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

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, Gomez-Santos, Beatriz, Solas, Maite, Hitos, Ana B., Field, Joss, Francisco, Vera, Escalona-Garrido, Carmen, Zagmutt, Sebastián, Calderon-Dominguez, María, Mera, Paula, Garcia-Martinez, Irma, Maymó-Masip, Elsa, Grajales, Diana, Alen, Rosa, Mora, Alfonso, Sáinz, Neira, Vides-Urrestarazu, Irene, Vilarrasa, Nuria, Arbones-Mainar, José M., Zaragoza, Carlos, Moreno-Aliaga, María J., Aspichueta, Patricia, Fernández-Veledo, Sonia, Vendrell, Joan, Serra, Dolors, Herrero, Laura, Schreiber, Renate, Zechner, Rudolf, Sabio, Guadalupe, Hornigold, David, Rondinone, Cristina M., Jermutus, Lutz, Grimsby, Joseph, Valverde, Ángela M.
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universidad Francisco de Vitoria
Repositorio:DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria
Idioma:inglés
OAI Identifier:oai:ddfv.ufv.es:10641/7544
Acceso en línea:https://hdl.handle.net/10641/7544
Access Level:acceso abierto
Palabra clave:General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy
SDG 3 - Good Health and Well-being
Journal Article
Research Support, Non-U.S. Gov't
Yes
yes
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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