{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T02:02:39Z","timestamp":1793325759126,"version":"4.5.0"},"reference-count":37,"publisher":"American Physiological Society","issue":"1","funder":[{"DOI":"10.13039\/100000062","name":"HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)","doi-asserted-by":"publisher","award":["DK102572"],"award-info":[{"award-number":["DK102572"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2018,1,1]]},"abstract":"<jats:p>\n                    Peroxisome proliferator-activated receptor \u03b1 (PPAR\u03b1) is a nuclear hormone receptor that promotes fatty acid \u03b2-oxidation (FAO) and oxidative phosphorylation (OXPHOS). We and others have recently shown that PPAR\u03b1 and its target genes are downregulated, and FAO and OXPHOS are impaired in autosomal dominant polycystic kidney disease (ADPKD). However, whether PPAR\u03b1 and FAO\/OXPHOS are causally linked to ADPKD progression is not entirely clear. We report that expression of PPAR\u03b1 and FAO\/OXPHOS genes is downregulated, and in vivo \u03b2-oxidation rate of\n                    <jats:sup>3<\/jats:sup>\n                    H-labeled triolein is reduced in Pkd1\n                    <jats:sup>RC\/RC<\/jats:sup>\n                    mice, a slowly progressing orthologous model of ADPKD that closely mimics the human ADPKD phenotype. To evaluate the effects of upregulating PPAR\u03b1, we conducted a 5-mo, randomized, preclinical trial by treating Pkd1\n                    <jats:sup>RC\/RC<\/jats:sup>\n                    mice with fenofibrate, a clinically available PPAR\u03b1 agonist. Fenofibrate treatment resulted in increased expression of PPAR\u03b1 and FAO\/OXPHOS genes, upregulation of peroxisomal and mitochondrial biogenesis markers, and higher \u03b2-oxidation rates in Pkd1\n                    <jats:sup>RC\/RC<\/jats:sup>\n                    kidneys. MRI-assessed total kidney volume and total cyst volume, kidney-weight-to-body-weight ratio, cyst index, and serum creatinine levels were significantly reduced in fenofibrate-treated compared with untreated littermate Pkd1\n                    <jats:sup>RC\/RC<\/jats:sup>\n                    mice. Moreover, fenofibrate treatment was associated with reduced kidney cyst proliferation and infiltration by inflammatory cells, including M2-like macrophages. Finally, fenofibrate treatment also reduced bile duct cyst number, cyst proliferation, and liver inflammation and fibrosis. In conclusion, our studies suggest that promoting PPAR\u03b1 activity to enhance mitochondrial metabolism may be a useful therapeutic strategy for ADPKD.\n                  <\/jats:p>","DOI":"10.1152\/ajprenal.00352.2017","type":"journal-article","created":{"date-parts":[[2017,9,13]],"date-time":"2017-09-13T21:00:39Z","timestamp":1505336439000},"page":"F122-F131","source":"Crossref","is-referenced-by-count":143,"title":["PPAR\u03b1 agonist fenofibrate enhances fatty acid \u03b2-oxidation and attenuates polycystic kidney and liver disease in mice"],"prefix":"10.1152","volume":"314","author":[{"given":"Ronak","family":"Lakhia","sequence":"first","affiliation":[{"name":"Department of Internal Medicine and Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matanel","family":"Yheskel","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Division of Nephrology, 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