Differential lipid metabolism in monocytes and macrophages: Influence of cholesterol loading

Irene Fernandez-Ruiz, Patrycja Puchalska, Chandrakala Aluganti Narasimhulu, Bhaswati Sengupta, Sampath Parthasarathy

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

The influence of the hypercholesterolemia associated with atherosclerosis on monocytes is poorly understood. Monocytes are exposed to high concentrations of lipids, particularly cholesterol and lysophosphatidylcholine (lyso-PC). Indeed, in line with recent reports, we found that monocytes accumulate cholesteryl esters (CEs) in hypercholesterolemic mice, demonstrating the need for studies that analyze the effects of lipid accumulation on monocytes. Here we analyze the effects of cholesterol and lyso-PC loading in human monocytes and macrophages. We found that cholesterol acyltransferase and CE hydrolase activities are lower in monocytes. Monocytes also showed a different expression profile of cholesterol influx and efflux genes in response to lipid loading and a different pattern of lyso-PC metabolism. In monocytes, increased levels of CE slowed the conversion of lyso-PC into PC. Interestingly, although macrophages accumulated glycerophosphocholine, phosphocholine was the main water-soluble choline metabolite being generated in monocytes, suggesting a role for monoand diacylglycerol in the chemoattractability of these cells. In summary, monocytes and macrophages show significant differences in lipid metabolism and gene expression profiles in response to lipid loading. These findings provide new insights into the mechanisms of atherosclerosis and suggest potentials for targeting monocyte chemotactic properties not only in atherosclerosis but also in other diseases.

Original languageEnglish (US)
Pages (from-to)574-586
Number of pages13
JournalJournal of lipid research
Volume57
Issue number4
DOIs
StatePublished - Apr 2016
Externally publishedYes

Bibliographical note

Publisher Copyright:
Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.

Keywords

  • Dyslipidemias
  • Foam cells
  • Glycerophosphocholine
  • Lysophosphatidylcholine
  • Lysophospholipid
  • Phosphocholine
  • Supplementary key words atherosclerosis

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