Composition of plasmalogens in serum lipoproteins from patients with non-alcoholic steatohepatitis and their susceptibility to oxidation

Abstract

Plasmalogens are ether phospholipids (PL) with an alkenyl group including vinyl ether bound at the sn-1 position and a polyunsaturated fatty acid bound at the sn-2 position, and are susceptible to oxidation. To date, there are no reports on the relationship between plasmalogen in serum lipoproteins and non-alcoholic steatohepatitis (NASH), caused by multiple factors including oxidative stress. Here, we have investigated the distribution of plasmalogens in serum lipoproteins isolated from NASH patients and healthy volunteers. MethodsSerum lipoproteins were separated by gel-filtration chromatography, and analyzed for ethanolamine and choline plasmalogens using liquid chromatography-mass spectrometry. ResultsBoth plasmalogen levels were higher in HDL than in VLDL or LDL. The plasmalogens/PL ratio was significantly lower in NASH than controls, for all lipoprotein fractions. Ethanolamine plasmalogens containing 20:4 and 22:6 at the sn-2 position and choline plasmalogens containing 16:0 at the sn-1 position were 5 predominant in each group. In oxidation test using LDL from healthy serum, both types of plasmalogens were decreased during the early stages of oxidation. ConclusionPlasmalogens could be a potential biomarker for evaluating the early stages of oxidation in NASH.

The Vitamin D Receptor Regulates Glycerolipid and Phospholipid Metabolism in Human Hepatocytes

“…Indeed, the accumulation of TG could be responsible for lower plasmalogens as it has been shown that patients with NAFLD have lower total plasma plasmalogens [52]. Moreover, the plasmalogen/phospholipid ratio of any serum lipoprotein was significantly lower in patients with nonalcoholic steatohepatitis [53]. Plasmalogens are mainly synthesized in liver peroxisomes and secreted into the circulation as part of lipoproteins.…”

“…Plasmalogens are mainly synthesized in liver peroxisomes and secreted into the circulation as part of lipoproteins. The vinyl-ether double bond of plasmalogen is highly sensitive to oxidation, which allow them to act as antioxidants [53]. Therefore, the low level of plasmalogens may also be caused by oxidative stress and peroxisomal dysfunction.…”

Lipidomic signatures of post-hepatectomy liver failure using porcine hepatectomy models

“…It is well known that kidney and brain can exhibit remote organ injury from acute liver failure (34). Though the plasmalogen level in the liver is very low, the serum levels of plasmalogen in patients with mild liver inflammation or dysfunction such as nonalcoholic steatohepatitis were significantly decreased in comparison to those of healthy controls, which could be due to peroxisomal dysfunction and/or impaired hepatic biosynthesis of plasmalogens (35). In contrast, kidney and brain contain high levels of plasmalogen and are easily injured in the setting of acute liver failure suggesting that high levels of plasmalogen in the serum of the 90% PH group could originate from the remote injury in kidney or brain.…”

Recent progress in the LC–MS/MS analysis of oxidative stress biomarkers

“…Recently, Ikuta et al. developed an analytical method for the analysis of both ethanolamine plasmalogen and choline plasmalogen of serum lipoproteins in healthy controls and in patients with non‐alcoholic steatohepatitis [201]. Before analysis, the serum samples were subjected to gel filtration chromatography as previously reported [202].…”