Free fatty acid-induced histone acetyltransferase activity accelerates lipid accumulation in HepG2 cells
10.4162/nrp.2019.13.3.196
- Author:
Sangwon CHUNG
1
;
Jin Taek HWANG
;
Jae Ho PARK
;
Hyo Kyoung CHOI
Author Information
1. Korea Food Research Institute, 245, Nongsaengmyeong-ro, Iseo-myeon, Wanju-gun, Jeonbuk 55365, Republic of Korea. chkyoung@kfri.re.kr
- Publication Type:Original Article
- Keywords:
Histone acetyltransferases;
lipogenesis;
non-alcoholic fatty liver disease;
lipid metabolism;
HepG2 cell
- MeSH:
Acetylation;
Dietary Supplements;
Epigenomics;
Hep G2 Cells;
Histone Acetyltransferases;
Histones;
Lipid Metabolism;
Lipogenesis;
Liver;
Lysine;
Metabolic Diseases;
Non-alcoholic Fatty Liver Disease;
RNA, Messenger;
Sterol Regulatory Element Binding Protein 1
- From:Nutrition Research and Practice
2019;13(3):196-204
- CountryRepublic of Korea
- Language:English
-
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 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.
