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Tannic acid, a novel histone acetyltransferase inhibitor, prevents non-alcoholic fatty liver disease both in vivo and in vitro model

Authors
 Min-Yu Chung  ;  Ji-Hye Song  ;  Jinhyuk Lee  ;  Eun Ju Shin  ;  Jae Ho Park  ;  Seung-Hyun Lee  ;  Jin-Taek Hwang  ;  Hyo-Kyoung Choi 
Citation
 MOLECULAR METABOLISM, Vol.19 : 34-48, 2019 
Journal Title
 MOLECULAR METABOLISM 
Issue Date
2019
Abstract
OBJECTIVE: We examined the potential of tannic acid (TA) as a novel histone acetyltransferase inhibitor (HATi) and demonstrated that TA prevents non-alcoholic fatty liver disease (NAFLD) by inhibiting HAT activity. METHODS: The anti-HAT activity of TA was examined using HAT activity assays. An in vitro NAFLD model was generated by treating HepG2 cells with oleic and palmitic acids. Male C57BL/6J mice were fed a control diet (CD) or Western diet (WD) with or without supplementation with either 1% or 3% TA (w/w) for 12 weeks. Finally, the possibility of interacting p300 and TA was simulated. RESULTS: TA suppressed HAT activity both in vitro and in vivo. Interestingly, TA abrogated occupancy of p300 on the sterol regulatory element in the fatty acid synthase and ATP-citrate lyase promoters, eventually inducing hypoacetylation of H3K9 and H3K36. Furthermore, TA decreased acetylation at lysine residues 9 and 36 of histone H3 protein and that of total proteins. Consequently, TA decreased the mRNA expression of lipogenesis-related genes and attenuated lipid accumulation in vivo. We observed that NAFLD features, including body weight, liver mass, fat mass, and lipid profile in serum, were improved by TA supplementation in vivo. Finally, we demonstrated the possibility that TA directly binds to p300 through docking simulation between ligand and protein. CONCLUSIONS: Our findings demonstrate that TA, a novel HATi, has potential application for the prevention of NAFLD.
Files in This Item:
T201901541.pdf Download
DOI
10.1016/j.molmet.2018.11.001
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Lee, Seung Hyun(이승현) ORCID logo https://orcid.org/0000-0001-7549-9430
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/169933
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