Structural changes of ethanolamine plasmalogen during intestinal absorption

Takahashi T, Kamiyoshihara R, Otoki Y, Kato S, Suzuki T, Yamashita S, Eitsuka T, Ikeda I, and Nakagawa K. (2020) Structural changes of ethanolamine plasmalogen during intestinal absorption. Food and Function

Plasmalogens are a class of phospholipids that contain a glycerol backbone with a vinyl-ether bond connecting a fatty alcohol at sn-1, an acyl-linked fatty acid at sn-2, and either an ethanolamine or choline head group at sn-3. Unique to this class is the vinyl-ether bond, which confers the unique biological functionality of plasmalogens. This double bond causes the side chains at sn-1 and sn-2 to have a parallel alignment, producing a more compact structure. This conformation causes plasmalogens to play a critical role in membrane structure and vesicular fusion. In addition, the vinyl bond can scavenge two radical oxygen species (ROS), giving plasmalogens antioxidant properties. A reduction in this class of phospholipids is associated with Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and Autism spectrum disorders. In extreme cases, a complete deficiency in plasmalogens due to genetic mutations in the proteins involved in their synthesis results in a severe form of dwarfism with cognitive deficits called rhizomelic chondrodysplasia punctata (RCDP). Takahashi et al investigated how ethanolamine plasmalogens (PlsEtns) are absorbed and altered during absorption using the lymph-cannulation method and everted jejunal sac model in rats.

To determine the absorption of each species of plasmalogens the lympho-cannulation method was utilized, allowing the lymph, fluid that contains white blood cells and drains through the lymphatic system including the interstitial space between cells in all body tissues, to be collected after administering a lipid emulsion into the stomach of the rats. As the lipid profile of the emulsion is known, this enabled the plasmalogen species absorption to be determined over time. A “blank” lymph sample taken from fasted animals had undetectable plasmalogen levels, while following treatment with the lipid emulsion PlsEtns 18:0/18:1, 18:0/20:4, and 18:0/22:6 were clearly elevated with the maximum measurements reached at 2 hours. Although the lipid emulsion contained almost 20x the levels of 18:0/22:6 compared to 18:0/20:4, the levels found in the lymph were similar at ~100-130 nmol. Interestingly, choline plasmalogens (PlsCho) 18:0/20:4 were detected in the lymph, although PlsCho were not a part of the initial emulsion. These results indicate that the vinyl-ether bond present in the plasmalogens does not inhibit their ability to be absorbed by the body, confirming previous work done by MLD, and that the lipids are remodeled during absorption.

To analyze the intestinal absorption profiles, the everted jejunal sac model was utilized by removing the intestines of fasted rats, cutting the proximal jejunum into 2 cm segments, and removing the adhering fat before tying the ends of the segment and everting it, forming a sac. After the sacs had been filled with an oxygenated nutrient solution and bathed in mucosal fluid, the mucosal fluid from the sac and the tissue homogenates was extracted. Similarly with lymph fluid, the tissues that had been incubated in mucosal fluid showed significantly higher levels of PlsEtns compared to the blank group with an increase in PlsEtn 18:0/20:4 from 125 to 160 pmol/mg of wet tissue and 18:0/22:6 from 35 to 55 pmol/mg of wet tissue. This could indicate that plasmalogens within the mucosal fluid were absorbed into the intestinal tissues. PlsEtn 18:0/20:4 was found in high levels again although not being the predominant component of the emulsion and thus mucosal fluid, agreeing with the previous experiment that there are modifications to the lipids during absorption. Similarly, PlsCho were also seen within the intestinal tissues, although not being present within the mucosal fluid, supporting the findings of the previous experiment that the plasmalogens are modified during absorption.

Takahashi et al have demonstrated that although plasmalogens contain a potentially unstable double bond, these lipids are still able to be taken up by the intestinal mucosa in rats. As many disorders are associated with a plasmalogen deficiency, this research indicates that treatment with plasmalogens will be able to be taken up by the intestine, enter the lymph, and have the potential to be incorporated by the body. As well, it was shown that there are some structural alterations made to lipids as they are absorbed and is the first study to show this modification by the intestinal mucosa. Takahashi et al suggest that this conversion could be to conserve docosahexaenoic acid (DHA), which is known to aid in brain function and thought to reduce the risk of Alzheimer’s disease, by cleaving this chain and replacing it with arachidonic acid. Future work looking at PlsEtn treatments and the plasmalogen species they are converted to could provide more answers on their physiological functions in vivo.