The human liver lipidome is significantly related to the lipid composition and aggregation susceptibility of low-density lipoprotein (LDL) particles

Elsevier

Available online 23 November 2022

AtherosclerosisAuthor links open overlay panelHighlights•

Fatty acid composition of major lipid species in human LDL particles closely resembles those of the liver.

Hepatic dihydroceramides and ceramides are related to sphingomyelin-rich aggregation-prone LDL particles.

Lipid composition of the human liver may influence atherogenesis.

AbstractBackground and aims

The susceptibility of low-density lipoprotein (LDL) to aggregation predicts atherosclerotic cardiovascular disease. However, causes of interindividual variation in LDL lipid composition and aggregation susceptibility remain unclear. We examined whether the lipid composition and aggregation susceptibility of LDL reflect the lipid composition of the human liver.

Methods

Liver biopsies and blood samples for isolation of LDL particles were obtained from 40 obese subjects (BMI 45.9 ± 6.1 kg/m2, age 43 ± 8 years). LDL was isolated using sequential ultracentrifugation and lipidomic analyses of liver and LDL samples were determined using ultra-high performance liquid chromatography–mass spectrometry. LDL aggregation susceptibility ex vivo was analyzed by inducing aggregation by human recombinant secretory sphingomyelinase and following aggregate formation.

Results

The composition (acyl carbon number and double bond count) of hepatic triglycerides, phosphatidylcholines, and sphingomyelins (SMs) was closely associated with that of LDL particles. Hepatic dihydroceramides and ceramides were positively correlated with concentrations of the corresponding SM species in LDL as well with LDL aggregation. These relationships remained statistically significant after adjustment for age, sex, and body mass index.

Conclusions

Lipid composition of LDL reflects that of the human liver in obese patients. Changes in hepatic sphingolipid metabolism may contribute to interindividual variation of LDL lipid composition and susceptibility to aggregation.

Keywords

Atherosclerosis

Cardiovascular disease

Ceramides

Cholesterol

Lipidomics

Phosphatidylcholines

Triglycerides

© 2022 The Authors. Published by Elsevier B.V.

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