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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...

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Detalles Bibliográficos
Autores principales: del Pozo, Carmen Hurtado, Ruiz, Henry H., Arivazhagan, Lakshmi, Aranda, Juan Francisco, Shim, Cynthia, Daya, Peter, Derk, Julia, MacLean, Michael, He, Meilun, Frye, Laura, Friedline, Randall H., Noh, Hye Lim, Kim, Jason K., Friedman, Richard A., Ramasamy, Ravichandran, Schmidt, Ann Marie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6686683/
https://www.ncbi.nlm.nih.gov/pubmed/31315054
http://dx.doi.org/10.1016/j.celrep.2019.06.061
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.