Sustained elevations in NEFA induce cyclooxygenase-2 activity and potentiate THP-1 macrophage foam cell formation

Eric E. Lloyd, John W. Gaubatz, Alan R. Burns, Henry J. Pownall

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Type 2 diabetes, a major risk factor for atherosclerosis, is associated with a cluster of lipid risk factors, many of which can be mechanistically linked with underlying dysregulated fatty acid metabolism and elevated plasma non-esterified fatty acids (NEFA). Thus, we tested the hypothesis that elevated NEFA dysregulates lipid metabolism at the levels of lipid synthesis and gene expression in THP-1 monocyte derived macrophages (MDM). THP-1 MDM incubated with oleic acid (OA) and a BODIPY-conjugated NEFA, accumulate, respectively, intracellular inclusions that are positive for oil red O and BODIPY-labeling. Parallel studies with [14C]OA show dose-dependent accumulation of intracellular 14C-labeled neutral lipid, almost exclusively as triglyceride; the rate of [3H]OA uptake increases as THP-1 MDM convert to foam cells. Preincubation of THP-1 MDM with higher concentrations of OA (1.8 mM versus 0.2 mM) was associated with enhanced uptake of Ac-LDL, and increased expression of adipocyte fatty acid binding protein, FAT/CD36, and cyclooxygenase-2 (COX-2); COX-2 mass and activity also increased. These observations suggest a mechanistic link between sustained elevations in albumin-bound NEFA and foam cell formation that may be mediated by enhanced adipogenesis, increased uptake of modified LDL, and upregulated formation of eicosanoids, which may be proinflammatory.

Original languageEnglish (US)
Pages (from-to)49-55
Number of pages7
JournalAtherosclerosis
Volume192
Issue number1
DOIs
StatePublished - May 2007

Keywords

  • Adipogenesis
  • Atherosclerosis
  • COX-2
  • Inflammation
  • NEFA

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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