{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T13:39:14Z","timestamp":1791812354790,"version":"4.3.4"},"reference-count":33,"publisher":"The Endocrine Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,3,1]]},"abstract":"<jats:p>Peroxisome proliferator-activated receptors (PPARs) are transcription factors involved in the regulation of numerous metabolic processes. The PPAR\u03b1 isotype is abundant in liver and activated by fasting. However, it is not very clear what other nutritional conditions activate PPAR\u03b1. To examine whether PPAR\u03b1 mediates the effects of chronic high-fat feeding, wild-type and PPAR\u03b1 null mice were fed a low-fat diet (LFD) or high-fat diet (HFD) for 26 wk. HFD and PPAR\u03b1 deletion independently increased liver triglycerides. Furthermore, in wild-type mice HFD was associated with a significant increase in hepatic PPAR\u03b1 mRNA and plasma free fatty acids, leading to a PPAR\u03b1-dependent increase in expression of PPAR\u03b1 marker genes CYP4A10 and CYP4A14. Microarray analysis revealed that HFD increased hepatic expression of characteristic PPAR\u03b1 target genes involved in fatty acid oxidation in a PPAR\u03b1-dependent manner, although to a lesser extent than fasting or Wy14643. Microarray analysis also indicated functional compensation for PPAR\u03b1 in PPAR\u03b1 null mice. Remarkably, in PPAR\u03b1 null mice on HFD, PPAR\u03b3 mRNA was 20-fold elevated compared with wild-type mice fed a LFD, reaching expression levels of PPAR\u03b1 in normal mice. Adenoviral overexpression of PPAR\u03b3 in liver indicated that PPAR\u03b3 can up-regulate genes involved in lipo\/adipogenesis but also characteristic PPAR\u03b1 targets involved in fatty acid oxidation. It is concluded that 1) PPAR\u03b1 and PPAR\u03b1-signaling are activated in liver by chronic high-fat feeding; and 2) PPAR\u03b3 may compensate for PPAR\u03b1 in PPAR\u03b1 null mice on HFD.<\/jats:p>","DOI":"10.1210\/en.2005-1132","type":"journal-article","created":{"date-parts":[[2005,12,15]],"date-time":"2005-12-15T20:25:05Z","timestamp":1134678305000},"page":"1508-1516","source":"Crossref","is-referenced-by-count":303,"title":["Peroxisome Proliferator-Activated Receptor \u03b1 Mediates the Effects of High-Fat Diet on Hepatic Gene Expression"],"prefix":"10.1210","volume":"147","author":[{"given":"David","family":"Patsouris","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janardan 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