2026-05-17T01:18:36Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/264092025-12-18T12:56:19Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc 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 author 2024-11-28 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. Nat Commun. 2024 Nov 28;15(1):10342. Nature Communications 39609390 https://hdl.handle.net/20.500.12105/26409 The dual GLP-1/glucagon receptor agonist G49 mimics bariatric surgery effects by inducing metabolic rewiring and inter-organ crosstalk.