Autor segons l'article: Arto, Carmen; Rusu, Elena Cristina; Clavero-Mestres, Helena; Barrientos-Riosalido, Andrea; Bertran, Laia; Mahmoudian, Razieh; Aguilar, Carmen; Riesco, David; Chicote, Javier Ugarte; Parada, David; Martinez, Salome; Sabench, Fatima; Richart, Cristobal; Auguet, Teresa
Departament: Ciències Mèdiques Bàsiques Medicina i Cirurgia
Autor/s de la URV: Aguilar Crespillo, Carmen Isabel / Auguet Quintillà, Maria Teresa / Barrientos Riosalido, Andrea / Bertran Ramos, Laia / Clavero Mestres, Helena / Parada Dominguez, David / Richart Jurado, Cristobal Manuel / Riesco Acevedo, David Gerardo / Sabench Pereferrer, Fàtima
Paraules clau: Tryptophan Tryptopha System Serotonin Obesity, morbid Obesity Nafl Middle aged Metabolic dysfunction‐associated steatotic liver disease Metabolic dysfunction-associated steatotic liver disease Male Liver Kynurenine pathway Kynurenine 3-monooxygenase Kynurenine Inflammatory response Indoles Indolepropionic acid Indoleamine-pyrrole 2,3,-dioxygenase Indoleacetic acids Indoleacetic acid Indole Immune activation Ido1 protein, human Humans Health Gut microbiota Fibrosis Female Fatty liver Case-control studies Biomarkers Adult
Resum: Background and AimsThe rise in obesity highlights the need for improved therapeutic strategies, particularly in addressing metabolic dysfunction-associated steatotic liver disease (MASLD). We aim to assess the role of tryptophan metabolic pathways in the pathogenesis of obesity and in the different histological stages of MASLD.Materials and MethodsWe used ultra-high performance liquid chromatography to quantify circulating levels of 15 tryptophan-related 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-associated steatohepatitis (MASH). Then, we conducted gene expression analysis of hepatic IDO-1 and kynyrenine-3-monooxygenase (KMO).ResultsKey findings in obesity revealed a distinct metabolic signature characterized by a higher concentration of different kynurenine-related metabolites, a decrease in indole-3-acetic acid and indole-3-propionic acid, and an alteration in the serotonin pathway. Elevated tryptophan levels were associated with MASLD presence (37.659 (32.577-39.823) mu M of tryptophan in NL subjects; 41.522 (38.803-45.276) mu M 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-1 and KMO hepatic expression in NL compared to SS.ConclusionsWe identified a distinctive metabolic signature in obesity marked by changes in tryptophan catabolic pathways, discernible through altered metabolite profiles. We observed stage-specific alterations in tryptophan catabolism fluxes in MASLD, highlighting the potential utility of targeting these pathways in therapeutic interventions. The study delves into tryptophan pathways in obesity and metabolic dysfunction-associated steatotic liver disease. Fifteen tryptophan-related metabolites were determined in 76 subjects, spanning normal weight and morbid obesity cohorts categorized by liver condition. Gene expression of hepatic IDO-1 and kynyrenine-3-monooxygenase (KMO) was analysed. We found distinct signatures in obesity: increased kynurenine cascade, decreased indole route and altered serotonin pathway. Reduced hepatic expression of IDO-1 and KMO is noted in normal liver versus simple steatosis. Tryptophan catabolism shifts across histological stagesimage
Àrees temàtiques: Saúde coletiva Odontología Nutrição Medicine, research & experimental Medicine, general & internal Medicine (miscellaneous) Medicina ii Medicina i Interdisciplinar General medicine Farmacia Educação física Clinical biochemistry Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Biotecnología Biochemistry
Accès a la llicència d'ús: https://creativecommons.org/licenses/by/3.0/es/
Adreça de correu electrònic de l'autor: andrea.barrientos@urv.cat andrea.barrientos@urv.cat davidgerardo.riesco@urv.cat david.parada@urv.cat cristobalmanuel.richart@urv.cat helena.clavero@urv.cat laia.bertranr@estudiants.urv.cat laia.bertranr@estudiants.urv.cat fatima.sabench@urv.cat carmenisabel.aguilar@urv.cat carmenisabel.aguilar@urv.cat mariateresa.auguet@urv.cat
Identificador de l'autor: 0000-0003-0852-6739 0000-0001-9052-1368 0000-0001-9052-1368 0000-0002-9262-8756 0000-0002-4440-562X 0000-0002-4440-562X https://orcid.org/0000-0003-0396-6428 0000-0003-0396-6428
Data d'alta del registre: 2025-03-03
Versió de l'article dipositat: info:eu-repo/semantics/publishedVersion
Referència a l'article segons font original: European Journal Of Clinical Investigation. 54 (11): e14279-e14279
Referència de l'ítem segons les normes APA: Arto, Carmen; Rusu, Elena Cristina; Clavero-Mestres, Helena; Barrientos-Riosalido, Andrea; Bertran, Laia; Mahmoudian, Razieh; Aguilar, Carmen; Riesco, (2024). Metabolic profiling of tryptophan pathways: Implications for obesity and metabolic dysfunction-associated steatotic liver disease. European Journal Of Clinical Investigation, 54(11), e14279-e14279. DOI: 10.1111/eci.14279
URL Document de llicència: https://repositori.urv.cat/ca/proteccio-de-dades/
Entitat: Universitat Rovira i Virgili
Any de publicació de la revista: 2024
Tipus de publicació: Journal Publications
Repositori URV