The dual GLP-1/glucagon receptor agonist G49 mimics bariatric surgery effects by inducing metabolic rewiring and inter-organ cross-talk

Bariatric surgery is effective for the treatment and remission of obesity and type 2 diabetes, but pharmacological approaches which exert similar metabolic adaptations are needed to avoid post-surgical complications. Here we show how G49, an oxyntomodulin (OXM) analog and dual glucagon/glucagon-like...

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Detalles Bibliográficos
Autores: Valdecantos, M. Pilar, Ruiz, Laura, Folgueira, Cintia, Rada, Patricia, Gómez-Santos, Beatriz, Solas, Maite, Hitos, Ana B., Field, Joss, Francisco, Vera, Escalona-Garrido, Carmen, Zagmutt Caroxa, Sebastián, Calderón Domínguez, María, Mera Nanín, Paula, García Martínez, Irma, Maymó Masip, Elsa, Grajales, Diana, Alen, Rosa, Mora, Alfonso, Sainz, Neira, Vides-Urrestarazu, Irene, Vilarrasa, Nuria, Arbones-Mainar, Jose M., Zaragoza, Carlos, Moreno-Aliaga, María J., Aspichueta, Patricia, Fernández Veledo, Sonia, Vendrell, Joan, Serra i Cucurull, Dolors, Herrero Rodríguez, Laura, Schreiber, Renate, Zechner, Rudolf, Sabio, Guadalupe, Hornigold, David, Rondinone, Cristina M., Jermutus, Lutz, Grimsby, Joseph, Valverde, Ángela M.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/220136
Acceso en línea:https://hdl.handle.net/2445/220136
Access Level:acceso abierto
Palabra clave:Diabetis
Síndrome metabòlica
Glucagó
Obesitat
Diabetes
Metabolic syndrome
Glucagon
Obesity
Descripción
Sumario:Bariatric surgery is effective for the treatment and remission of obesity and type 2 diabetes, but pharmacological approaches which exert similar metabolic adaptations are needed to avoid post-surgical complications. Here we show how G49, an oxyntomodulin (OXM) analog and dual glucagon/glucagon-like peptide-1 receptor (GCGR/GLP-1R) agonist, triggers an inter-organ crosstalk between adipose tissue, pancreas, and liver which is initiated by a rapid release of free fatty acids (FFAs) by white adipose tissue (WAT) in a GCGR-dependent manner. This interactome leads to elevations in adiponectin and fibroblast growth factor 21 (FGF21), causing WAT beiging, brown adipose tissue (BAT) activation, increased energy expenditure (EE) and weight loss. Elevation of OXM, under basal and postprandial conditions, and similar metabolic adaptations after G49 treatment were found in plasma from patients with obesity early after metabolic bariatric surgery. These results identify G49 as a potential pharmacological alternative sharing with bariatric surgery hormonal and metabolic pathways.

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