Synthesis and Biological Interest of Structured Docosahexaenoic Acid-Containing Triacylglycerols and Phospholipids

International audienceAbstract: In light of rapid progress in biochemistry and modern bioengineering, there is a great interest in understanding how modifying the structure of naturally occurring lipids can be used to improve their nutritional and health properties. Structured lipids (SLs) or custom-made lipids can supply functional fatty acids because of their specific positioning in the glycerol structure. Health benefits of n-3 fatty acids such as docosahexaenoic acid (DHA) have been widely reported. Little information is available on the potential for health benefits of the SLs molecules that are rich in DHA and have well defined structure.This review attempts to summarize our present state of knowledge of various approaches to produce structured DHA-containing triglycerides and phospholipids as well as their applications

AceDoPC, a structured phospholipid to target the brain with docosahexaenoic acid

AceDoPC® is a structured phospholipid or acetyl-LysoPC-DHA made to prevent docosahexaenoic acyl migrating from the sn-2 to sn-1 position of the phospholipid, however keeping the main physical-chemical properties of LysoPC-DHA. As previously shown for LysoPC-DHA, AceDoPC® allows DHA crossing a re-constituted blood-brain barrier with higher efficiency than non-esterified DHA or PC-DHA. When injected to blood of rats, AceDoPC® is processed within the brain to deliver DHA to phosphatidyl-choline and -ethanolamine. When injected to rats following the induction of an ischemic stroke, AceDoPC® prevents the extension of brain lesions more efficiently than DHA. Overall, these properties make AceDoPC® a promising phospholipid carrier of DHA to the brain

AceDoPC, a structured phospholipid to target the brain with docosahexaenoic acid

International audienceAceDoPCr (R) is a structured phospholipid or acetyl-LysoPC-DHA made to prevent docosahexaenoic acyl migrating from the sn-2 to sn-1 position of the phospholipid, however keeping the main physical-chemical properties of LysoPC-DHA. As previously shown for LysoPC-DHA, AceDoPCr (R) allows DHA crossing a re-constituted blood-brain barrier with higher efficiency than non-esterified DHA or PC-DHA. When injected to blood of rats, AceDoPCr (R) is processed within the brain to deliver DHA to phosphatidyl-choline and -ethanolamine. When injected to rats following the induction of an ischemic stroke, AceDoPCr (R) prevents the extension of brain lesions more efficiently than DHA. Overall, these properties make AceDoPCr (R) a promising phospholipid carrier of DHA to the brain

Specific uptake of DHA by the brain from a structured phospholipid, AceDoPC((R))

International audienceDocosahexaenoic acid (DHA; 22: 6 omega-3) is highly enriched in the brain and is required for proper brain development and function. Its deficiency has been shown to be linked with the emergence of neurological diseases. Dietary omega-3 fatty acid supplements including DHA have been suggested to improve neuronal development and enhance cognitive functions. Findings suggested that DHA is better incorporated into the brain when esterified at the sn-2 position of a lysophosphatidylcholine (LysoPC-DHA). AceDoPC (R) is a structured phospholipid or acetyl-LysoPC-DHA. As previously shown for LysoPC-DHA, AceDoPC (R) is a specific and preferred carrier of DHA to the brain. When AceDoPC (R) was injected to rats that were subjected to an ischemic stroke, it prevents the extension of brain lesions. Regarding the essential role of DHA for cerebral functions, targeting the brain with specific carriers of DHA might provide novel therapeutic approaches to neurodegenerative diseases

Biological properties of a DHA-containing structured phospholipid (AceDoPC) to target the brain.

International audience: 1-acetyl,2-docosahexaenoyl-glycerophosphocholine (AceDoPC) has been made to prevent docosahexaenoyl (DHA) to move to the sn-1 position as it rapidly does when present in 1-lyso,2-docosahexaenoyl-GPC (lysoPC-DHA), an efficient DHA transporter to the brain. When incubated with human blood, AceDoPC behaves closer to lysoPC-DHA than PC-DHA in terms of binding to plasma albumin and lipoproteins, and DHA incorporation into platelets and red cells. In addition, AceDoPC prevents more efficiently the deleterious effects of the experimental stroke in rats than does unesterified DHA. Also, AceDoPC inhibits platelet-activating factor-induced human blood platelet aggregation. Overall, AceDoPC might act as an efficient DHA transporter to the brain, and as a neuro-protective agent by itself

Brain targeting with docosahexaenoic acid as a prospective therapy for neurodegenerative diseases and its passage across blood brain barrier

International audienceDocosahexaenoic acid (DHA, 22:6n-3) is the main omega-3 polyunsaturated fatty acid in brain tissues necessary for common brain growth and function. DHA can be provided to the body through two origins: an exogenous origin, from direct dietary intakes and an endogenous one, from the bioconversion of the essential a-linolenic acid (ALA, 18:3n-3) in the liver. In humans, the biosynthesis of DHA from its precursor ALA is very low. A reduction in the cerebral amount of DHA is detected in patients suffering from neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Considering the vital functions of DHA for the brain, new methodologies to target the brain with DHA offers encouraging perceptions in the improvement of precautionary and therapeutic approaches for neurodegenerative diseases. The aim of the present review was to provide better understanding of the cerebral uptake of DHA in different form including free fatty acids, Lysophosphatidylcholines LysoPC-DHA as well as structured phospholipids. First, we explored the special structure of the blood-brain barrier BBB, BBB being a physical and metabolic barrier with restrictive properties. Then, we discussed the incorporation of DHA into the membrane phospholipids of the brain, the neuroprotective and therapeutic effect of DHA for neurological diseases. (C) 2020 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM)

Synthesis and Identification of AceDoxyPC, a Protectin-Containing Structured Phospholipid, Using Liquid Chromatography/Mass Spectrometry

International audienceFatty acids have many health benefits in a great variety of diseases ranging from cardiovascular to cerebral diseases. For instance, docosahexaenoic acid (DHA), which is highly enriched in brain phospholipids, plays a major role in anti-inflammatory or neuroprotective pathways. Its effects are thought to be due, in part, to its conversion into derived mediators such as protectins. 1-Lyso,2-docosahexaenoyl-glycerophosphocholine (LysoPtdCho-DHA) is one of the physiological carrier of DHA to the brain. We previously synthesized a structured phosphatidylcholine to mimic 1-lyso,2-docosahexaenoyl-glycerophosphocholine, named AceDoPC(A (R)) (1-acetyl,2-docosahexaenoyl-glycerophosphocholine), that is considered as a stabilized form of the physiological LysoPtdCho-DHA and that is neuroprotective in experimental ischemic stroke. Considering these, the current study aimed at enzymatically oxygenate DHA contained within AceDoPC(A (R)) to synthesize a readily structured oxidized phospholipid containing protectin DX (PDX), thereafter named AceDoxyPC (1-acetyl,2-PDX-glycerophosphocholine). Identification of this product was performed using liquid chromatography/tandem mass spectrometry. Such molecule could be used as a bioactive mediator for therapy against neurodegenerative diseases and stroke

Mechanisms of DHA transport to the brain and potential therapy to neurodegenerative diseases

Docosahexaenoic acid (DHA; 22:6 omega-3) is highly enriched in the brain and is required for proper brain development and function. Its deficiency has been shown to be linked with the emergence of neurological diseases. Dietary omega-3 fatty acid supplements including DHA have been suggested to improve neuronal development and enhance cognitive functions. However, mechanisms of DHA incorporation in the brain remain to be fully understood. Findings suggested that DHA is better incorporated when esterified within lysophospholipid rather than under its non-esterified form. Furthermore, DHA has the potential to be converted into diverse oxylipins with potential neuroprotective effects. Since DHA is poorly synthesized de novo, targeting the brain with specific carriers of DHA might provide novel therapeutic approaches to neurodegenerative diseases

The pleiotropic effects of omega-3 docosahexaenoic acid on the hallmarks of Alzheimer's disease

Among omega-3 polyunsaturated fatty acids (PUFAs), docosahexaenoic acid (DHA, 22:6n-3) is important for adequate brain development and cognition. DHA is highly concentrated in the brain and plays an essential role in brain functioning. DHA, one of the major constituents in fish fats, readily crosses the blood brain barrier from blood to the brain. Its critical role was further supported by its reduced levels in the brain of Alzheimer's disease (AD) patients. This agrees with a potential role of DHA in memory, learning and cognitive processes. Since there is yet no cure for dementia such as AD, there is growing interest in the role of DHA-supplemented diet in the prevention of AD pathogenesis. Accordingly, animal, epidemiological, preclinical and clinical studies indicated that DHA has neuroprotective effects in a number of neurodegenerative conditions including AD. The beneficial effects of this key omega-3 fatty acid supplementation may depend on the stage of disease progression, other dietary mediators and the apolipoprotein ApoE genotype. Herein, our review investigates, from animal and cell culture studies, the molecular mechanisms involved in the neuroprotective potential of DHA with emphasis on AD