Browsing by Author "Kim, Seung-Jin"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Ethanol and its Nonoxidative Metabolites Promote Acute Liver Injury by Inducing ER Stress, Adipocyte Death, and Lipolysis
    (Elsevier, 2023) Park, Seol Hee; Seo, Wonhyo; Xu, Ming-Jiang; Mackowiak, Bryan; Lin, Yuhong; He, Yong; Fu, Yaojie; Hwang, Seonghwan; Kim, Seung-Jin; Guan, Yukun; Feng, Dechun; Yu, Liqing; Lehner, Richard; Liangpunsakul, Suthat; Gao, Bin; Medicine, School of Medicine
    Background & aims: Binge drinking in patients with metabolic syndrome accelerates the development of alcohol-associated liver disease. However, the underlying mechanisms remain elusive. We investigated if oxidative and nonoxidative alcohol metabolism pathways, diet-induced obesity, and adipose tissues influenced the development of acute liver injury in a single ethanol binge model. Methods: A single ethanol binge was administered to chow-fed or high-fat diet (HFD)-fed wild-type and genetically modified mice. Results: Oral administration of a single dose of ethanol induced acute liver injury and hepatic endoplasmic reticulum (ER) stress in chow- or HFD-fed mice. Disruption of the Adh1 gene increased blood ethanol concentration and exacerbated acute ethanol-induced ER stress and liver injury in both chow-fed and HFD-fed mice, while disruption of the Aldh2 gene did not affect such hepatic injury despite high blood acetaldehyde levels. Mechanistic studies showed that alcohol, not acetaldehyde, promoted hepatic ER stress, fatty acid synthesis, and increased adipocyte death and lipolysis, contributing to acute liver injury. Increased serum fatty acid ethyl esters (FAEEs), which are formed by an enzyme-mediated esterification of ethanol with fatty acids, were detected in mice after ethanol gavage, with higher levels in Adh1 knockout mice than in wild-type mice. Deletion of the Ces1d gene in mice markedly reduced the acute ethanol-induced increase of blood FAEE levels with a slight but significant reduction of serum aminotransferase levels. Conclusions: Ethanol and its nonoxidative metabolites, FAEEs, not acetaldehyde, promoted acute alcohol-induced liver injury by inducing ER stress, adipocyte death, and lipolysis.
  • Thumbnail Image
    Item
    The Role of Epigenetic Changes in the Progression of Alcoholic Steatohepatitis
    (Frontiers Media, 2021-07-16) Kim, Hyeong Geug; Cho, Jung-Hyo; Kim, Jeongkyu; Kim, Seung-Jin; Biochemistry and Molecular Biology, School of Medicine
    Alcoholic steatohepatitis (ASH) is a progression hepatitis with severe fatty liver and its mortality rate for 30-days in patients are over 30%. Additionally, ASH is well known for one-fifth all alcoholic related liver diseases in the world. Excessive chronic alcohol consumption is one of the most common causes of the progression of ASH and is associated with poor prognosis and liver failure. Alcohol abuse dysregulates the lipid homeostasis and causes oxidative stress and inflammation in the liver. Consequently, metabolic pathways stimulating hepatic accumulation of excessive lipid droplets are induced. Recently, many studies have indicated a link between ASH and epigenetic changes, showing differential expression of alcohol-induced epigenetic genes in the liver. However, the specific mechanisms underlying the pathogenesis of ASH remain elusive. Thus, we here summarize the current knowledge about the roles of epigenetics in lipogenesis, inflammation, and apoptosis in the context of ASH pathophysiology. Especially, we highlight the latest findings on the roles of Sirtuins, a conserved family of class-III histone deacetylases, in ASH. Additionally, we discuss the involvement of DNA methylation, histone modifications, and miRNAs in ASH as well as the ongoing efforts for the clinical translation of the findings in ASH-related epigenetic changes.