{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T18:20:25Z","timestamp":1790533225336,"version":"4.1.0"},"reference-count":63,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,2,7]],"date-time":"2020-02-07T00:00:00Z","timestamp":1581033600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"M\u0160MT, \u010cR","award":["Inter-Cost LTC17044"],"award-info":[{"award-number":["Inter-Cost LTC17044"]}]},{"DOI":"10.13039\/100007397","name":"Univerzita Karlova","doi-asserted-by":"publisher","award":["PROGRES Q40\/02"],"award-info":[{"award-number":["PROGRES Q40\/02"]}],"id":[{"id":"10.13039\/100007397","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Maladaptation of mitochondrial oxidative flux seems to be a considerable feature of nonalcoholic fatty liver disease (NAFLD). The aim of this work was to induce NAFLD in mice fed a Western-style diet (WD) and to evaluate liver mitochondrial functions. Experiments were performed on male C57BL\/6J mice fed with a control diet or a WD for 24 weeks. Histological changes in liver and adipose tissue as well as hepatic expression of fibrotic and inflammatory genes and proteins were evaluated. The mitochondrial respiration was assessed by high-resolution respirometry. Oxidative stress was evaluated by measuring lipoperoxidation, glutathione, and reactive oxygen species level. Feeding mice a WD induced adipose tissue inflammation and massive liver steatosis accompanied by mild inflammation and fibrosis. We found decreased succinate-activated mitochondrial respiration and decreased succinate dehydrogenase (SDH) activity in the mice fed a WD. The oxidative flux with other substrates was not affected. We observed increased ketogenic capacity, but no impact on the capacity for fatty acid oxidation. We did not confirm the presence of oxidative stress. Mitochondria in this stage of the disease are adapted to increased substrate flux. However, inhibition of SDH can lead to the accumulation of succinate, an important signaling molecule associated with inflammation, fibrosis, and carcinogenesis.<\/jats:p>","DOI":"10.3390\/ijms21031101","type":"journal-article","created":{"date-parts":[[2020,2,7]],"date-time":"2020-02-07T11:50:28Z","timestamp":1581076228000},"page":"1101","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Adaptation of Mitochondrial Substrate Flux in a Mouse Model of Nonalcoholic Fatty Liver Disease"],"prefix":"10.3390","volume":"21","author":[{"given":"Pavla","family":"Sta\u0148kov\u00e1","sequence":"first","affiliation":[{"name":"Department of Physiology, Faculty of Medicine in Hradec Kr\u00e1lov\u00e9, Charles University, \u0160imkova 870, 500 03 Hradec Kr\u00e1lov\u00e9, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5251-5343","authenticated-orcid":false,"given":"Otto","family":"Ku\u010dera","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine in Hradec Kr\u00e1lov\u00e9, Charles University, \u0160imkova 870, 500 03 Hradec Kr\u00e1lov\u00e9, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Peterov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Medicine in Hradec Kr\u00e1lov\u00e9, Charles University, \u0160imkova 870, 500 03 Hradec Kr\u00e1lov\u00e9, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Halka","family":"Lotkov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine in Hradec Kr\u00e1lov\u00e9, Charles University, \u0160imkova 870, 500 03 Hradec Kr\u00e1lov\u00e9, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tumisang Edward","family":"Maseko","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine in Hradec Kr\u00e1lov\u00e9, Charles University, \u0160imkova 870, 500 03 Hradec Kr\u00e1lov\u00e9, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate\u0159ina","family":"No\u017ei\u010dkov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine in Hradec Kr\u00e1lov\u00e9, Charles University, \u0160imkova 870, 500 03 Hradec Kr\u00e1lov\u00e9, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3908-290X","authenticated-orcid":false,"given":"Zuzana","family":"\u010cervinkov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine in Hradec Kr\u00e1lov\u00e9, Charles University, \u0160imkova 870, 500 03 Hradec Kr\u00e1lov\u00e9, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/hep.28431","article-title":"Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes","volume":"64","author":"Younossi","year":"2016","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2110","DOI":"10.4254\/wjh.v7.i17.2110","article-title":"Recent advances in mouse models of obesity- and nonalcoholic steatohepatitis-associated hepatocarcinogenesis","volume":"7","author":"Nakagawa","year":"2015","journal-title":"World J. 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