Lipids Signaling

Author: Gianpiero Pescarmona
Date: 04/04/2019


Docosahexaenoic acid (DHA) is an omega-3 fatty acid that is a primary structural component of the human brain, cerebral cortex, skin, and retina. In physiological literature, it is given the name 22:6(n-3). It can be synthesized from alpha-linolenic acid or obtained directly from maternal milk (breast milk), fish oil, or algae oil.








Resolvins are a family of n-3 lipid mediators initially identified in resolving inflammatory exudates that temper inflammatory responses to promote catabasis. Here, temporal metabololipidomics with selflimited resolving exudates revealed that resolvin (Rv) D3 has a distinct time frame from other lipid mediators, appearing late in the resolution phase. Using synthetic materials prepared by stereocontrolled total organic synthesis and metabololipidomics, we established complete stereochemistry of RvD3 and its aspirin-triggered 17R-epimer (ATRvD3). Both synthetic resolvins potently regulated neutrophils and mediators, reducing murine peritonitis and dermal inflammation. RvD3 and AT-RvD3 displayed leukocyte-directed actions, e.g., blocking human neutrophil transmigration and enhancing macrophage phagocytosis and efferocytosis. These results position RvD3 uniquely within the inflammation-resolution time frame to vantage and contribute to the beneficial actions of aspirin and essential n-3 fatty acids.

Resolvin D3 and Aspirin-Triggered Resolvin D3 Are Potent Immunoresolvents


2019-04-04T13:50:48 - Annamaria Vernone

J Stein Brain Sciences 2018 What is Developmental Dyslexia?

The high dynamic sensitivity of magnocellular neurons necessitates high membrane flexibility so that their ionic channels can open and close very fast. This flexibility is provided by their local lipid environment, particularly by the incorporation into the membrane of one very important omega 3 long chain fatty acid, Docosahexaenoic acid (DHA) [77,78]. This provides exactly the right physical and electrostatic properties for their membranes to allow optimum dynamic performance of the ionic channels passing through them [79].

Dyslexic children tend to have very low levels of DHA in their blood, and the degree of their blood DHA deficit predicts the magnitude of their reading deficit. Hence, we have found that supplementing the diet of dyslexic children with DHA can often help them to improve their reading, sometimes dramatically [80,81,82]. These observations all reaffirm the importance of magnocellular function for reading.

J Stein 2016 Nutrients. 2016 Docosahexaenoic Acid and Cognition throughout the Lifespan

Another consideration is the use of other supplements in boosting the effects of DHA, or acting in synergy, especially with regards to aging. For example, curcumin can boost DHA levels in the brain of animals [330], and it is intriguing to speculate that curcumin could help mitigate the losses in DHA that are associated with the heightened β-oxidation that is observed in AD. As previously mentioned, B vitamins and DHA work in tandem to reduce brain atrophy in MCI patients [134]. B vitamins lower Hcy, an intermediate in some oxidative stress-related pathways that are a risk factor for vascular disease as well as dementia. Hcy can also serve as notification that pathological neurodegenerative processes are occurring. Additionally, B vitamins may promote DHA incorporation into phospholipids, and likely have synergistic anti-inflammatory effects. In support of a combinatorial approach, Scheltens et al. [331] observed improvements in memory after daily supplementation with DHA, EPA, phospholipids, choline, uridine monophosphate, vitamin E, vitamin C, selenium, folic acid, vitamin B6, and vitamin B12 for 24 weeks in subjects with mild AD (Alzheimer's disease).

The non-steroidal anti-inflammatory drug (NSAID) aspirin might be another potential synergistic agent. Acetylation by aspirin enables COX-2 to initiate the biosynthetic pathway that produces resolvins (D1–D6) from DHA [332,333]. Aspirin-dependent resolvins are potent DHA-derived pro-resolving immune mediators [334]. Resolvin D3 has been shown to be especially effective in the late-resolving phase of inflammation (catabasis), the completion of which is critical to prevent an acute inflammatory response from becoming chronic activation [335]. The use of NSAIDs has been associated with a reduced risk for AD, especially in long-time users [336,337]. However, these effects are not realized in currently diagnosed AD, highlighting the likely importance of preventative supplementation [338].

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