{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T16:08:57Z","timestamp":1792080537441,"version":"4.4.0"},"reference-count":43,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,5,19]],"date-time":"2022-05-19T00:00:00Z","timestamp":1652918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"SAPIENZA University","award":["R11816433B8F7F8"],"award-info":[{"award-number":["R11816433B8F7F8"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Adelmidrol is a promising palmitoylethanolamide (PEA) analog which displayed up-and-coming anti-inflammatory properties in several inflammatory conditions. Recent studies demonstrated that Adelmidrol is an in vitro enhancer of PEA endogenous production, through the so called \u201centourage\u201d effect. The present study investigated the ability of Adelmidrol (1 and 10 mg\/Kg per os) to increase the endogenous level of PEA in the duodenum and colon of mice after 21-day oral administration in the presence and absence of PPAR-\u03b3 inhibitor (1 mg\/kg). The level of PEA was analyzed by HPLC-MS. The expression of PEA-related enzymatic machinery was evaluated by western blot and RT-PCR analysis. Our findings demonstrated that Adelmidrol significantly increased PEA levels in the duodenum and colon in a dose\/time-dependent manner. We also revealed that Adelmidrol up regulated the enzymatic machinery responsible for PEA metabolism and catabolism. Interestingly, the use of the selective irreversible PPAR-\u03b3 antagonist did not affect either PEA intestinal levels or expression\/transcription of PEA metabolic enzymes following Adelmidrol administration. The \u201centourage effect\u201d with Adelmidrol as an enhancer of PEA was thus PPAR-\u03b3-independent. The findings suggest that Adelmidrol can maximize a PEA therapeutic-based approach in several intestinal morbidities.<\/jats:p>","DOI":"10.3390\/metabo12050457","type":"journal-article","created":{"date-parts":[[2022,5,20]],"date-time":"2022-05-20T00:18:11Z","timestamp":1653005891000},"page":"457","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Oral Adelmidrol Administration Up-Regulates Palmitoylethanolamide Production in Mice Colon and Duodenum through a PPAR-\u03b3 Independent Action"],"prefix":"10.3390","volume":"12","author":[{"given":"Alessandro","family":"Del Re","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology V. Erspamer, Sapienza University of Rome, Piazzale AldoMoro 5, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5019-653X","authenticated-orcid":false,"given":"Irene","family":"Palenca","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology V. Erspamer, Sapienza University of Rome, Piazzale AldoMoro 5, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2346-9912","authenticated-orcid":false,"given":"Luisa","family":"Seguella","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology V. Erspamer, Sapienza University of Rome, Piazzale AldoMoro 5, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5996-4259","authenticated-orcid":false,"given":"Marcella","family":"Pesce","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Corpetti","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology V. Erspamer, Sapienza University of Rome, Piazzale AldoMoro 5, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Steardo","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Giustino Fortunato University, 82100 Benevento, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Rurgo","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1467-1134","authenticated-orcid":false,"given":"Giovanni","family":"Sarnelli","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8080-8218","authenticated-orcid":false,"given":"Giuseppe","family":"Esposito","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology V. Erspamer, Sapienza University of Rome, Piazzale AldoMoro 5, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Sarnelli, G., D\u2019Alessandro, A., Iuvone, T., Capoccia, E., Gigli, S., Pesce, M., Seguella, L., Nobile, N., Aprea, G., and Maione, F. (2016). Palmitoylethanolamide Modulates Inflammation-Associated Vascular Endothelial Growth Factor (VEGF) Signaling via the Akt\/mTOR Pathway in a Selective Peroxisome Proliferator-Activated Receptor Alpha (PPAR-\u03b1)-Dependent Manner. 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