Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/17677
Título
Inhibition of the IL-17A axis in adipocytes suppresses diet-induced obesity and metabolic disorders in mice.
Autor(es)
Fecha de publicación
2021-04
Cita
Nat Metab . 2021;3(4):496-512
Idioma
Inglés
Tipo de documento
journal article
Resumen
Overnutrition causes obesity, a global health problem without any effective therapy. Obesity is characterized by low-grade inflammation, which predisposes individuals to metabolic syndrome via unknown mechanisms. Here, we demonstrate that abolishing the interleukin-17A (IL-17A) axis in mice by inhibition of RORγt-mediated IL-17A production by digoxin, or by ubiquitous deletion of IL-17 receptor A (Il17ra), suppresses diet-induced obesity (DIO) and metabolic disorders, and promotes adipose-tissue browning, thermogenesis and energy expenditure. Genetic ablation of Il17ra specifically in adipocytes is sufficient to completely prevent DIO and metabolic dysfunction in mice. IL-17A produced in response to DIO induces PPARγ phosphorylation at Ser273 in adipocytes in a CDK5-dependent manner, thereby modifying expression of diabetogenic and obesity genes, which correlates with IL-17A signalling in white adipose tissues of individuals with morbid obesity. These findings reveal an unanticipated role for IL-17A in adipocyte biology, in which its direct action pathogenically reprograms adipocytes, promoting DIO and metabolic syndrome. Targeting the IL-17A axis could be an efficient antiobesity strategy.
MESH
Adipocytes | Adipose Tissue, Brown | Animals | Cyclin-Dependent Kinase 5 | Diet | Diet, High-Fat | Digoxin | Energy Metabolism | Feces | Gene Deletion | Interleukin-17 | Metabolic Diseases | Mice | Mice, Inbred C57BL | Mice, Knockout | Nuclear Receptor Subfamily 1, Group F, Member 3 | Obesity | Overnutrition | PPAR gamma | Phosphorylation | Thermogenesis
Versión en línea
DOI
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Ficheros en el ítem
- Nombre:
- InhibitionoftheIL-17Aaxis_2021.docx
- Tamaño:
- 245.0Kb
- Formato:
- Microsoft Word 2007
- Descripción:
- Preprint