Abstract
BackgroundPlasmalogens are ether phospholipids required for normal mammalian developmental, physiological, and cognitive functions. They have been proposed to act as membrane antioxidants and reservoirs of polyunsaturated fatty acids as well as influence intracellular signaling and membrane dynamics. Plasmalogens are particularly enriched in cells and tissues of the human nervous, immune, and cardiovascular systems. Humans with severely reduced plasmalogen levels have reduced life spans, abnormal neurological development, skeletal dysplasia, impaired respiration, and cataracts. Plasmalogen deficiency is also found in the brain tissue of individuals with Alzheimer disease.ResultsIn a human and great ape cohort, we measured the red blood cell (RBC) levels of the most abundant types of plasmalogens. Total RBC plasmalogen levels were lower in humans than bonobos, chimpanzees, and gorillas, but higher than orangutans. There were especially pronounced cross-species differences in the levels of plasmalogens with a C16:0 moiety at the sn-1 position. Humans on Western or vegan diets had comparable total RBC plasmalogen levels, but the latter group showed moderately higher levels of plasmalogens with a C18:1 moiety at the sn-1 position. We did not find robust sex-specific differences in human or chimpanzee RBC plasmalogen levels or composition. Furthermore, human and great ape skin fibroblasts showed only modest differences in peroxisomal plasmalogen biosynthetic activity. Human and chimpanzee microarray data indicated that genes involved in plasmalogen biosynthesis show cross-species differential expression in multiple tissues.ConclusionWe propose that the observed differences in human and great ape RBC plasmalogens are primarily caused by their rates of biosynthesis and/or turnover. Gene expression data raise the possibility that other human and great ape cells and tissues differ in plasmalogen levels. Based on the phenotypes of humans and rodents with plasmalogen disorders, we propose that cross-species differences in tissue plasmalogen levels could influence organ functions and processes ranging from cognition to reproduction to aging.
Highlights
Plasmalogens are ether phospholipids required for normal mammalian developmental, physiological, and cognitive functions
red blood cell (RBC) plasmalogen levels are used in diagnostic tests for human disorders involving impaired plasmalogen biosynthesis [64,65]
Human and great ape RBC plasmalogen levels Total RBC plasmalogen levels differed in the human Western diet (WD) and vegan groups relative to the great apes (ANOVA P < 1 × 10-4 for both comparisons) (Figure 4)
Summary
Plasmalogens are ether phospholipids required for normal mammalian developmental, physiological, and cognitive functions. In agreement with phylogenetic relationships [6,7,8,9], human blood lipid profiles most closely resemble those of their closest living relatives, the great apes They comprise about 20% of the phospholipid mass in humans and chemically differ from more abundant glycerophospholipids as well as other ether phospholipids by the presence of a vinyl ether bond at the sn-1. Decreased brain tissue plasmalogen levels have been associated with Alzheimer Disease [48,49,50,51,52,53,54,55], X-linked adrenoleukodystrophy [56,57], and Down syndrome [58]
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