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We aim to assess the role of tryptophan metabolic pathways in the pathogenesis of obesity and in the different histological stages of MASLD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>We used ultra\u2010high performance liquid chromatography to quantify circulating levels of 15 tryptophan\u2010related metabolites from the kynurenine, indole and serotonin pathways. A cohort of 76 subjects was analysed, comprising 18 subjects with normal weight and 58 with morbid obesity, these last being subclassified into normal liver (NL), simple steatosis (SS) and metabolic dysfunction\u2010associated steatohepatitis (MASH). Then, we conducted gene expression analysis of hepatic IDO\u20101 and kynyrenine\u20103\u2010monooxygenase (KMO).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Key findings in obesity revealed a distinct metabolic signature characterized by a higher concentration of different kynurenine\u2010related metabolites, a decrease in indole\u20103\u2010acetic acid and indole\u20103\u2010propionic acid, and an alteration in the serotonin pathway. Elevated tryptophan levels were associated with MASLD presence (37.659 (32.577\u201339.823) \u03bcM of tryptophan in NL subjects; 41.522 (38.803\u201345.276) \u03bcM in patients with MASLD). Overall, pathway fluxes demonstrated an induction of tryptophan catabolism via the serotonin pathway in SS subjects and into the kynurenine pathway in MASH. We found decreased IDO\u20101 and KMO hepatic expression in NL compared to SS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We identified a distinctive metabolic signature in obesity marked by changes in tryptophan catabolic pathways, discernible through altered metabolite profiles. We observed stage\u2010specific alterations in tryptophan catabolism fluxes in MASLD, highlighting the potential utility of targeting these pathways in therapeutic interventions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/eci.14279","type":"journal-article","created":{"date-parts":[[2024,6,28]],"date-time":"2024-06-28T06:10:34Z","timestamp":1719555034000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Metabolic profiling of tryptophan pathways: Implications for obesity and metabolic dysfunction\u2010associated steatotic liver disease"],"prefix":"10.1111","volume":"54","author":[{"given":"Carmen","family":"Arto","sequence":"first","affiliation":[{"name":"Servei Medicina Interna Hospital Sant Pau i Santa Tecla de Tarragona  Tarragona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena Cristina","family":"Rusu","sequence":"additional","affiliation":[{"name":"Departament de 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