Comparative toxicity of oleic and linoleic acid on human lymphocytes

Cury-Boaventura, Maria Fernanda; Gorjão, Renata; Lima, Thaís Martins de; Newsholme, Philip; Curi, Rui

doi:10.1016/j.lfs.2005.07.038

Cited by 118 publications

(81 citation statements)

References 69 publications

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“…Different mechanisms are under discussion, which may lead to fatty acid lipotoxicity in different experimental systems. Programmed cell death (6, 38 -40), JNK-dependent TNF-related apoptosis (41), activation of peroxisome proliferator-activated receptor (42), and activation of the unfolded protein response (43)(44)(45)(46) with the ER may play a role in the observed lipotoxic effects (47,48). Finally, imbalance in cellular lipid metabolism leading to changes in membrane properties needs to be considered (5,6).…”

Section: Discussionmentioning

confidence: 99%

Oleate Inhibits Steryl Ester Synthesis and Causes Liposensitivity in Yeast

Connerth

Czabany

Wagner

et al. 2010

Journal of Biological Chemistry

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In the yeast Saccharomyces cerevisiae, neutral lipids can be synthesized by four acyltransferases, namely Dga1p and Lro1p producing triacylglycerols (TAG) and Are1p and Are2p forming steryl esters (SE). TAG and SE are stored in an organelle called lipid particles/droplet. Growth of yeast cells on oleate-supplemented media strongly induced proliferation of lipid particles and specifically the synthesis of TAG, which serve as the major pool for the excess of fatty acids. Surprisingly, SE synthesis was strongly inhibited under these conditions. Here, we show that this effect was not due to decreased expression of ARE2 encoding the major yeast SE synthase at the transcriptional level but to competitive enzymatic inhibition of Are2p by free oleate. Consequently, a triple mutant dga1⌬lro1⌬are1⌬ARE2 ؉ grown on oleate did not form substantial amounts of SE and exhibited a growth phenotype similar to the dga1⌬lro1⌬are1⌬are2⌬ quadruple mutant, including lack of lipid particles. Growth of these mutants on oleate was strongly delayed, and cell viability was decreased but rescued by adaptation. In these strains, oleate stress caused morphological changes of intracellular membranes, altered phospholipid composition and formation of an additional lipid class, ethyl esters of fatty acids. In summary, our data showed that exposure to oleate led to disturbed lipid and membrane homeostasis along with liposensitivity of the yeast.

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Section: Discussionmentioning

confidence: 99%

Oleate Inhibits Steryl Ester Synthesis and Causes Liposensitivity in Yeast

Connerth

Czabany

Wagner

et al. 2010

Journal of Biological Chemistry

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“…The inhibitory effect of FA on NO production may be due to their cytotoxicity, as observed by loss of membrane integrity and/or increase of DNA fragmentation in cells treated for 48 h with high concentrations. FA toxicity has been reported in several cell types, as a concentration and time-dependent effect of these metabolites [35,36].…”

Section: Discussionmentioning

confidence: 99%

Fatty acid control of nitric oxide production by macrophages

Lima

Scavone

et al. 2006

FEBS Letters

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Modulation of macrophage functions by fatty acids (FA) has been studied by several groups, but the effect of FA on nitric oxide production by macrophages has been poorly examined. In the present study the effect of palmitic, stearic, oleic, linoleic, arachidonic, docosahexaenoic and eicosapentaenoic acids on NF-jB activity and NO production in J774 cells (a murine macrophage cell line) was investigated. All FA tested stimulated NO production at low doses (1-10 lM) and inhibited it at high doses (50-200 lM). An increase of iNOS expression and activity in J774 cells treated with a low concentration of FA (5 lM) was observed. The activity of NF-jB was time-dependently enhanced by the FA treatment. The inhibitory effect of FA on NO production may be due to their cytotoxicity, as observed by loss of membrane integrity and/or increase of DNA fragmentation in cells treated for 48 h with high concentrations. The results indicate that, at low concentrations FA increase NO production by J774 cells, whereas at high concentrations they cause cell death.

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“…Known lipid-cell interactions suggest that saturated fatty acids may be more toxic to cells than unsaturated fatty acids. 9,19,20 A natural response of monocytes exposed to exogenous molecules is cell activation. [8][9][10][11] Here the result is the generation of intracellular lipid droplets, which may incorporate both endogenous and exogenous lipids.…”

Section: Journal Of Biomedical Opticsmentioning

confidence: 99%

“…9,19,20 A natural response of monocytes exposed to exogenous molecules is cell activation. [8][9][10][11] Here the result is the generation of intracellular lipid droplets, which may incorporate both endogenous and exogenous lipids. In particular, unsaturated lipids, such as oleic acid, are thought to enter cells by penetrating the plasma membrane through a flip-flop mechanism, which might explain the apparent high accumulation of deuterated oleic acid near the plasma membrane.…”

Section: Journal Of Biomedical Opticsmentioning

confidence: 99%

“…[5][6][7] More recently, monocytes have also been observed to develop lipid droplets in response to direct exposure to a combination of triglyceride-rich lipoprotein (TGRL) lipolysis products consisting of lipoprotein remnant particles, diglycerides, monoglycerides, phospholipids, and free fatty acids. [8][9][10][11] Production of TGRL lipolysis products in high physiological to pathophysiological concentrations of TGRL lipolysis products has been linked to vascular inflammation and atherosclerosis. 6,8,10,11 Obtaining a better understanding of the biogenesis of lipid droplets and the steps leading to related cellular lipid accumulations in vitro and in vivo will ultimately allow us to devise therapies for the avoidance and/or treatment of many lipid-related disorders and diseases.…”

Section: Introductionmentioning

confidence: 99%

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Lipid-cell interactions in human monocytes investigated by doubly-resonant coherent anti-Stokes Raman scattering microscopy

et al. 2011

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Abstract. We demonstrate that doubly-resonant coherent anti-Stokes Raman scattering can provide enhanced and highly specific contrast for molecules containing unique Raman-active small molecular groups. This combination provides contrast for molecules that can otherwise be difficult to discriminate by Raman spectroscopy. Here, human monocytes were incubated with either deuterated oleic acid or 17-octadecynoic acid (a fatty acid with an end terminal acetylene group). The carbon-deuterium stretching vibration of the deuterated fatty acid, as well as the unique alkyne stretching vibration of the alkyne-containing fatty acid, were used to provide contrast for these exogenous free fatty acids. The combination of these unique modes with the common aliphatic carbon-hydrogen stretching vibration inherent to all fatty acid allowed for doubly-resonant detection of these unique molecules and enabled us to detect the presence of these lipids in areas within a cell where each molecular resonance by itself did not generate sufficient signal. C 2011 Society of Photo-Optical Instrumentation Engineers (SPIE).

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Comparative toxicity of oleic and linoleic acid on human lymphocytes

Cited by 118 publications

References 69 publications

Oleate Inhibits Steryl Ester Synthesis and Causes Liposensitivity in Yeast

Oleate Inhibits Steryl Ester Synthesis and Causes Liposensitivity in Yeast

Fatty acid control of nitric oxide production by macrophages

Lipid-cell interactions in human monocytes investigated by doubly-resonant coherent anti-Stokes Raman scattering microscopy

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