{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T06:04:23Z","timestamp":1792821863000,"version":"4.5.0"},"reference-count":0,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,5,30]],"date-time":"2024-05-30T00:00:00Z","timestamp":1717027200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Acute pancreatitis (AP) entails pancreatic inflammation, tissue damage and dysregulated enzyme secretion, including pancreatic lipase (PL). The role of irisin, an anti-inflammatory and anti-apoptotic cytokine, in AP and exocrine pancreatic stress is unclear. We have previously shown that irisin regulates PL through the PPAR\u03b3-PGC1\u03b1-FNDC5 pathway. In this study, we investigated irisin and irisin\u2019s pathway on AP in in vitro (AR42J-B13) and ex vivo (rat primary acinar) models using molecular, biochemical and immunohistochemistry methodology. Pancreatitis induction (cerulein (cer)) resulted in a significant up-regulation of the PPAR\u03b3-PGC1\u03b1-FNDC5 axis, PL expression and secretion and endoplasmic reticulum (ER) stress unfolded protein response (UPR) signal-transduction markers (CHOP, XBP-1 and ATF6). Irisin addition in the cer-pancreatitis state resulted in a significant down-regulation of the PPAR\u03b3-PGC1\u03b1-FNDC5 axis, PPAR\u03b3 nucleus-translocation and inflammatory state (TNF\u03b1 and IL-6) in parallel to diminished PL expression and secretion (in vitro and ex vivo models). Irisin addition up-regulated the expression of pro-survival UPR markers (ATF6 and XBP-1) and reduced UPR pro-apoptotic markers (CHOP) under cer-pancreatitis and induced ER stress (tunicamycin), consequently increasing cells viability. Irisin\u2019s pro-survival effect under cer-pancreatitis state was abolished under PPAR\u03b3 inhibition. Our findings suggest irisin as a potential therapeutic option for AP via its ability to up-regulate pro-survival UPR signals and activate the PPAR\u03b3-PGC1\u03b1-FNDC5 pathway.<\/jats:p>","DOI":"10.3390\/biom14060643","type":"journal-article","created":{"date-parts":[[2024,5,31]],"date-time":"2024-05-31T06:35:32Z","timestamp":1717137332000},"page":"643","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Irisin Ameliorate Acute Pancreatitis and Acinar Cell Viability through Modulation of the Unfolded Protein Response (UPR) and PPAR\u03b3-PGC1\u03b1-FNDC5 Pathways"],"prefix":"10.3390","volume":"14","author":[{"given":"Avital","family":"Horwitz","sequence":"first","affiliation":[{"name":"Nutrition Department, Faculty of Health Sciences, Ariel University, Ariel 40700, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5770-4277","authenticated-orcid":false,"given":"Ruth","family":"Birk","sequence":"additional","affiliation":[{"name":"Nutrition Department, Faculty of Health Sciences, Ariel University, Ariel 40700, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,30]]},"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/14\/6\/643\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:51:12Z","timestamp":1760107872000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/14\/6\/643"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,30]]},"references-count":0,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["biom14060643"],"URL":"https:\/\/doi.org\/10.3390\/biom14060643","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,30]]}}}