Short-term supplementation of EPA-enriched ethanolamine plasmalogen increases the level of DHA in the brain and liver of n-3 PUFA deficient mice in early life after weaning

A lack of n-3 polyunsaturated fatty acids (PUFAs) in mothers’ diet significantly reduced the amount of docosahexaenoic acid (DHA) in the brains of offspring, which might affect their brain function. Our previous research has proven multiple benefits of eicosapentaenoic acid (EPA)-enriched ethanolamine plasmalogen (pPE) in enhancing the learning and memory ability. However, the effect of dietary supplementation with EPA-pPE on the DHA content in the brain and liver of offspring lacking n-3 PUFAs in early life is still unclear.

Female ICR mice were fed with n-3 PUFA-deficient diets throughout the gestation and lactation periods to get n-3 PUFA-deficient offspring.

The lipid profiles in the cerebral cortex and liver of offspring were analyzed using lipidomics after dietary supplementation with EPA-pPE (0.05%, w/w) and EPA-phosphatidylcholine (PC) (0.05%, w/w) for 2 weeks after weaning. Dietary supplementation with EPA could significantly change fatty acid composition in a variety of phospholipid molecular species compared with the n-3 deficient group. EPA-pPE and EPA-PC remarkably increased the DHA content in the brain PC, ether-linked phosphatidylcholine (ePC), and phosphatidylethanolamine plasmalogen (pPE) and liver triglyceride (TG), lyso-phosphatidylcholine (LPC), ePC, phosphatidylethanolamine (PE), and pPE molecular species, in which EPA-pPE showed more significant effects on the increase of DHA in cerebral cortex PC, ePC and liver PC compared with EPA-PC. Both EPA-phospholipids could effectively increase the DHA levels, and the pPE form was superior to PC in the contribution of DHA content in the cerebral cortex PC, ePC and liver PC molecular species. EPA-enriched ethanolamine plasmalogen might be a good nutritional supplement to increase DHA levels in the brains of n-3 PUFA-deficient offspring.

Eleven racemic ethanolamine derivatives were prepared, and their enantiomers were separated using liquid chromatography with various chiral columns. These derivatives included chiral vicinal amino alcohols, β-hydroxy ureas, β-hydroxy thioureas, and β-hydroxy guanidines, all of which are present in many active pharmaceutical ingredients. The screening study was performed with six chiral stationary phase containing columns, including four recently introduced superficially porous particles bonded with two macrocyclic glycopeptides, a cyclodextrin derivative and a cyclofructan derivative. The two remaining columns contained chiral stationary phases, based on either a cellulose derivative or derivatized amylose, both bonded to fully porous particles. The cyclodextrin and cellulose-based chiral stationary phases proved to be the most broadly effective selectors and were able to separate 8 and 7 of the 11 tested compounds, respectively. With respect to analyte structural features, marked differences in enantiorecognition were observed between compounds containing phenyl and cyclohexyl groups adjacent to the stereogenic center. Additionally, replacing a small electronegative oxygen atom by a larger and less electronegative sulfur atom induced a significant difference in chiral recognition by the cellulose derivative as well as by the vancomycin-based chiral selectors.

Glycosylphosphatidylinositol (GPI)-anchored proteins play important roles in maintaining the function of the cell wall and participating in pathogenic processes. The addition and removal of phosphoethanolamine (EtN-P) on the second mannose residue in the GPI anchor are vital for maturation and sorting of GPI-anchored proteins. Previously, we have shown that deletion of the gpi7, the gene that encodes an EtN-P transferase responsible for the addition of EtN-P to the second mannose residue of the GPI anchor, leads to the mislocalization of GPI-anchored proteins, abnormal polarity, reduced conidiation, and fast germination in Aspergillus fumigatus. In this report, the adherence and virulence of the A. fumigatus gpi7 deletion mutant were further investigated.

The germinating conidia of the mutant exhibited an increased adhesion and a higher exposure of cell wall polysaccharides. Although the virulence was not affected, an increased adherence and a stronger inflammation response of the mutant were documented in an immunocompromised mouse model. An in vitro assay confirmed that the Δgpi7 mutant induced a stronger immune response and was more resistant to killing.

Our findings, for the first time, demonstrate that in A. fumigatus, GPI anchoring is required for proper organization of the conidial cell wall. The lack of Gpi7 leads to fast germination, stronger immune response, and resistance to macrophage killing.