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Ablation of the deubiquitinase USP15 ameliorates nonalcoholic fatty liver disease and nonalcoholic steatohepatitis

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Author(s)
Jung-Hwan BaekMyung Sup KimHye Ryeon JungMin-Seon HwangChan-Ho LeeDai Hoon HanYong-Ho LeeEugene C YiSeung-Soon ImIlseon HwangKyungeun KimJoon-Yong ChungKyung-Hee Chun
Keimyung Author(s)
Im, Seung SoonHwang, Il Seon
Department
Dept. of Physiology (생리학)
Dept. of Pathology (병리학)
Journal Title
Exp Mol Med
Issued Date
2023
Volume
55
Issue
7
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.
Keimyung Author(s)(Kor)
임승순
황일선
Publisher
School of Medicine (의과대학)
Type
Article
ISSN
2092-6413
Source
https://www.nature.com/articles/s12276-023-01036-7
DOI
10.1038/s12276-023-01036-7
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/45035
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Pathology (병리학)
1. School of Medicine (의과대학) > Dept. of Physiology (생리학)
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