{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T19:46:25Z","timestamp":1780602385788,"version":"3.54.1"},"reference-count":75,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,31]],"date-time":"2022-12-31T00:00:00Z","timestamp":1672444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of University (MIUR)","award":["PRIN 2009: 200928EEX4"],"award-info":[{"award-number":["PRIN 2009: 200928EEX4"]}]},{"name":"Italian Ministry of University (MIUR)","award":["2017 2017YH3SXK"],"award-info":[{"award-number":["2017 2017YH3SXK"]}]},{"name":"Italian Ministry of University (MIUR)","award":["PRIN 2009: 2009HST9YF"],"award-info":[{"award-number":["PRIN 2009: 2009HST9YF"]}]},{"name":"Italian Ministry of University (MIUR)","award":["POC01_00069"],"award-info":[{"award-number":["POC01_00069"]}]},{"name":"Italian Ministry of University and Research (MUR)","award":["PRIN 2009: 200928EEX4"],"award-info":[{"award-number":["PRIN 2009: 200928EEX4"]}]},{"name":"Italian Ministry of University and Research (MUR)","award":["2017 2017YH3SXK"],"award-info":[{"award-number":["2017 2017YH3SXK"]}]},{"name":"Italian Ministry of University and Research (MUR)","award":["PRIN 2009: 2009HST9YF"],"award-info":[{"award-number":["PRIN 2009: 2009HST9YF"]}]},{"name":"Italian Ministry of University and Research (MUR)","award":["POC01_00069"],"award-info":[{"award-number":["POC01_00069"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Fenofibrate (FBR), an oral medication used to treat dyslipidemia, is a ligand of the peroxisome proliferator-activated receptor \u03b1 (PPAR\u03b1), a nuclear receptor that regulates the expression of metabolic genes able to control lipid metabolism and food intake. PPAR\u03b1 natural ligands include fatty acids (FA) and FA derivatives such as palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), known to have anti-inflammatory and anorexigenic activities, respectively. We investigated changes in the FA profile and FA derivatives by HPLC and LC-MS in male C57BL\/6J mice fed a standard diet with or without 0.2% fenofibrate (0.2% FBR) for 21 days. Induction of PPAR\u03b1 by 0.2% FBR reduced weight gain, food intake, feed efficiency, and liver lipids and induced a profound change in FA metabolism mediated by parallel enhanced mitochondrial and peroxisomal \u03b2-oxidation. The former effects led to a steep reduction of essential FA, particularly 18:3n3, with a consequent decrease of the n3-highly unsaturated fatty acids (HUFA) score; the latter effect led to an increase of 16:1n7 and 18:1n9, suggesting enhanced hepatic de novo lipogenesis with increased levels of hepatic PEA and OEA, which may activate a positive feedback and further sustain reductions of body weight, hepatic lipids and feed efficiency.<\/jats:p>","DOI":"10.3390\/ijms24010709","type":"journal-article","created":{"date-parts":[[2023,1,2]],"date-time":"2023-01-02T04:07:09Z","timestamp":1672632429000},"page":"709","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Profound Modification of Fatty Acid Profile and Endocannabinoid-Related Mediators in PPAR\u03b1 Agonist Fenofibrate-Treated Mice"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7394-5780","authenticated-orcid":false,"given":"Elisabetta","family":"Murru","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, University of Cagliari, 09042 Monserrato, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1546-9509","authenticated-orcid":false,"given":"Anna Lisa","family":"Muntoni","sequence":"additional","affiliation":[{"name":"Neuroscience Institute, Section of Cagliari, National Research Council of Italy, 09042 Monserrato, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4081-9550","authenticated-orcid":false,"given":"Claudia","family":"Manca","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Cagliari, 09042 Monserrato, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Aroni","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Cagliari, 09042 Monserrato, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4622-3205","authenticated-orcid":false,"given":"Marco","family":"Pistis","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Cagliari, 09042 Monserrato, Italy"},{"name":"Neuroscience Institute, Section of Cagliari, National Research Council of Italy, 09042 Monserrato, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4805-1387","authenticated-orcid":false,"given":"Sebastiano","family":"Banni","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Cagliari, 09042 Monserrato, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3527-4197","authenticated-orcid":false,"given":"Gianfranca","family":"Carta","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Cagliari, 09042 Monserrato, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1186\/1475-2840-11-125","article-title":"Fibrates Are an Essential Part of Modern Anti-Dyslipidemic Arsenal: Spotlight on Atherogenic Dyslipidemia and Residual Risk Reduction","volume":"11","author":"Tenenbaum","year":"2012","journal-title":"Cardiovasc. 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