한빛사논문
- 조회580
Jung-Hwan Baek1,9, Myung Sup Kim1,9, Hye Ryeon Jung2, Min-Seon Hwang1, Chan-ho Lee1, Dai Hoon Han3, Yong-ho Lee 4, Eugene C. Yi2, Seung-Soon Im5, Ilseon Hwang6, Kyungeun Kim7, Joon-Yong Chung8 and Kyung-Hee Chun1
1Department of Biochemistry & Molecular Biology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, South Korea.
2Department of Molecular Medicine and Biopharmaceutical Sciences, School of Convergence Science and Technology and College of Medicine or College of Pharmacy, Seoul National University, Seoul 03080, South Korea.
3Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea.
4Department of Internal Medicine, Yonsei University College of Medicine, Seodaemun-gu, Seoul 03722, South Korea.
5Department of Physiology, Keimyung University School of Medicine, Daegu 42601, South Korea.
6Department of Pathology, Keimyung University School of Medicine, Daegu, South Korea.
7Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 03181, South Korea.
8Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
9These authors contributed equally: Jung-Hwan Baek, Myung Sup Kim.
These authors contributed equally: Jung-Hwan Baek, Myung Sup Kim.
Corresponding author : Correspondence to Kyung-Hee Chun.
Abstract
Nonalcoholic fatty liver disease (NAFLD) occurs due to the accumulation of fat in the liver, leading to fatal liver diseases such as nonalcoholic steatohepatitis (NASH) and cirrhosis. Elucidation of the molecular mechanisms underlying NAFLD is critical for its prevention and therapy. Here, we observed that deubiquitinase USP15 expression was upregulated in the livers of mice fed a high-fat diet (HFD) and liver biopsies of patients with NAFLD or NASH. USP15 interacts with lipid-accumulating proteins such as FABPs and perilipins to reduce ubiquitination and increase their protein stability. Furthermore, the severity of NAFLD induced by an HFD and NASH induced by a fructose/palmitate/cholesterol/trans-fat (FPC) diet was significantly ameliorated in hepatocyte-specific USP15 knockout mice. Thus, our findings reveal an unrecognized function of USP15 in the lipid accumulation of livers, which exacerbates NAFLD to NASH by overriding nutrients and inducing inflammation. Therefore, targeting USP15 can be used in the prevention and treatment of NAFLD and NASH.
논문정보
- Research article
- 2023년 07월 (BRIC 등록일 2023-07-21)
- 국내(교신)+국외 연구진
- 의약학 > 분자세포의학
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