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

Saem Jung, Minjoo Kim, Hyo Jeong Ryu, Jey Sook Chae, Sang Hyun Lee, Jong Ho Lee

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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 30–65 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 F 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 = −0.501, P < 0.001). An age-related increase in LDL-cholesterol is associated with enhanced oxidative stress and disturbed sphingolipid metabolism.

Original languageEnglish
Pages (from-to)40-49
Number of pages10
JournalMetabolomics
Volume11
Issue number1
DOIs
Publication statusPublished - 2014 Jan 1

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Sphingolipids
Oxidative stress
Metabolism
LDL Cholesterol
Oxidative Stress
LDL Lipoproteins
Sphingomyelins
HDL Lipoproteins
1-Alkyl-2-acetylglycerophosphocholine Esterase
Phosphatidylcholines
Amides
Fasting
Plasmas
Control Groups
Dinoprost
Cholesterol
Metabolites
Healthy Volunteers

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Clinical Biochemistry

Cite this

Jung, Saem ; Kim, Minjoo ; Ryu, Hyo Jeong ; Chae, Jey Sook ; Lee, Sang Hyun ; Lee, Jong Ho. / Age-related increase in LDL-cholesterol is associated with enhanced oxidative stress and disturbed sphingolipid metabolism. In: Metabolomics. 2014 ; Vol. 11, No. 1. pp. 40-49.
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abstract = "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 30–65 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 = −0.501, P < 0.001). An age-related increase in LDL-cholesterol is associated with enhanced oxidative stress and disturbed sphingolipid metabolism.",
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Age-related increase in LDL-cholesterol is associated with enhanced oxidative stress and disturbed sphingolipid metabolism. / Jung, Saem; Kim, Minjoo; Ryu, Hyo Jeong; Chae, Jey Sook; Lee, Sang Hyun; Lee, Jong Ho.

In: Metabolomics, Vol. 11, No. 1, 01.01.2014, p. 40-49.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Age-related increase in LDL-cholesterol is associated with enhanced oxidative stress and disturbed sphingolipid metabolism

AU - Jung, Saem

AU - Kim, Minjoo

AU - Ryu, Hyo Jeong

AU - Chae, Jey Sook

AU - Lee, Sang Hyun

AU - Lee, Jong Ho

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N2 - 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 30–65 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 = −0.501, P < 0.001). An age-related increase in LDL-cholesterol is associated with enhanced oxidative stress and disturbed sphingolipid metabolism.

AB - 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 30–65 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 = −0.501, P < 0.001). An age-related increase in LDL-cholesterol is associated with enhanced oxidative stress and disturbed sphingolipid metabolism.

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