Research Group of Healthcare, Korea Food Research Institute, Wanju-gun, Jeollabuk-do, Korea.
Department of Food Biotechnology, Korea University of Science and Technology, Daejeon, Korea.
J Med Food. 2021 Sep;24(9):978-986. doi: 10.1089/jmf.2021.K.0048.
Epigenetic regulation by histone acetyltransferase (HAT) is associated with various biological processes and the progression of diseases, including nonalcoholic fatty liver disease (NAFLD). The objective of this study was to investigate whether the hypolipidemic properties of black mulberry ( Roxb.) fruit extract (BME) contribute toward protection against NAFLD by HAT inhibition. HepG2 cells were treated with oleic and palmitic acids to induce lipid accumulation, which was significantly attenuated by the treatment with BME at 50 and 100 g/mL. BME also markedly reduced the expression of proteins associated with lipogenesis, which was attributed to the BME-mediated downregulation of lipogenic genes in HepG2 cells. BME significantly inhibited total HAT and p300 activities. In addition, BME suppressed total acetylated lysine as well as specific histone acetylation of proteins H3K14 and H3K27 in HepG2 cells. Mice were then fed with either a chow diet or western diet (WD), with or without BME (1%, ) supplementation, for 12 weeks to confirm hypolipidemic activity of BME. BME attenuated serum nonesterified fatty acids and low-density lipoprotein (LDL) cholesterol levels, which was likely associated with the downregulation of hepatic lipogenic gene expression in WD-fed obese mice. Taken together, the hypolipidemic activity of BME was observed in HepG2 cells treated with fatty acids as well as in livers of obese mice, and the hepatoprotection of BME is likely associated with the inhibition of acetylation. Further investigation is warranted to determine whether BME can be developed into an efficacious dietary intervention to attenuate the progression of NAFLD by epigenetic regulation in clinical settings.
组蛋白乙酰转移酶 (HAT) 的表观遗传调控与多种生物学过程和疾病的进展有关，包括非酒精性脂肪性肝病 (NAFLD)。本研究旨在探讨黑桑椹（Roxb.）果提取物（BME）的降血脂特性是否通过抑制 HAT 对 NAFLD 起到保护作用。用油酸和棕榈酸处理 HepG2 细胞以诱导脂质积累，用 50 和 100μg/ml 的 BME 处理可显著减弱这种作用。BME 还明显降低了与脂肪生成相关的蛋白表达，这归因于 BME 介导的 HepG2 细胞中脂肪生成基因的下调。BME 显著抑制了总 HAT 和 p300 的活性。此外，BME 抑制了 HepG2 细胞中总乙酰化赖氨酸以及特定组蛋白 H3K14 和 H3K27 的乙酰化。然后，用标准饮食或西方饮食（WD）喂养小鼠，并用或不用 BME（1%，）补充 12 周，以确认 BME 的降血脂活性。BME 降低了血清非酯化脂肪酸和低密度脂蛋白（LDL）胆固醇水平，这可能与 WD 喂养肥胖小鼠肝脏中脂肪生成基因表达的下调有关。总之，BME 在脂肪酸处理的 HepG2 细胞以及肥胖小鼠的肝脏中表现出降血脂活性，BME 的肝保护作用可能与抑制乙酰化有关。需要进一步的研究来确定 BME 是否可以开发成一种有效的饮食干预措施，通过表观遗传调控在临床环境中减轻 NAFLD 的进展。
