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KMID : 1239920190130030196
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Nutrition Research and Practice
2019 Volume.13 No. 3 p.196 ~ p.204
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Free fatty acid-induced histone acetyltransferase activity accelerates lipid accumulation in HepG2 cells
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Chung Sang-Won
Hwang Jin-Taek
Park Jae-Ho
Choi Hyo-Kyoung
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Abstract
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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 PPARγ, 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.
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KEYWORD
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Histone acetyltransferases, lipogenesis, non-alcoholic fatty liver disease, lipid metabolism, HepG2 cell
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