Macrophage 12/15 lipoxygenase expression increases plasma and hepatic lipid levels and exacerbates atherosclerosis

Shunxing Rong, Qiang Cao, Mingxia Liu, Jeongmin Seo, Lin Jia, Elena Boudyguina, Abraham K. Gebre, Perry L. Colvin, Thomas L. Smith, Robert C. Murphy, Ilamadhab Mishra, John S. Parks

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

12/15 lipoxygenase (12/15LO) oxidizes polyunsaturated fatty acids (PUFAs) to form bioactive lipid mediators. The role of 12/15LO in atherosclerosis development remains controversial. We evaluated atherosclerosis development and lipid metabolism in 12/15LO-LDL receptor (LDLr) double knockout (DK) vs. LDLr knockout (SK) mice fed a PUFA-enriched diet to enhance production of 12/15LO products. Compared with SK controls, DK mice fed a PUFA-enriched diet had decreased plasma and liver lipid levels, hepatic lipogenic gene expression, VLDL secretion, and aortic atherosclerosis and increased VLDL turnover. Bone marrow transplantation and Kupffer cell ablation studies suggested both circulating leukocytes and Kupffer cells contributed to the lipid phenotype in 12/15LO-deficient mice. Conditioned medium from in vitro incubation of DK vs. SK macrophages reduced triglyceride secretion in McArdle 7777 hepatoma cells. Our results suggest that, in the context of dietary PUFA enrichment, macrophage 12/15LO expression adversely affects plasma and hepatic lipid metabolism, resulting in exacerbated atherosclerosis.

Original languageEnglish (US)
Pages (from-to)686-695
Number of pages10
JournalJournal of lipid research
Volume53
Issue number4
DOIs
StatePublished - Apr 2012

Keywords

  • Bone marrow transplantation
  • Hepatosteatosis
  • Kupffer cell
  • Vldl metabolism

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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