{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:27:12Z","timestamp":1792099632548,"version":"4.4.0"},"reference-count":65,"publisher":"American Society for Clinical Investigation","issue":"1","license":[{"start":{"date-parts":[[2025,1,2]],"date-time":"2025-01-02T00:00:00Z","timestamp":1735776000000},"content-version":"vor","delay-in-days":56,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["RO1DK092460,R01DK119646,R01AA031257"],"award-info":[{"award-number":["RO1DK092460,R01DK119646,R01AA031257"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"U.S. Department of Defense","award":["PR191945 under W81XWH-20-1-0400"],"award-info":[{"award-number":["PR191945 under W81XWH-20-1-0400"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,2]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>While most hypertriglyceridemia is asymptomatic, hypertriglyceridemia-associated acute pancreatitis (HTG-AP) can be more severe than AP of other etiologies. The reasons underlying this are unclear. We thus examined whether lipolytic generation of nonesterified fatty acids (NEFAs) from circulating triglycerides (TGs) could worsen clinical outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Admission serum TGs, NEFA composition, and concentrations were analyzed prospectively for 269 patients with AP. These parameters, demographics, and clinical outcomes were compared between HTG-AP (TGs &gt;500 mg\/dL; American Heart Association [AHA] 2018 guidelines) and AP of other etiologies. Serum NEFAs were correlated with serum TG fatty acids (TGFAs) alone and with the product of TGFA serum lipase (NEFAs \u2013 TGFAs \u00d7 lipase). Studies in mice and rats were conducted to understand the role of HTG lipolysis in organ failure and to interpret the NEFA-TGFA correlations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Patients with HTG-AP had higher serum NEFA and TG levels and more severe AP (19% vs. 7%;\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.03) than did individuals with AP of other etiologies. Correlations of long-chain unsaturated NEFAs with corresponding TGFAs increased with TG concentrations up to 500 mg\/dL and declined thereafter. However, NEFA \u2013 TGFA \u00d7 lipase correlations became stronger with TGs above 500 mg\/dL. AP and intravenous lipase infusion in rodents caused lipolysis of circulating TGs to NEFAs. This led to multisystem organ failure, which was prevented by pancreatic TG lipase deletion or lipase inhibition.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>HTG-AP is made severe by the NEFAs generated from intravascular lipolysis of circulating TGs. Strategies that prevent TG lipolysis may be effective in improving clinical outcomes for patients with HTG-AP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>FUNDING<\/jats:title>\n                    <jats:p>National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK, NIH) (RO1DK092460 and R01DK119646); Department of Defense (PR191945 under W81XWH-20-1-0400); National Institute on Alcohol Abuse and Alcoholism (NIAAA), NIH (R01AA031257).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1172\/jci184785","type":"journal-article","created":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T13:14:35Z","timestamp":1730985275000},"source":"Crossref","is-referenced-by-count":26,"title":["Prospective observational study and mechanistic evidence showing lipolysis of circulating triglycerides worsens hypertriglyceridemic acute pancreatitis"],"prefix":"10.1172","volume":"135","author":[{"given":"Prasad","family":"Rajalingamgari","sequence":"first","affiliation":[{"name":"Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0464-2321","authenticated-orcid":true,"given":"Biswajit","family":"Khatua","sequence":"additional","affiliation":[{"name":"Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan J.","family":"Summers","sequence":"additional","affiliation":[{"name":"Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergiy","family":"Kostenko","sequence":"additional","affiliation":[{"name":"Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Hui H.","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Clinical Trials and Biostatistics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Elmallahy","sequence":"additional","affiliation":[{"name":"Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arti","family":"Anand","sequence":"additional","affiliation":[{"name":"Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anoop","family":"Narayana Pillai","sequence":"additional","affiliation":[{"name":"Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud","family":"Morsy","sequence":"additional","affiliation":[{"name":"Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0526-7970","authenticated-orcid":true,"given":"Shubham","family":"Trivedi","sequence":"additional","affiliation":[{"name":"Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8074-7953","authenticated-orcid":true,"given":"Bryce","family":"McFayden","sequence":"additional","affiliation":[{"name":"Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Jahangir","sequence":"additional","affiliation":[{"name":"Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine L.H.","family":"Snozek","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijay P.","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Medicine,"},{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic, Arizona, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2024,11,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pan.2020.03.018"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pan.2019.06.006"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-74943-8"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-32337-x"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1097\/MCG.0000000000000846"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.pan.2016.02.011"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1186\/s12944-017-0517-3"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2015.261"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1006\/jsre.2000.5925"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.20317"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2018.12.041"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3402\/jchimp.v6.31808"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0165309"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1111\/apha.13916"},{"issue":"1","key":"B15","first-page":"60","article-title":"Acute pancreatitis with hyperlipemia: studies with an isolated perfused canine pancreas","volume":"82","author":"Saharia","year":"1977","journal-title":"Surgery"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1159\/000055816"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1007\/BF02786078"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00074.2023"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1172\/JCI132767"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.104322"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2023.05.034"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2014-308043"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abd6449"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.05.057"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)39591-2"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/14.5.280"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2021.07.029"},{"issue":"14","key":"B28","first-page":"40","article-title":"The enzymatic synthesis of triglycerides","volume":"235","author":"Weiss","year":"1956","journal-title":"J Biol Chem"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000624"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2012-302779"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1172\/JCI40659"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.104322"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.hpb.2019.01.015"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1186\/s12944-019-1126-0"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-74943-8"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0121945"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3200\/JEXE.71.1.53-70"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3002573"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2014.02.015"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0102748"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1097\/MEG.0000000000001399"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2023.20802"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1097\/MCG.0000000000000552"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1097\/MPA.0b013e3181bd6370"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1159\/000097949"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/S0899-9007(01)00755-9"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2015.158"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1186\/s12944-020-01302-x"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijsu.2015.08.080"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacl.2016.02.019"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1097\/00006676-199907000-00002"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1159\/000134273"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.pan.2019.08.002"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1159\/000512682"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1016\/j.pan.2021.10.001"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1136\/bmjdrc-2022-003070"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2013.218"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1097\/00006676-199704000-00001"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.15288\/jsad.2014.75.530"},{"key":"B60","article-title":"A man with primary hyperchylomicronemia with triglyceride levels exceeding 11,000 mg\/dL was well controlled by pemafibrate combined with dietary therapy: a case report","author":"Ueda","journal-title":"Intern Med"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1016\/j.pan.2020.02.010"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1038\/srep40799"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1177\/0192623310394212"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0804091105"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-017-4609-6"}],"container-title":["Journal of Clinical Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jci.org\/articles\/view\/184785\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T22:46:56Z","timestamp":1779230816000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jci.org\/articles\/view\/184785"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,7]]},"references-count":65,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1,2]]},"published-print":{"date-parts":[[2025,1,2]]}},"alternative-id":["10.1172\/JCI184785"],"URL":"https:\/\/doi.org\/10.1172\/jci184785","relation":{},"ISSN":["1558-8238"],"issn-type":[{"value":"1558-8238","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,7]]},"article-number":"e184785"}}