{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T16:55:50Z","timestamp":1781283350741,"version":"3.54.1"},"reference-count":35,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T00:00:00Z","timestamp":1771632000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T00:00:00Z","timestamp":1771632000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK117144"],"award-info":[{"award-number":["R01DK117144"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["24TPA1278431"],"award-info":[{"award-number":["24TPA1278431"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR002243"],"award-info":[{"award-number":["UL1TR002243"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR000445"],"award-info":[{"award-number":["UL1TR000445"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Endocrino Diabet &amp;amp; Metabol"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Higher circulating levels of the metabolite alpha\u2010aminoadipic acid (2\u2010AAA) associate with increased risk of diabetes and cardiometabolic disease. 2\u2010AAA is metabolised from lysine, an essential dietary amino acid. However, the effects of lysine intake on plasma levels of 2\u2010AAA were unclear. We measured post\u2010prandial changes in plasma and urine levels of 2\u2010AAA in healthy individuals in response to oral intake of\n                      <jats:sup>13<\/jats:sup>\n                      C isotope\u2010labelled lysine and assessed relationships with markers of glucose homeostasis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We recruited healthy individuals (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u200916) to an acute lysine challenge. We administered 5\u2009g of\n                      <jats:sup>13<\/jats:sup>\n                      C Lysine\u2010HCL in 50\u2009mL water as an oral bolus. We measured the appearance of\n                      <jats:sup>13<\/jats:sup>\n                      C lysine and\n                      <jats:sup>13<\/jats:sup>\n                      C 2\u2010AAA in plasma and urine over a period of 6 h post\u2010ingestion and assessed changes in insulin, C\u2010peptide, glucagon, and GLP\u20101.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found that\n                      <jats:sup>13<\/jats:sup>\n                      C lysine and\n                      <jats:sup>13<\/jats:sup>\n                      C 2\u2010AAA were detectable in plasma 30\u2009min post\u2010ingestion, peaking on average 2 h post\u2010ingestion. Interestingly, non\u2010labelled lysine and non\u2010labelled 2\u2010AAA also increased. Individuals with higher plasma levels of\n                      <jats:sup>13<\/jats:sup>\n                      C 2\u2010AAA post\u2010ingestion also had higher levels of\n                      <jats:sup>13<\/jats:sup>\n                      C 2\u2010AAA in urine. The rate of appearance of 2\u2010AAA in plasma and excretion in urine differed between individuals and was associated with differences in waist\u2010to\u2010hip ratio (WHR). We observed increases in plasma insulin, C\u2010peptide, glucagon, and GLP\u20101 post\u2010lysine ingestion.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our data suggest that orally ingested lysine is catabolised to 2\u2010AAA over several hours. However, lysine ingestion also stimulates an increase in 2\u2010AAA from endogenous sources. The rate of production and excretion differs between individuals, suggestive of controlled regulation of this metabolic pathway. Individuals with a higher WHR, indicative of greater visceral adiposity, may have increased excretion of 2\u2010AAA, tryptophan, and kynurenine.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/edm2.70168","type":"journal-article","created":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T09:30:00Z","timestamp":1771666200000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Response of Alpha\u2010Aminoadipic Acid (2\u2010AAA) to Short Term Lysine Ingestion in Healthy Individuals"],"prefix":"10.1002","volume":"9","author":[{"given":"E. Danielle","family":"Dean","sequence":"first","affiliation":[{"name":"Division of Diabetes, Endocrinology and Metabolism Vanderbilt University Medical Center  Nashville Tennessee USA"},{"name":"Department of Molecular Physiology and Biophysics Vanderbilt University  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacy","family":"Desine","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly M.","family":"Smith","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda C.","family":"Doran","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan D.","family":"Mosley","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Wade","family":"Calcutt","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Mass Spectrometry Research Center, Vanderbilt University  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6896-1025","authenticated-orcid":false,"given":"Jane F.","family":"Ferguson","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000001209"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2019.00016"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI64801"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc16\u20101875"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2017.03.002"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1122391"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.121.024388"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(76)80288-4"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2016.09.006"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/nxaa224"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2017.01.006"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.numecd.2024.03.009"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.2337\/db23\u20100977"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.2337\/dbi19\u20100021"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE\u201023\u20100081"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbi.2008.08.010"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbi.2019.103208"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3109\/00365517709101835"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424\u2010009\u20100638\u20102"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST20140176"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2015.02.003"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3305"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadva.2023.100075"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201807204"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgab272"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1128\/aem.60.6.1705\u20101710.1994"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1999.277.4.E597"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajcnut.2024.05.010"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0089728"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0135437"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3809"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201700323R"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.2337\/db22\u20100079"},{"key":"e_1_2_9_35_1","doi-asserted-by":"crossref","unstructured":"E.Spears J. 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