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Visualization and Quantification of Brown and Beige Adipose Tissues in Mice using [18F]FDG Micro-PET/MR Imaging
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La adenosina activa el tejido adiposo marrón y recluta adipocitos beige a través de los receptores A2A
Thorsten Gnad1, Saskia Scheibler2, Ivar von Kügelgen1
1Institute of Pharmacology and Toxicology, University Hospital, University of Bonn, 53127 Bonn, Germany.
Nature
|October 16, 2014
Resumen
La adenosina activa el tejido adiposo marrón (BAT) a través de los receptores A2A, aumentando el gasto energético. Este descubrimiento ofrece nuevas estrategias terapéuticas para la obesidad y los trastornos metabólicos.
Área de la Ciencia:
- Metabolismo y Endocrinología.
- Biología celular Biología celular.
- Investigación de la obesidad.
Sus antecedentes:
- El tejido adiposo marrón (TAB) es crucial para el gasto energético y un objetivo para las terapias antiobesidad.
- Las actuales estrategias de activación de las MTD (agonistas beta-adrenérgicos fríos) tienen limitaciones clínicas.
- El papel de la señalización de la adenosina en la función de las MTD en humanos seguía siendo en gran medida desconocido.
Objetivo del estudio:
- Investigar el papel de la adenosina y sus receptores en el tejido adiposo marrón humano y murino.
- Explorar la señalización de la adenosina como un objetivo terapéutico potencial para la obesidad.
Principales métodos:
- Investigó el efecto de la adenosina en los adipocitos marrones humanos y murinos in vitro.
- Liberación de adenosina medida durante la estimulación del nervio simpático.
- Se analizó la expresión y la función de los receptores de adenosina en las MTD utilizando enfoques genéticos y farmacológicos en ratones.
- Se evaluó el impacto de la modulación del receptor A2A en la termogénesis, el gasto energético y la obesidad inducida por la dieta.
Principales resultados:
- La adenosina activa los adipocitos marrones humanos y murinos en concentraciones nanomolares.
- La adenosina se libera de la MTD durante la estimulación del nervio simpático.
- El receptor de adenosina A2A está altamente expresado en las MTD y media los efectos de la adenosina.
- La activación del receptor A2A aumenta la termogénesis BAT, el gasto de energía e induce la formación de adipocitos beige.
- El tratamiento con agonistas A2A en ratones redujo la obesidad y mejoró la tolerancia a la glucosa en condiciones de dieta alta en grasas.
Conclusiones:
- La señalización del receptor de adenosina-A2A juega un papel fisiológico crítico en la activación simpática de las MTD.
- Dirigirse al receptor de adenosina A2A representa una nueva estrategia prometedora para el desarrollo de terapias contra la obesidad.
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