{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T08:59:43Z","timestamp":1790067583490,"version":"4.0.1"},"reference-count":52,"publisher":"SAGE Publications","issue":"7-9","license":[{"start":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T00:00:00Z","timestamp":1685664000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:sec>\n                    <jats:title>Aims:<\/jats:title>\n                    <jats:p>\n                      Studies demonstrated that oxidized fish oil (OFO) promoted oxidative stress and induced mitochondrial dysfunction and lipotoxicity, which attenuated beneficial effects of fish oil supplements in the treatment of nonalcoholic fatty liver disease (NAFLD). The current study was performed on yellow catfish, a good model to study NAFLD, and its hepatocytes to explore whether selenium (Se) could alleviate OFO-induced lipotoxicity\n                      <jats:italic toggle=\"yes\">via<\/jats:italic>\n                      the inhibition of oxidative stress and determine its potential mechanism.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      The analysis of triglycerides content, oxidative stress parameters, and histological and transmission electronic microscopy observation showed that high dietary Se supplementation alleviated OFO-induced lipotoxicity, oxidative stress, and mitochondrial injury and dysfunction. RNA-sequencing and immunoblotting analysis indicated that high dietary Se reduced OFO-induced decline of peroxisome-proliferator-activated receptor alpha (Ppar\u03b1) and ubiquitin-specific protease 4 (Usp4) protein expression. High Se supplementation also alleviated OFO-induced reduction of thioredoxin reductase 2 (\n                      <jats:italic toggle=\"yes\">txnrd2<\/jats:italic>\n                      ) messenger RNA (mRNA) expression level and activity. The\n                      <jats:italic toggle=\"yes\">txnrd2<\/jats:italic>\n                      knockdown experiments revealed that\n                      <jats:italic toggle=\"yes\">txnrd2<\/jats:italic>\n                      mediated Se- and oxidized eicosapentaenoic acid (oxEPA)-induced changes of mitochondrial reactive oxygen species (mtROS) and further altered Usp4 mediated-deubiquitination and stabilization of Ppar\u03b1, which, in turn, modulated mitochondrial fatty acid \u03b2-oxidation and metabolism. Mechanistically, Usp4 deubiquitinated Ppar\u03b1 and ubiquitin-proteasome-mediated Ppar\u03b1 degradation contributed to oxidative stress-induced mitochondrial dysfunction.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Innovation:<\/jats:title>\n                    <jats:p>\n                      These findings uncovered a previously unknown mechanism by which Se and OFO interacted to affect lipid metabolism\n                      <jats:italic toggle=\"yes\">via<\/jats:italic>\n                      the Txnrd2-mtROS-Usp4-Ppar\u03b1 pathway, which provides the new target for NAFLD prevention and treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      Se ameliorated OFO-induced lipotoxicity\n                      <jats:italic toggle=\"yes\">via<\/jats:italic>\n                      the inhibition of mitochondrial oxidative stress, remodeling of Usp4-mediated deubiquitination, and stabilization of Ppar\u03b1.\n                      <jats:italic toggle=\"yes\">Antioxid. Redox Signal.<\/jats:italic>\n                      40, 433\u2013452.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/ars.2022.0194","type":"journal-article","created":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T07:29:16Z","timestamp":1685690956000},"page":"433-452","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":19,"title":["Selenium Ameliorated Oxidized Fish Oil-Induced Lipotoxicity\n                    <i>via<\/i>\n                    the Inhibition of Mitochondrial Oxidative Stress, Remodeling of Usp4-Mediated Deubiquitination, and Stabilization of Ppar\u03b1"],"prefix":"10.1177","volume":"40","author":[{"given":"Dian-Guang","family":"Zhang","sequence":"first","affiliation":[{"name":"Shenzhen Institute of Nutrition and Health, Fishery College, Huazhong Agricultural University, Wuhan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfram S.","family":"Kunz","sequence":"additional","affiliation":[{"name":"Institute of Experimental Epileptology and Cognition Research, University of Bonn, Bonn, Germany."},{"name":"Department of Epileptology, University of Bonn, Bonn, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi-Jun","family":"Lei","sequence":"additional","affiliation":[{"name":"Shenzhen Institute of Nutrition and Health, Fishery College, Huazhong Agricultural University, Wuhan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ester","family":"Zito","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy."},{"name":"Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Zhao","sequence":"additional","affiliation":[{"name":"Shenzhen Institute of Nutrition and Health, Fishery College, Huazhong Agricultural University, Wuhan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Chuang","family":"Xu","sequence":"additional","affiliation":[{"name":"Shenzhen Institute of Nutrition and Health, Fishery College, Huazhong Agricultural University, Wuhan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Lei","family":"Wei","sequence":"additional","affiliation":[{"name":"Shenzhen Institute of Nutrition and Health, Fishery College, Huazhong Agricultural University, Wuhan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wu-Hong","family":"Lv","sequence":"additional","affiliation":[{"name":"Shenzhen Institute of Nutrition and Health, Fishery College, Huazhong Agricultural University, Wuhan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3219-1609","authenticated-orcid":false,"given":"Zhi","family":"Luo","sequence":"additional","affiliation":[{"name":"Shenzhen Institute of 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