Date Published: June 6, 2019
Publisher: Public Library of Science
Author(s): Moonju Hong, Jin-Taek Hwang, Eun Ju Shin, Haeng Jeon Hur, Keunsoo Kang, Hyo-Kyoung Choi, Min-Yu Chung, Sangwon Chung, Mi Jeong Sung, Jae-Ho Park, Miguel Branco.
Hepatic steatosis is the most common chronic liver disease in Western countries. Both genetic and environmental factors are known as causes of the disease although their underlying mechanisms have not been fully understood. This study investigated the association of DNA methylation with oleic acid-induced hepatic steatosis. It also examined effects of food components on DNA methylation in hepatic steatosis. Genome-wide DNA methylation of oleic acid (OA)-induced lipid accumulation in vitro cell model was investigated using reduced representation bisulfite sequencing. Changes of DNA methylation were also analyzed after treatment with food components decreasing OA-induced lipid accumulation in the model. We identified total 81 regions that were hypermethylated by OA but hypomethylated by food components or vice versa. We determined the expression of seven genes proximally located at the selected differentially methylated regions. Expression levels of WDR27, GNAS, DOK7, MCF2L, PRKG1, and CMYA5 were significantly different between control vs OA and OA vs treatment with food components. We demonstrated that DNA methylation was associated with expression of genes in the model of hepatic steatosis. We also found that food components reversely changed DNA methylation induced by OA and alleviated lipid accumulation. These results suggest that DNA methylation is one of the mechanisms causing the hepatic steatosis and its regulation by food components provides insights that may prevent or alleviate lipid accumulation.
Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease caused by fat accumulation in the liver due to imbalance between triglyceride (TG) acquisition and removal without alcohol consumption . Progress of NAFLD ranges from simple hepatic steatosis to non-alcoholic steatohepatitis (NASH), fibrosis, and even hepatic cancer. NAFLD is associated with obesity, dyslipidemia, and insulin resistance, which are also known as characteristics of metabolic syndromes . Although the pathogenesis of NAFLD is not fully understood, it has been shown that hepatic de novo lipogenesis is increased by activation of lipogenic factors such as SREBP-1c, PPARγ, and fatty acid synthase (FASN) [2–5]. Subsequently, accumulation of free fatty acids (FFAs) in the liver causes lipotoxicity and oxidative stress, which lead to hepatocyte injury and progress to NASH and fibrosis [2–4]. It is of interest that dietary factors affect de novo hepatic lipogenesis via the crucial factors FASN and PPARγ, and can thereby mitigate NAFLD and obesity, based on a cell and an animal model [6, 7]. However, underlying mechanisms of the regulation have not been clearly elucidated.