Gut HIF2α signaling is increased after VSG, and gut activation of HIF2α decreases weight, improves glucose, and increases GLP-1 secretion.
Cell Rep
; 38(3): 110270, 2022 01 18.
Article
en En
| MEDLINE
| ID: mdl-35045308
ABSTRACT
Gastric bypass and vertical sleeve gastrectomy (VSG) remain the most potent and durable treatments for obesity and type 2 diabetes but are also associated with iron deficiency. The transcription factor HIF2α, which regulates iron absorption in the duodenum, increases following these surgeries. Increasing iron levels by means of dietary supplementation or hepatic hepcidin knockdown does not undermine the effects of VSG, indicating that metabolic improvements following VSG are not secondary to lower iron levels. Gut-specific deletion of Vhl results in increased constitutive duodenal HIF2α signaling and produces a profound lean, glucose-tolerant phenotype that mimics key effects of VSG. Interestingly, intestinal Vhl deletion also results in increased intestinal secretion of GLP-1, which is essential for these metabolic benefits. These data demonstrate a role for increased duodenal HIF2α signaling in regulating crosstalk between iron-regulatory systems and other aspects of systemic physiology important for metabolic regulation.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Gastroplastia
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Duodeno
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Péptido 1 Similar al Glucagón
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico
Idioma:
En
Revista:
Cell Rep
Año:
2022
Tipo del documento:
Article