Palmitate promotes monocyte atherogenicity via de novo ceramide synthesis

Dan Gao, Chathyan Pararasa, Christopher R Dunston, Clifford J. Bailey, Helen R. Griffiths

Research output: Contribution to journalArticle

Abstract

Elevated plasma free fatty acids (FAs) are associated with increased risk of cardiovascular disease. This study investigates the effects of the saturated FA palmitate and unsaturated FA oleate on monocyte phenotype and function. Incubation of human U937 and THP-1 monocytes with palmitate for 24h increased cell surface expression of integrin CD11b and scavenger receptor CD36 in a concentration-dependent manner with some decrease in mitochondrial reducing capacity at high concentration (300µM). Monocytes incubated with palmitate, but not oleate, showed increased uptake of oxidized LDL and increased adhesion to rat aortic endothelium, particularly at bifurcations. The palmitate-induced increase in CD11b and CD36 expression was associated with increased cellular C16 ceramide and sphingomyelin, loss of reduced glutathione, and increased reactive oxygen species (ROS). Increased monocyte surface CD11b and CD36 was inhibited by fumonisin B1, an inhibitor of de novo ceramide synthesis, but not by the superoxide dismutase mimetic MnTBap. In contrast, MnTBap prevented the mitochondrial ROS increase and metabolic inhibition due to 300µM palmitate. This study demonstrates that in viable monocytes, palmitate but not oleate increases expression of surface CD11b and CD36. Palmitate increases monocyte adhesion to the aortic wall and promotes uptake of oxidized LDL and this involves de novo ceramide synthesis.
Original languageEnglish
Pages (from-to)796–806
Number of pages11
JournalFree Radical Biology and Medicine
Volume53
Issue number4
Early online date26 May 2012
DOIs
Publication statusPublished - 15 Aug 2012

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Palmitates
Ceramides
Monocytes
Oleic Acid
Reactive Oxygen Species
Adhesion
Scavenger Receptors
Sphingomyelins
Unsaturated Fatty Acids
Nonesterified Fatty Acids
Integrins
Superoxide Dismutase
Endothelium
Glutathione
Rats
Cardiovascular Diseases
Fatty Acids
Phenotype
Plasmas

Cite this

Gao, Dan ; Pararasa, Chathyan ; Dunston, Christopher R ; Bailey, Clifford J. ; Griffiths, Helen R. / Palmitate promotes monocyte atherogenicity via de novo ceramide synthesis. In: Free Radical Biology and Medicine. 2012 ; Vol. 53, No. 4. pp. 796–806.
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Palmitate promotes monocyte atherogenicity via de novo ceramide synthesis. / Gao, Dan; Pararasa, Chathyan; Dunston, Christopher R; Bailey, Clifford J.; Griffiths, Helen R.

In: Free Radical Biology and Medicine, Vol. 53, No. 4, 15.08.2012, p. 796–806.

Research output: Contribution to journalArticle

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