Author, as appears in the article.: Cabre, Noemi; Luciano-Mateo, Fedra; Chapski, Douglas J.; Baiges-Gaya, Gerard; Fernandez-Arroyo, Salvador; Hernandez-Aguilera, Anna; Castane, Helena; Rodriguez-Tomas, Elisabet; Paris, Marta; Sabench, Fatima; Del Castillo, Daniel; del Bas, Josep M.; Tome, Mercedes; Bodineau, Clement; Sola-Garcia, Alejandro; Lopez-Miranda, Jose; Martin-Montalvo, Alejandro; Duran, Raul, V; Vondriska, Thomas M.; Rosa-Garrido, Manuel; Camps, Jordi; Menendez, Javier A.; Joven, Jorge;
Department: Medicina i Cirurgia
URV's Author/s: Baiges Gaya, Gerard / Camps Andreu, Jorge / Castañé Vilafranca, Helena / Del Castillo Déjardin, Daniel / FERNANDEZ ARROYO, SALVADOR / Joven Maried, Jorge / París Sans, Marta / Rodriguez Tomas, Elisabet / Sabench Pereferrer, Fàtima
Keywords: Signatures Multi-omics approach Morbid-obesity Metabolomics Glutaminolysis Functional studies Fatty liver Epigenetics Energy metabolism Dna methylation Bariatric surgery Alpha-ketoglutarate Adaptation
Abstract: The surgically induced remission of liver disease represents a model to investigate the signalling processes that trigger the development of nonalcoholic steatohepatitis with the aim of identifying novel therapeutic targets. We recruited patients with severe obesity with or without nonalcoholic steatohepatitis and obtained liver and plasma samples before and after laparoscopic sleeve gastrectomy for immunoblotting, immunocytochemical, metabolomic, transcriptomic and epigenetic analyses. Functional studies were performed in HepG2 cells and primary hepatocytes. Surgery was associated with a decrease in the inflammatory response and revealed the role of mitogen-activated protein kinases. Nonalcoholic steatohepatitis was associated with an increased glutaminolysis-induced production of alpha-ketoglutarate and the hyperactivation of mammalian target of rapamycin complex 1. These changes were crucial for adenosine monophosphate-activated protein kinase/mammalian target of rapamycin-driven pathways that modulated hepatocyte survival by coordinating apoptosis and autophagy and affected methylation-related epigenomic remodelling enzymes. Hepatic transcriptome signatures and differentially methylated genomic regions distinguished patients with and without steatohepatitis. Our results suggest that the increased glutaminolysis-induced alpha-ketoglutarate production and the mammalian target of rapamycin complex 1 dysregulation play a crucial role in the inefficient adaptive responses leading to steatohepatitis in obesity.
Thematic Areas: Zootecnia / recursos pesqueiros Spectroscopy Saúde coletiva Química Psicología Physical and theoretical chemistry Organic chemistry Odontología Nutrição Molecular biology Medicine (miscellaneous) Medicina veterinaria Medicina iii Medicina ii Medicina i Materiais Interdisciplinar Inorganic chemistry Geociências Farmacia Engenharias iv Engenharias ii Engenharias i Educação física Computer science applications Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciências ambientais Ciências agrárias i Ciência de alimentos Ciência da computação Chemistry, multidisciplinary Catalysis Biotecnología Biodiversidade Biochemistry & molecular biology Astronomia / física
licence for use: https://creativecommons.org/licenses/by/3.0/es/
Author's mail: marta.paris@urv.cat jorge.camps@urv.cat danieldel.castillo@urv.cat helena.castane@estudiants.urv.cat gerard.baiges@estudiants.urv.cat elisabet.rodriguezt@estudiants.urv.cat elisabet.rodriguezt@estudiants.urv.cat jorge.joven@urv.cat fatima.sabench@urv.cat
Author identifier: 0000-0002-3165-3640 0000-0003-0456-3102 0000-0001-7024-7824 0000-0003-2749-4541 0000-0002-9262-8756
Record's date: 2024-09-07
Papper version: info:eu-repo/semantics/publishedVersion
Link to the original source: https://www.mdpi.com/1422-0067/23/14/7830
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Papper original source: International Journal Of Molecular Sciences. 23 (14):
APA: Cabre, Noemi; Luciano-Mateo, Fedra; Chapski, Douglas J.; Baiges-Gaya, Gerard; Fernandez-Arroyo, Salvador; Hernandez-Aguilera, Anna; Castane, Helena; R (2022). Laparoscopic Sleeve Gastrectomy in Patients with Severe Obesity Restores Adaptive Responses Leading to Nonalcoholic Steatohepatitis. International Journal Of Molecular Sciences, 23(14), -. DOI: 10.3390/ijms23147830
Article's DOI: 10.3390/ijms23147830
Entity: Universitat Rovira i Virgili
Journal publication year: 2022
Publication Type: Journal Publications
Repositori URV