Age-related increase in LDL-cholesterol is associated with enhanced oxidative stress and disturbed sphingolipid metabolism

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• 作者：Saem Jung ; Minjoo Kim ; Hyo Jeong Ryu ; Jey Sook Chae ; Sang-Hyun Lee…
• 关键词：Sphingomyelin ; C17 sphinganine ; Lactosylceramide ; Phosphatidylcholine ; Lysophosphatidylcholine ; Oxidative stress
• 刊名：Metabolomics
• 出版年：2015
• 出版时间：February 2015
• 年：2015
• 卷：11
• 期：1
• 页码：40-49
• 全文大小：377 KB
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• 刊物主题：Biochemistry, general; Molecular Medicine; Cell Biology; Developmental Biology; Biomedicine general;
• 出版者：Springer US
• ISSN：1573-3890

文摘

We investigated alterations in plasma metabolites associated with the age-related increase in circulating concentration of low-density lipoprotein (LDL)-cholesterol. The study included 602 healthy, nondiabetic subjects (aged 30-5?years). Among 393 individuals with LDL-cholesterol within the normal limit at baseline, 56 (14.2?%) developed high fasting LDL-cholesterol levels after 3?years. The 337 subjects that retained normal LDL-cholesterol were matched for age, gender, BMI, and fasting LDL-cholesterol to form the control group (n?=?78). At the 3-year follow-up, the high-LDL group showed greater increases in serum total-cholesterol and LDL-cholesterol, plasma oxidized LDL, lipoprotein-associated phospholipase A2 activity, and urinary 8-epi-prostaglandin F2α than the control group after adjusting for baseline levels. The high-LDL group also showed significant decreases in sphingomyelin (SM) (d18:0/16:1) and phosphatidylcholine (PC) (18:0/20:4), which were associated with an increases on LDL-cholesterol, and significant increases in palmitic amide and lactosylceramide. Mean changes in the levels of SM (d18:0/16:1), C17 sphinganine, PC (18:0/20:4), and eight lysoPCs containing C16:1, C16:0, C17:0, C18:1, C18:0, C20:4, C20:3, and C22:6 were statistically different between control and high-LDL groups. Overall, the change in ox-LDL positively correlated with changes in LDL-cholesterol, Lp-PLA2 activity, palmitic amide, oleamide, lysoPCs, and C17 sphinganine, and negatively correlated with changes in SM (d18:0/16:1) (r?=??.501, P?