{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T11:10:15Z","timestamp":1790334615101,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":267,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100005564","name":"Gilead Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005564","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["PPAR Research"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Seladelpar, a potent and selective peroxisome proliferator\u2010activated receptor\u2010\n                      <jats:italic>\u03b4<\/jats:italic>\n                      (PPAR\n                      <jats:italic>\u03b4<\/jats:italic>\n                      ) agonist, is an approved second\u2010line therapy for primary biliary cholangitis (PBC) in patients with an inadequate response or intolerance to ursodeoxycholic acid (UDCA). In clinical studies, seladelpar significantly improved biochemical markers associated with disease progression and pruritus. Our objective was to explore the metabolic mechanisms underlying seladelpar\u2032s effects and identify potential biomarkers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Untargeted serum metabolomic analyses were conducted using UHPLC\u2010MS\/MS on fasting samples from 160 patients with PBC, collected before and after 12 weeks of treatment with placebo (\n                      <jats:italic>n<\/jats:italic>\n                      = 55), seladelpar 5\u2009mg (\n                      <jats:italic>n<\/jats:italic>\n                      = 52), or seladelpar 10\u2009mg (\n                      <jats:italic>n<\/jats:italic>\n                      = 53) in a randomized, placebo\u2010controlled Phase 3 study (NCT03602560).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 1474 metabolites were identified from global untargeted serum metabolomics analysis. Random forest, weighted correlation network analysis, and differential abundance analysis revealed significant metabolomic changes after seladelpar treatment. Notable changes included significant increases in carnitine, acetylcarnitine, other acylcarnitines, and branched\u2010chain amino acid catabolites as well as significant decreases in dicarboxylates, saturated and unsaturated fatty acids, and lipid\u2010derived inflammatory mediators including ceramides. Targeted metabolomics confirmed seladelpar\u2032s impact on carnitine and acylcarnitines, which facilitate fatty acid\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010oxidation. Gene expression analysis of primary human hepatocytes and mouse tissues showed upregulation of carnitine transporter and mitochondrial carnitine shuttle genes with seladelpar treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Seladelpar treatment of PBC patients resulted in broad changes in serum metabolites, many of which are downstream of known PPAR\n                      <jats:italic>\u03b4<\/jats:italic>\n                      activation effects, including peroxisomal and mitochondrial fatty acid\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010oxidation. This comprehensive metabolomics analysis highlights potential pathways for future exploration in the treatment of PBC and its symptoms.\n                    <\/jats:p>\n                    <jats:p>\n                      <jats:bold>Trial Registration:<\/jats:bold>\n                      ClinicalTrials.gov identifier: NCT03602560; EudraCT number: 2018\u2010001171\u201020\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/ppar\/2362528","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T10:44:51Z","timestamp":1790333091000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Serum Metabolomic Profiling Reveals Potential Mechanisms and Biomarkers of Seladelpar Treatment in Patients With Primary Biliary Cholangitis"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5153-9714","authenticated-orcid":false,"given":"Yun-Jung","family":"Choi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1517-4308","authenticated-orcid":false,"given":"Andrew","family":"Schwab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8968-4300","authenticated-orcid":false,"given":"Samantha M.","family":"Carlisle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7613-3008","authenticated-orcid":false,"given":"Charles A.","family":"McWherter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9384-9577","authenticated-orcid":false,"given":"Jeffrey 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