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To find new PPAR ligands with fewer toxic effects, we generated transgenic zebrafish that can be screened in high throughput for new tissue-selective PPAR partial agonists. A structural analog of coenzyme Q10 (idebenone) that elicits spatially restricted partial agonist activity for both PPAR\u03b1 and PPAR\u03b3 was identified. Coenzyme Q10 was also found to bind and activate both PPARs in a similar fashion, suggesting an endogenous role in relaying the states of mitochondria, peroxisomes and cellular redox to the two receptors. Testing idebenone in a mouse model of type 2 diabetes revealed the ability to reverse fatty liver development. These findings indicate new mechanisms of action for both PPAR\u03b1 and PPAR\u03b3, and new potential treatment options for nonalcoholic fatty liver disease (NAFLD) and steatosis.<\/jats:p>\n               <jats:p>This article has an associated First Person interview with the first author of the paper.<\/jats:p>","DOI":"10.1242\/dmm.034801","type":"journal-article","created":{"date-parts":[[2018,8,31]],"date-time":"2018-08-31T10:25:13Z","timestamp":1535711113000},"source":"Crossref","is-referenced-by-count":38,"title":["Idebenone and coenzyme Q10 are novel PPAR\u03b1\/\u03b3 ligands, with potential for treatment of fatty liver diseases"],"prefix":"10.1242","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4941-4477","authenticated-orcid":false,"given":"Jens","family":"Tiefenbach","sequence":"first","affiliation":[{"name":"University of Toronto 1 , Donnelly Ctr., 160 College St , Toronto, ON \u2008 M5S 3E1 , Canada"},{"name":"InDanio Bioscience Inc. 2 , 160 College Street, Toronto, ON \u2008 M5S 3E1 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8151-1424","authenticated-orcid":false,"given":"Lilia","family":"Magomedova","sequence":"additional","affiliation":[{"name":"Leslie Dan Faculty of Pharmacy, 144 College St, University of Toronto 3 Department of Pharmaceutical Sciences , , Toronto, ON \u2008 M5S 3M2 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5440-1841","authenticated-orcid":false,"given":"Jiabao","family":"Liu","sequence":"additional","affiliation":[{"name":"University of Toronto 1 , Donnelly Ctr., 160 College St , Toronto, ON \u2008 M5S 3E1 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arkadiy A.","family":"Reunov","sequence":"additional","affiliation":[{"name":"InDanio Bioscience Inc. 2 , 160 College Street, Toronto, ON \u2008 M5S 3E1 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricky","family":"Tsai","sequence":"additional","affiliation":[{"name":"Leslie Dan Faculty of Pharmacy, 144 College St, University of Toronto 3 Department of Pharmaceutical Sciences , , Toronto, ON \u2008 M5S 3M2 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neena S.","family":"Eappen","sequence":"additional","affiliation":[{"name":"University of Toronto 4 Department of Chemistry, 80 St George St , , Toronto, ON \u2008 M5S 3H4 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8192-7486","authenticated-orcid":false,"given":"Rebecca A.","family":"Jockusch","sequence":"additional","affiliation":[{"name":"University of Toronto 4 Department of Chemistry, 80 St George St , , Toronto, ON \u2008 M5S 3H4 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4016-8874","authenticated-orcid":false,"given":"Corey","family":"Nislow","sequence":"additional","affiliation":[{"name":"The University of British Columbia 5 , Faculty of Pharmaceutical Sciences, 2405 Wesbrook Mall, Vancouver, BC \u2008 V6T 1Z3 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7603-6577","authenticated-orcid":false,"given":"Carolyn L.","family":"Cummins","sequence":"additional","affiliation":[{"name":"Leslie Dan Faculty of Pharmacy, 144 College St, University of Toronto 3 Department of Pharmaceutical Sciences , , Toronto, ON \u2008 M5S 3M2 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6182-7074","authenticated-orcid":false,"given":"Henry M.","family":"Krause","sequence":"additional","affiliation":[{"name":"University of Toronto 1 , Donnelly Ctr., 160 College St , Toronto, ON \u2008 M5S 3E1 , Canada"},{"name":"InDanio Bioscience Inc. 2 , 160 College Street, Toronto, ON \u2008 M5S 3E1 , Canada"},{"name":"University of Toronto 6 Department of Molecular Genetics , , Toronto, ON M5S 1A8 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2018,8,31]]},"reference":[{"key":"2024061303521813300_DMM034801C1","doi-asserted-by":"publisher","first-page":"124","DOI":"10.2174\/187152512800388948","article-title":"PPAR- gamma agonist in treatment of diabetes: cardiovascular safety considerations","volume":"10","author":"Abbas","year":"2012","journal-title":"Cardiovasc. 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