The novel chimeric multi-agonist peptide (GEP44) reduces energy intake and body weight in male and female diet-induced obese mice in a glucagon-like peptide-1 receptor-dependent manner

Autor: James E. Blevins, Mackenzie K. Honeycutt, Jared D. Slattery, Matvey Goldberg, June R. Rambousek, Edison Tsui, Andrew D. Dodson, Kyra A. Shelton, Therese S. Salemeh, Clinton T. Elfers, Kylie S. Chichura, Emily F. Ashlaw, Sakeneh Zraika, Robert P. Doyle, Christian L. Roth
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Frontiers in Endocrinology, Vol 15 (2024)
Druh dokumentu: article
ISSN: 1664-2392
DOI: 10.3389/fendo.2024.1432928
Popis: We recently reported that a novel chimeric peptide (GEP44) targeting both the glucagon-like peptide-1 receptor (GLP-1R) and neuropeptide Y1- and Y2 receptor (Y1R and Y2R) reduced energy intake and body weight (BW) in diet-induced obese (DIO) rats. We hypothesized that GEP44 reduces energy intake and BW primarily through a GLP-1R dependent mechanism. To test this hypothesis, GLP-1R+/+ mice and GLP-1R null (GLP-1R-/-) mice were fed a high fat diet for 4 months to elicit diet-induced obesity prior to undergoing a sequential 3-day vehicle period, 3-day drug treatment (5, 10, 20 or 50 nmol/kg; GEP44 vs the selective GLP-1R agonist, exendin-4) and a 3-day washout. Energy intake, BW, core temperature and activity were measured daily. GEP44 (10, 20 and 50 nmol/kg) reduced BW after 3-day treatment in DIO male GLP-1R+/+ mice by -1.5 ± 0.6, -1.3 ± 0.4 and -1.9 ± 0.4 grams, respectively (P
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