한빛사논문
- 조회486
Jibeom Lee1,7, Hyeonhui Kim2,7, Yun-Won Kang1, Yumin Kim1, Moon-young Park1, Ji-Hong Song1, Yunju Jo3, Tam Dao3, Dongryeol Ryu3, Junguee Lee4, Chang-Myung Oh1 and Sangkyu Park5,6
1Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, Korea.
2Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Korea.
3Department of Molecular Cell Biology, Sungkyunkwan University (SKKU) School of Medicine, Suwon, Korea.
4Department of Pathology, St Mary’s Hospital, the Catholic University of Korea, Daejeon, Korea.
5Department of Precision Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea.
6Mitohormesis Research Center, Yonsei University Wonju College of Medicine, Wonju, Gangwon-do, Korea.
7These authors contributed equally: Jibeom Lee, Hyeonhui Kim.
Corresponding authors : Correspondence to Chang-Myung Oh or Sangkyu Park.
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a serious metabolic disorder characterized by excess fat accumulation in the liver. Over the past decade, NAFLD prevalence and incidence have risen globally. There are currently no effective licensed drugs for its treatment. Thus, further study is required to identify new targets for NAFLD prevention and treatment. In this study, we fed C57BL6/J mice one of three diets, a standard chow diet, high-sucrose diet, or high-fat diet, and then characterized them. The mice fed a high-sucrose diet had more severely compacted macrovesicular and microvesicular lipid droplets than those in the other groups. Mouse liver transcriptome analysis identified lymphocyte antigen 6 family member D (Ly6d) as a key regulator of hepatic steatosis and the inflammatory response. Data from the Genotype-Tissue Expression project database showed that individuals with high liver Ly6d expression had more severe NAFLD histology than those with low liver Ly6d expression. In AML12 mouse hepatocytes, Ly6d overexpression increased lipid accumulation, while Ly6d knockdown decreased lipid accumulation. Inhibition of Ly6d ameliorated hepatic steatosis in a diet-induced NAFLD mouse model. Western blot analysis showed that Ly6d phosphorylated and activated ATP citrate lyase, which is a key enzyme in de novo lipogenesis. In addition, RNA- and ATAC-sequencing analyses revealed that Ly6d drives NAFLD progression by causing genetic and epigenetic changes. In conclusion, Ly6d is responsible for the regulation of lipid metabolism, and inhibiting Ly6d can prevent diet-induced steatosis in the liver. These findings highlight Ly6d as a novel therapeutic target for NAFLD.
논문정보
- Research article
- 2023년 07월 (BRIC 등록일 2023-07-03)
- 국내 연구진
- 의약학 > 분자세포의학
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