Regulation of histone deacetylases by fatty acids in RAW 264.7 macrophages

Histone deacetylases (HDACs) play a critical role in gene expression through their ability to regulate chromatin structure by promoting tight association of histones and DNA. Therefore, factors that alter HDAC activity could have a large impact on gene transcription. We investigated whether fatty acids (FA) commonly present in diet can modulate mRNA, protein and activity of HDACs in RAW 264.7 macrophages. Quantitative realtime PCR analysis demonstrated that HDAC1 showed the highest mRNA expression followed by HDAC5, 2, 3 and 4 among 11 isoforms investigated. When RAW 264.7 macrophages were treated with 100 μM of FA complexed with BSA (BSA to FA molar ratio of 2.5) for 24 hr, palmitate significantly reduced HDAC activity compared with control and linoleate. In a time course study, cells were incubated with 100 μM of palmitate, oleate, linoleate, eicosapentaenoic acid and docosahexaenoic acid for 6, 12, and 24 hr. After 12 hr, linoleate significantly increased HDAC1, 3, and 5 mRNA levels whereas a significant reduction in HDAC2, 3, 5, and 9 mRNA abundance was observed with palmitate compared with the control after 24 hr. However, the mRNA levels did not mirror protein levels as HDAC 3 and 4 proteins were lowered by palmitate at 12 hr incubation. In conclusion, our results indicate that common FA in diet can modulate HDAC activity at the transcriptional as well as the post‐transcriptional levels in RAW 264.7 macrophages.