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.
Keywords
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Article info
Publication history
Published online: July 26, 2006
Accepted:
June 6,
2006
Received in revised form:
May 26,
2006
Received:
August 4,
2005
Identification
Copyright
© 2006 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
