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

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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.

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.

참고문헌 (40)

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관련 논문AI추천

Physiologic and epigenetic effects of nutrients on disease pathways정민유, Hwang Jin-Taek, Lee Jaein, Park Soo-Hyun한국영양학회 · Nutrition Research and Practice2023 · 제17권 제1호비알코올성 지방간 세포 모델에서 곤포의 효능과 기전 연구이인, 권민정, 권정남, 김소연, 박성하, 주명수, 최준용, 한창우, 홍진우대한한방내과학회 · 대한한방내과학회지2014 · 제35권 제2호Fermented Soymilk Alleviates Lipid Accumulation by Inhibition of SREBP-1 and Activation of NRF-2 in the Hepatocellular Steatosis Model김리지, 김지현, 안상봉, 이종훈, 이태복, 전대원, 전진현, Wen Hao Wu한국미생물·생명공학회 · Journal of Microbiology and Biotechnology2018 · 제28권 제2호중만분소환 추출물이 Palmitate로 유발된 비알코올성 지방간 HepG2 cell 모델에 미치는 영향이지원, 전상윤, 최창원, 하예진, 한창우대한한방내과학회 · 대한한방내과학회지2016 · 제37권 제3호Ethanol extract of Allium fistulosum inhibits development of non-alcoholic fatty liver disease박재호, 신은주, 정민유, 정상원, 최효경, 황진택한국영양학회 · Nutrition Research and Practice2018 · 제12권 제2호곽향과 금전초 추출물이 Palmitic acid로 유발된 비알코올성 지방간 세포 모델에 미치는 영향김영광, 김은지, 문영호, 이다은, 이혜인, 임현찬대한한방내과학회 · 대한한방내과학회지2018 · 제39권 제3호

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