A Receptor of the Immunoglobulin Superfamily Regulates Adaptive Thermogenesis

Exquisite regulation of energy homeostasis protects from nutrient deprivation but causes metabolic dysfunction upon nutrient excess. In human and murine adipose tissue, the accumulation of ligands of the receptor for advanced glycation end products (RAGE) accompanies obesity, implicating this recept...

Descripción completa

Detalles Bibliográficos
Autores: Hurtado del Pozo, Carmen, Ruiz, Henry, Arivazhagan, Lakshmi, Aranda Gómez, Juan Francisco, Shim, Cynthia, Daya, Peter, Derk, Julia, MacLean, Michael, He, Meilun, Frye, Laura, Randall, Friedline, Hye, Lim Noh, Kim, Jason, Friedman, Richard, Ramasamy, Ravichandran, Schmidt, Ann Marie
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/95020
Acceso en línea:https://hdl.handle.net/20.500.14352/95020
Access Level:acceso abierto
Palabra clave:611.018.26
Adaptive thermogenesis
Adipocyte
Adipose tissue
Cold tolerance
Obesity
Protein kinase A
Receptor for advanced glycation end products
RAGE
Signal transduction
Advanced glycation end products
Bioquímica (Biología)
2403 Bioquímica
Descripción
Sumario:Exquisite regulation of energy homeostasis protects from nutrient deprivation but causes metabolic dysfunction upon nutrient excess. In human and murine adipose tissue, the accumulation of ligands of the receptor for advanced glycation end products (RAGE) accompanies obesity, implicating this receptor in energy metabolism. Here, we demonstrate that mice bearing global- or adipocyte-specific deletion of Ager, the gene encoding RAGE, display superior metabolic recovery after fasting, a cold challenge, or high-fat feeding. The RAGE-dependent mechanisms were traced to suppression of protein kinase A (PKA)-mediated phosphorylation of its key targets, hormone-sensitive lipase and p38 mitogen-activated protein kinase, upon β-adrenergic receptor stimulation—processes that dampen the expression and activity of uncoupling protein 1 (UCP1) and thermogenic programs. This work identifies the innate role of RAGE as a key node in the immunometabolic networks that control responses to nutrient supply and cold challenges, and it unveils opportunities to harness energy expenditure in environmental and metabolic stress.

Similares en LA Referencia