Nutr Res Pract.  2019 Jun;13(3):196-204. 10.4162/nrp.2019.13.3.196.

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

Affiliations
  • 1Korea Food Research Institute, 245, Nongsaengmyeong-ro, Iseo-myeon, Wanju-gun, Jeonbuk 55365, Republic of Korea. chkyoung@kfri.re.kr
  • 2Department of Food Biotechnology, Korea University of Science & Technology, Daejeon 34113, Republic of Korea.

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.

Keyword

Histone acetyltransferases; lipogenesis; non-alcoholic fatty liver disease; lipid metabolism; HepG2 cell

MeSH Terms

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
Histone Acetyltransferases
Histones
Lysine
RNA, Messenger
Sterol Regulatory Element Binding Protein 1
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