Document Detail

Unsaturated fatty acids repress the expression of adipocyte fatty acid binding protein via the modulation of histone deacetylation in RAW 264.7 macrophages.
MedLine Citation:
PMID:  21046125     Owner:  NLM     Status:  In-Data-Review    
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.
Sara L Coleman; Young-Ki Park; Ji-Young Lee
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Publication Detail:
Type:  Journal Article     Date:  2010-11-03
Journal Detail:
Title:  European journal of nutrition     Volume:  50     ISSN:  1436-6215     ISO Abbreviation:  Eur J Nutr     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-08-08     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100888704     Medline TA:  Eur J Nutr     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  323-30     Citation Subset:  IM    
Department of Nutrition and Health Sciences, University of Nebraska, Lincoln, NE, 68583, USA.
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