferation and p-p38 MAPK levels compared to controls, suggesting a key role for IL-1 signalling in the effects observed. Although DHA similarly increased 2-AG levels in wild-type NSCs, there was no concomitant increase in proliferation or p-p38 MAPK activity. In addition, in NSCs from IL-1 deficient mice, DHA significantly increased proliferation without effects on p-P38 MAPK, suggesting effects of DHA are mediated via alternative signalling pathways. These results provide crucial new insights into the divergent effects of EPA and DHA in regulating NSC proliferation and the pathways involved, and highlight the therapeutic potential of their interplay with endocannabinoid signalling in brain repair.

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“…DHA therefore presents the possibility of receptormediated endocytosis (RME) to overcome BBB (Chen et al, 2009). ME containing oils rich in DHA could provide the added advantage of enhanced drug delivery to brain.…”

Section: In Vivo Evaluationmentioning

confidence: 99%

Docosahexaenoic acid–mediated, targeted and sustained brain delivery of curcumin microemulsion

Shinde

Devarajan

2017

Drug Delivery

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We disclose microemulsions (ME) of curcumin (CUR) with docosahexaenoic acid (DHA)-rich oil (CUR DHA ME) for targeted delivery to the brain. MEs of CUR (5 mg/mL) with and without DHArich oil (CUR Capmul ME) suitable for intravenous and intranasal administration exhibited negative zeta potential, globule size 520 nm and good stability. Following intravenous delivery MEs exhibited high brain concentration with CUR DHA ME exhibiting a 2.8-fold higher C max than CUR solution. Furthermore, high and sustained concentration was demonstrated even at 24 h, which was 8-and 2-fold higher than CUR solution and CUR Capmul ME, respectively. Brain concentrations following intranasal administration were, however, substantially higher as evident from higher C max and AUC and sustained compared to corresponding intravenous formulations signifying nose to brain targeting. The high brain concentration of CUR DHA ME is ascribed to the targeting efficiency enabled by DHA-mediated transport across the blood-brain barrier (BBB). Histopathological and nasal toxicity confirmed safety of the MEs. Concentrationdependent cytotoxicity in vitro, on human glioblastoma U-87MG cell line was observed with CUR DHA MEs and with the blank DHA ME, implying anticancer potential of DHA. The dramatically low IC 50 value of CUR DHA ME (3.755 ± 0.24 ng/mL) is therefore attributed to the synergistic effect of CUR and DHA in the ME. The CUR concentration achieved with CUR DHA ME at 24 h which translated to 466-fold(intranasal) and 421-fold (intravenous) the IC 50 value in the U-87MG cell line suggests great promise of CUR DHA ME for therapy of brain cancer by both routes.

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Rapid β-oxidation of eicosapentaenoic acid in mouse brain: An in situ study

Cited by 134 publications

References 76 publications

RETRACTED ARTICLE: Aging decreases rate of docosahexaenoic acid synthesis-secretion from circulating unesterified α-linolenic acid by rat liver

RETRACTED ARTICLE: Aging decreases rate of docosahexaenoic acid synthesis-secretion from circulating unesterified α-linolenic acid by rat liver

Distinctive effects of eicosapentaenoic and docosahexaenoic acids in regulating neural stem cell fate are mediated via endocannabinoid signalling pathways

Docosahexaenoic acid–mediated, targeted and sustained brain delivery of curcumin microemulsion

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