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Metabolic and gut microbiome changes following GLP-1 or dual GLP-1/GLP-2 receptor agonist treatment in diet-induced obese mice.
Madsen, Mette Simone Aae; Holm, Jacob Bak; Pallejà, Albert; Wismann, Pernille; Fabricius, Katrine; Rigbolt, Kristoffer; Mikkelsen, Martin; Sommer, Morten; Jelsing, Jacob; Nielsen, Henrik Bjørn; Vrang, Niels; Hansen, Henrik H.
Afiliación
  • Madsen MSA; Gubra, Hørsholm, Denmark.
  • Holm JB; Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kgs. Lyngby, Denmark.
  • Pallejà A; Clinical Microbiomics, Ole Maaløes Vej 3, Copenhagen, Denmark.
  • Wismann P; Clinical Microbiomics, Ole Maaløes Vej 3, Copenhagen, Denmark.
  • Fabricius K; Gubra, Hørsholm, Denmark.
  • Rigbolt K; Gubra, Hørsholm, Denmark.
  • Mikkelsen M; Gubra, Hørsholm, Denmark.
  • Sommer M; Gubra, Hørsholm, Denmark.
  • Jelsing J; Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kgs. Lyngby, Denmark.
  • Nielsen HB; Gubra, Hørsholm, Denmark.
  • Vrang N; Clinical Microbiomics, Ole Maaløes Vej 3, Copenhagen, Denmark.
  • Hansen HH; Gubra, Hørsholm, Denmark.
Sci Rep ; 9(1): 15582, 2019 10 30.
Article en En | MEDLINE | ID: mdl-31666597
Enteroendocrine L-cell derived peptide hormones, notably glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2), have become important targets in the treatment of type 2 diabetes, obesity and intestinal diseases. As gut microbial imbalances and maladaptive host responses have been implicated in the pathology of obesity and diabetes, this study aimed to determine the effects of pharmacologically stimulated GLP-1 and GLP-2 receptor function on the gut microbiome composition in diet-induced obese (DIO) mice. DIO mice received treatment with a selective GLP-1 receptor agonist (liraglutide, 0.2 mg/kg, BID) or dual GLP-1/GLP-2 receptor agonist (GUB09-145, 0.04 mg/kg, BID) for 4 weeks. Both compounds suppressed caloric intake, promoted a marked weight loss, improved glucose tolerance and reduced plasma cholesterol levels. 16S rDNA sequencing and deep-sequencing shotgun metagenomics was applied for comprehensive within-subject profiling of changes in gut microbiome signatures. Compared to baseline, DIO mice assumed phylogenetically similar gut bacterial compositional changes following liraglutide and GUB09-145 treatment, characterized by discrete shifts in low-abundant species and related bacterial metabolic pathways. The microbiome alterations may potentially associate to the converging biological actions of GLP-1 and GLP-2 receptor signaling on caloric intake, glucose metabolism and lipid handling.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Dieta / Receptor del Péptido 1 Similar al Glucagón / Receptor del Péptido 2 Similar al Glucagón / Microbioma Gastrointestinal / Obesidad Límite: Animals Idioma: En Revista: Sci Rep Año: 2019 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Dieta / Receptor del Péptido 1 Similar al Glucagón / Receptor del Péptido 2 Similar al Glucagón / Microbioma Gastrointestinal / Obesidad Límite: Animals Idioma: En Revista: Sci Rep Año: 2019 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Reino Unido