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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.
Blevins, James E; Honeycutt, Mackenzie K; Slattery, Jared D; Goldberg, Matvey; Rambousek, June R; Tsui, Edison; Dodson, Andrew D; Shelton, Kyra A; Salemeh, Therese S; Elfers, Clinton T; Chichura, Kylie S; Ashlaw, Emily F; Zraika, Sakeneh; Doyle, Robert P; Roth, Christian L.
Afiliación
  • Blevins JE; VA Puget Sound Health Care System, Office of Research and Development Medical Research Service, Department of Veterans Affairs Medical Center, Seattle, WA, United States.
  • Honeycutt MK; Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington School of Medicine, Seattle, WA, United States.
  • Slattery JD; VA Puget Sound Health Care System, Office of Research and Development Medical Research Service, Department of Veterans Affairs Medical Center, Seattle, WA, United States.
  • Goldberg M; VA Puget Sound Health Care System, Office of Research and Development Medical Research Service, Department of Veterans Affairs Medical Center, Seattle, WA, United States.
  • Rambousek JR; VA Puget Sound Health Care System, Office of Research and Development Medical Research Service, Department of Veterans Affairs Medical Center, Seattle, WA, United States.
  • Tsui E; VA Puget Sound Health Care System, Office of Research and Development Medical Research Service, Department of Veterans Affairs Medical Center, Seattle, WA, United States.
  • Dodson AD; VA Puget Sound Health Care System, Office of Research and Development Medical Research Service, Department of Veterans Affairs Medical Center, Seattle, WA, United States.
  • Shelton KA; VA Puget Sound Health Care System, Office of Research and Development Medical Research Service, Department of Veterans Affairs Medical Center, Seattle, WA, United States.
  • Salemeh TS; VA Puget Sound Health Care System, Office of Research and Development Medical Research Service, Department of Veterans Affairs Medical Center, Seattle, WA, United States.
  • Elfers CT; Seattle Children's Research Institute, Seattle, WA, United States.
  • Chichura KS; Seattle Children's Research Institute, Seattle, WA, United States.
  • Ashlaw EF; Department of Chemistry, Syracuse University, Syracuse, NY, United States.
  • Zraika S; Department of Chemistry, Syracuse University, Syracuse, NY, United States.
  • Doyle RP; VA Puget Sound Health Care System, Office of Research and Development Medical Research Service, Department of Veterans Affairs Medical Center, Seattle, WA, United States.
  • Roth CL; Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington School of Medicine, Seattle, WA, United States.
Front Endocrinol (Lausanne) ; 15: 1432928, 2024.
Article en En | MEDLINE | ID: mdl-39104812
ABSTRACT
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<0.05), with similar effects being observed in female GLP-1R+/+ mice. These effects were absent in male and female DIO GLP-1R-/- mice suggesting that GLP-1R signaling contributes to GEP44-elicited reduction of BW. Further, GEP44 decreased energy intake in both male and female DIO GLP-1R+/+ mice, but GEP44 appeared to produce more consistent effects across multiple doses in males. In GLP-1R-/- mice, the effects of GEP44 on energy intake were only observed in males and not females, suggesting that GEP44 may reduce energy intake, in part, through a GLP-1R independent mechanism in males. In addition, GEP44 reduced core temperature and activity in both male and female GLP-1R+/+ mice suggesting that it may also reduce energy expenditure. Lastly, we show that GEP44 reduced fasting blood glucose in DIO male and female mice through GLP-1R. Together, these findings support the hypothesis that the chimeric peptide, GEP44, reduces energy intake, BW, core temperature, and glucose levels in male and female DIO mice primarily through a GLP-1R dependent mechanism.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Peso Corporal / Ingestión de Energía / Dieta Alta en Grasa / Receptor del Péptido 1 Similar al Glucagón / Ratones Obesos / Obesidad Límite: Animals Idioma: En Revista: Front Endocrinol (Lausanne) Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
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PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Peso Corporal / Ingestión de Energía / Dieta Alta en Grasa / Receptor del Péptido 1 Similar al Glucagón / Ratones Obesos / Obesidad Límite: Animals Idioma: En Revista: Front Endocrinol (Lausanne) Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza