Myo-Inositol Treatment Increases Serum Plasmalogens and Decreases Small Dense LDL, Particularly in Hyperlipidemic Subjects with Metabolic Syndrome

Abstract

Summary Background and aim: We have previously shown that serum plasmalogen levels positively correlate with HDL, and significantly decrease with aging, and may be related to LDL particle size. The objective of the present study was to investigate the effects of increased serum plasmalogens on lipidosis, particularly the appearance of atherogenic small dense LDL (sdLDL), of subjects with hyperlipidemia and metabolic syndrome (MetS). Methods and results: The effects of increased serum plasmalogen levels, induced by 2 wk of myoinositol treatment, on several clinical and biochemical parameters were examined in 17 hyperlipidemic subjects including some with MetS. After myo -inositol treatment, significant increases in plasmalogen-related parameters, particularly ChoPlas, and significant decreases in atherogenic cholesterols including sdLDL, were observed. Among the hyperlipidemic subjects treated with myo -inositol, compared to subjects without MetS, subjects with MetS had a significant increase in plasmalogens and a tendency towards reduced sdLDL, high sensitivity C-reactive protein (hsCRP), and blood glucose levels. Correlation analyses between the measured parameters showed that plasmalogens, as well as HDL, function as beneficial factors, and that sdLDL is a very important risk factor that shows positive correlations with many other risk factors. Conclusion: These results suggest that increased plasmalogen biosynthesis and/or serum levels are especially effective in improving MetS among hyperlipidemic subjects with MetS. Key Words plasmalogens, metabolic syndrome, small dense low-density lipoprotein, myoinositol Plasmalogens (1-alkenyl-2-acyl-sn -glycero-3-phospholipids) in serum are biosynthesized in the liver and secreted into circulating blood as lipoprotein components. Several studies have shown that plasmalogen levels in the plasma or red blood cell membranes decrease with aging or in the presence of hyperlipidemia ( 1 ); plasmalogen levels are decreased in the lowdensity lipoprotein (LDL) of familial hypercholesterolemia patients ( 2 ). However, large scale clinical studies have not yet been done, because the conventional methods used to determine plasmalogens are laborious and unsuitable for highly sensitive quantification.Recently, we established a highly sensitive and convenient method for quantifying choline plasmalogen (ChoPlas) and ethanolamine plasmalogen (EtnPlas) separately ( 3 ). Using this new method, we quantified the serum plasmalogen levels of approximately 300 subjects, and analyzed the correlations of serum plasmalogens with clinical markers and serum biochemical markers. The following results were obtained: i) serum plasmalogens decrease markedly with aging; ii) serum plasmalogen levels are positively correlated with highdensity lipoprotein (HDL); and iii) the ratio of ChoPlas to EtnPlas is positively correlated with LDL particle size ( 4 ). These results suggest that serum plasmalogens, as well as HDL, function as beneficial factors, and furthermore that plasmalogen biosynthesis and/or se...

The Proportion of Nervonic Acid in Serum Lipids is Associated with Serum Plasmalogen Levels and Metabolic Syndrome

“…Similarly to C22:0, C24:0 and C24:1, serum levels of PlsCho and the resultant PlsCho/PlsEtn and PlsCho/PL ratios of MetS subjects were significantly reduced compared to non-MetS subjects Table 3 . This result is in agreement with our previous study, in which hyperlipidemic subjects with MetS showed a considerable reduction in serum levels of both classes of plasmalogens compared to those without MetS 37 . In addition, these VLCFAs as well as C20:4 in serum lipids showed a significant positive correlation, particularly with PlsCho-related parameters Table 5 .…”

Improvement and validation of 125I-high-performance liquid chromatography method for determination of total human serum choline and ethanolamine plasmalogens

“…These diseases are often substantially deficient in Pls, because part of Pls' biosynthetic enzymes are localized in this organelle. 2 Recently, serum (or plasma) Pls have gained interest in several clinical symptoms such as metabolic syndrome/atherosclerosis 3,4 or Alzheimer's disease 5 other than peroxisomal disorders.…”

Extrinsic effectors regulating genes for plasmalogen biosynthetic enzymes in HepG2 cells

“…Monounsaturated long-chain fatty acids such as oleic acid (C18:1) and erucic acid (C22:1), myo-inositol, and Pl precursors, alkylglycerol and HG, have been reported to increase Pl levels in laboratory animals and humans [19][20][21][22][23]. However, they unexpectedly reduced the gene expression of Pl biosynthetic enzymes in HepG2 cells (Table 2).…”

“…Accordingly, we attempted to increase the levels of plasma Pls as a preventative strategy for diseases associated with oxidative stress and aging. This was achieved in laboratory animals as well as humans through administration of the Pl precursor alkylglycerol [19], myoinositol (MI) [20,21], monounsaturated long-chain fatty acids [22], and the hypolipidemic agent, statin [23]. However, their effects on the gene expression of Pl biosynthetic enzymes remain unknown.…”