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Unsaturated fatty acids repress the expression of adipocyte fatty acid binding protein via the modulation of histone deacetylation in RAW 264.7 macrophages

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Abstract

Background

Adipocyte fatty acid binding protein (A-FABP) present in macrophages has been implicated in the integration of lipid metabolism and inflammatory response, contributing to development of insulin resistance and atherosclerosis.

Aim of the study

This study was conducted to test the hypothesis that the role of fatty acids in the inflammatory pathways is mediated through the modulation of A-FABP expression in macrophages.

Methods

Murine RAW 264.7 macrophages were treated with inflammatory insults and fatty acids for quantitative real-time PCR and Western blot analysis. The cells were treated with trichostatin A (TSA), a histone deacetylase inhibitor, for elucidating mechanisms for the regulation of A-FABP expression by fatty acids. RNA interference (RNAi) to knock down A-FABP was utilized to assess its role in inflammatory gene expression.

Results

When RAW 264.7 were incubated with lipopolysaccharides (LPS; 100 ng/ml) or 2.5 ng/ml of tumor necrosis factor α for 18 h, A-FABP mRNA and protein levels were drastically increased. Unsaturated fatty acids (100 μmol/l in complexed with BSA) such as palmitoleic acid, oleic acid, linoleic acid, linolenic acid, and eicosapentaenoic acid, significantly repressed the basal as well as LPS-induced A-FABP expression, whereas palmitic acid did not elicit the same effect. TSA increased A-FABP mRNA levels and abolished the repressive effect of linoleic acid on A-FABP expression in unstimulated and LPS-stimulated macrophages. Depletion of A-FABP expression by 70–80% using RNAi markedly decreased cyclooxygenase 2 mRNA abundance and potentiated the repression by linoleic acid.

Conclusion

Unsaturated fatty acids inhibited the basal as well as LPS-induced A-FABP expression. The mechanism may involve histone deacetylation and anti-inflammatory effect of unsaturated fatty acids may be at least in part attributed to their repression of A-FABP expression in RAW 264.7 macrophages.

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Abbreviations

A-FABP:

Adipocyte fatty acid binding protein

AP-1:

Activator protein 1

BSA:

Bovine serum albumin

COX-2:

Cyclooxygenase 2

CVD:

Cardiovascular disease

FBS:

Fetal bovine serum

HDACi:

Histone deacetylase inhibitor

IKK:

I kappa B kinase

IL-1β:

Interleukin-1β

LPS:

Lipopolysaccharides

MAPK:

Mitogen-activated protein kinases

MCP-1:

Monocyte chemoattractant protein 1

NF-κB:

Nuclear factor kappa B

PPARγ:

Peroxisome proliferator-activated receptor γ

qPCR:

Quantitative real-time PCR

siRNA:

Small interfering RNA

TNFα:

Tumor necrosis factor α

TSA:

Trichostatin A

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Acknowledgment

This work was supported by National Science Foundation-EPSCoR grant EPS-0346476.

Conflicts of interest

All authors read and approved the final manuscript and have no conflicts of interest.

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Author notes

  1. Ji-Young Lee

    Present address: Department of Nutritional Sciences, University of Connecticut, Storrs, CT, 06269, USA

Authors and Affiliations

  1. Department of Nutrition and Health Sciences, University of Nebraska, Lincoln, NE, 68583-0806, USA

    Ji-Young Lee

  2. Department of Nutrition and Health Sciences, University of Nebraska, Lincoln, NE, 68583, USA

    Sara L. Coleman & Young-Ki Park

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  1. Sara L. Coleman
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Coleman, S.L., Park, YK. & Lee, JY. Unsaturated fatty acids repress the expression of adipocyte fatty acid binding protein via the modulation of histone deacetylation in RAW 264.7 macrophages. Eur J Nutr 50, 323–330 (2011). https://doi.org/10.1007/s00394-010-0140-9

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  • DOI: https://doi.org/10.1007/s00394-010-0140-9

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