2026-05-17T01:18:40Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/264092025-12-18T12:56:19Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Valdecantos, M Pilar
author
Ruiz, Laura
author
Folgueira, Cintia
author
Rada, Patricia
author
Gomez-Santos, Beatriz
author
Solas, Maite
author
Hitos, Ana B
author
Field, Joss
author
Francisco, Vera
author
Escalona-Garrido, Carmen
author
Zagmutt, Sebastián
author
Calderon-Dominguez, María
author
Mera, Paula
author
Garcia-Martinez, Irma
author
Maymó-Masip, Elsa
author
Grajales, Diana
author
Alen, Rosa
author
Mora, Alfonso
author
Sáinz, Neira
author
Vides-Urrestarazu, Irene
author
Vilarrasa, Nuria
author
Arbones-Mainar, José M
author
Zaragoza, Carlos
author
Moreno-Aliaga, María J
author
Aspichueta, Patricia
author
Fernández-Veledo, Sonia
author
Vendrell, Joan
author
Serra, Dolors
author
Herrero, Laura
author
Schreiber, Renate
author
Zechner, Rudolf
author
Sabio, Guadalupe
author
Hornigold, David
author
Rondinone, Cristina M
author
Jermutus, Lutz
author
Grimsby, Joseph
author
Valverde, Ángela M
funder
Ministerio de Ciencia, Innovación y Universidades (España)
funder
Asociación Española Contra el Cáncer
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Novo Nordisk Foundation
2025-03-10T16:32:10Z
2025-03-10T16:32:10Z
2024-11-28
Nat Commun. 2024 Nov 28;15(1):10342.
Nature Communications
39609390
https://hdl.handle.net/20.500.12105/26409
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.
eng
The dual GLP-1/glucagon receptor agonist G49 mimics bariatric surgery effects by inducing metabolic rewiring and inter-organ crosstalk.
research article
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URL
https://repisalud.isciii.es/bitstreams/0081400e-5a0b-4ed0-a880-6b9a47296f4e/download
File
MD5
4913c45897db924c3b70491af0580a2b
16691099
application/pdf
The dual GLP_1_Nat Commun_2024.pdf