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http://dx.doi.org/10.4162/nrp.2019.13.3.196

Free fatty acid-induced histone acetyltransferase activity accelerates lipid accumulation in HepG2 cells  

Chung, Sangwon (Korea Food Research Institute)
Hwang, Jin-Taek (Korea Food Research Institute)
Park, Jae Ho (Korea Food Research Institute)
Choi, Hyo-Kyoung (Korea Food Research Institute)
Publication Information
Nutrition Research and Practice / v.13, no.3, 2019 , pp. 196-204 More about this Journal
Abstract
BACKGROUND/OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disease triggered by epigenetic alterations, including lysine acetylation at histone or non-histone proteins, affecting the stability or transcription of lipogenic genes. Although various natural dietary compounds have anti-lipogenic effects, their effects on the acetylation status and lipid metabolism in the liver have not been thoroughly investigated. MATERIALS/METHODS: Following oleic-palmitic acid (OPA)-induced lipid accumulation in HepG2 cells, the acetylation status of histone and non-histone proteins, HAT activity, and mRNA expression of representative lipogenic genes, including $PPAR{\gamma}$, SREBP-1c, ACLY, and FASN, were evaluated. Furthermore, correlations between lipid accumulation and HAT activity for 22 representative natural food extracts (NExs) were evaluated. RESULTS: Non-histone protein acetylation increased following OPA treatment and the acetylation of histones H3K9, H4K8, and H4K16 was accelerated, accompanied by an increase in HAT activity. OPA-induced increases in the mRNA expression of lipogenic genes were down-regulated by C-646, a p300/CBP-specific inhibitor. Finally, we detected a positive correlation between HAT activity and lipid accumulation (Pearson's correlation coefficient = 0.604) using 22 NExs. CONCLUSIONS: Our results suggest that NExs have novel applications as nutraceutical agents with HAT inhibitor activity for the prevention and treatment of NAFLD.
Keywords
Histone acetyltransferases; lipogenesis; non-alcoholic fatty liver disease; lipid metabolism; HepG2 cell;
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