{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T22:20:20Z","timestamp":1793830820055,"version":"4.6.1"},"reference-count":41,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,4,3]],"date-time":"2021-04-03T00:00:00Z","timestamp":1617408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 109-2311-B-010-003, MOST 109-2634-F-010-001, MOST 109-2327-B-010-002, MOST 107-2320-B-010-037-MY3"],"award-info":[{"award-number":["MOST 109-2311-B-010-003, MOST 109-2634-F-010-001, MOST 109-2327-B-010-002, MOST 107-2320-B-010-037-MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Nonalcoholic fatty liver disease (NAFLD) and its more severe form, nonalcoholic steatohepatitis (NASH), are the most common chronic liver diseases worldwide. However, drugs to treat NAFLD and NASH are an unmet clinical need. This study sought to provide evidence that Cisd2 is a molecular target for the development of treatments targeting NAFLD and NASH. Several discoveries are pinpointed. The first is that Cisd2 dosage modulates the severity of Western diet-induced (WD-induced) NAFLD. Specifically, Cisd2 haploinsufficiency accelerates NAFLD development and exacerbates progression toward NASH. Conversely, an enhanced Cisd2 copy number attenuates liver pathogenesis. Secondly, when a WD is fed to mice, transcriptomic analysis reveals that the major alterations affecting biological processes are related to inflammation, lipid metabolism, and DNA replication\/repair. Thirdly, among these differentially expressed genes, the most significant changes involve Nrf2-mediated oxidative stress, cholesterol biosynthesis, and fatty acid metabolism. Finally, increased Cisd2 expression protects the liver from oxidative stress and reduces the occurrence of mitochondrial DNA deletions. Taken together, our mouse model reveals that Cisd2 plays a crucial role in protecting the liver from WD-induced damages. The development of therapeutic agents that effectively enhance Cisd2 expression is one potential approach to the treatment of WD-induced fatty liver diseases.<\/jats:p>","DOI":"10.3390\/antiox10040559","type":"journal-article","created":{"date-parts":[[2021,4,3]],"date-time":"2021-04-03T22:03:36Z","timestamp":1617487416000},"page":"559","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Cisd2 Protects the Liver from Oxidative Stress and Ameliorates Western Diet-Induced Nonalcoholic Fatty Liver Disease"],"prefix":"10.3390","volume":"10","author":[{"given":"Yi-Long","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung University, Taipei 112, Taiwan"},{"name":"Aging and Health Research Center, National Yang Ming Chiao Tung University, Taipei 112, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9126-0219","authenticated-orcid":false,"given":"Zhao-Qing","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung University, Taipei 112, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen-Hua","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung University, Taipei 112, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan-Chi","family":"Teng","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung University, Taipei 112, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao-Hsiung","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung University, Taipei 112, Taiwan"},{"name":"Aging and Health Research Center, National Yang Ming Chiao Tung University, Taipei 112, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting-Fen","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung University, Taipei 112, Taiwan"},{"name":"Aging and Health Research Center, National Yang Ming Chiao Tung University, Taipei 112, Taiwan"},{"name":"Institute of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan 350, Taiwan"},{"name":"Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Zhunan 350, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1053\/j.gastro.2020.01.052","article-title":"Nonalcoholic fatty liver disease 2020: The state of the disease","volume":"158","author":"Cotter","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/s41575-019-0145-7","article-title":"From NASH to HCC: Current concepts and future challenges","volume":"16","author":"Anstee","year":"2019","journal-title":"Nat. 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