Examinando por Autor "Keiran, Noelia"

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SUCNR1 controls an anti-inflammatory program in macrophages to regulate the metabolic response to obesity
(Nature, 2019-05) Keiran, Noelia; Ceperuelo-Mallafré, Victoria; Calvo, Enrique; Hernández-Alvarez, María isabel; Ejarque, Miriam; Núñez-Roa, Catalina; Hormillo, Daniel; Maymó-Masip, Elsa; Rodriguez, M Mar; Fradera, Rosa; de la Rosa, Juan Vladimir; Jorba, Rosa; Megia, Ana; Zorzano, Antonio; Medina-Gomez, Gema; Serena, Carolina; Castrillo, Antonio; Vendrell, Joan; Fernández-Veledo, Sonia
Succinate is a signaling metabolite sensed extracellularly by succinate receptor 1 (SUNCR1). The accumulation of succinate in macrophages is known to activate a pro-inflammatory program; however, the contribution of SUCNR1 to macrophage phenotype and function has remained unclear. Here we found that activation of SUCNR1 had a critical role in the anti-inflammatory responses in macrophages. Myeloid-specific deficiency in SUCNR1 promoted a local pro-inflammatory phenotype, disrupted glucose homeostasis in mice fed a normal chow diet, exacerbated the metabolic consequences of diet-induced obesity and impaired adipose-tissue browning in response to cold exposure. Activation of SUCNR1 promoted an anti-inflammatory phenotype in macrophages and boosted the response of these cells to type 2 cytokines, including interleukin-4. Succinate decreased the expression of inflammatory markers in adipose tissue from lean human subjects but not that from obese subjects, who had lower expression of SUCNR1 in adipose-tissue-resident macrophages. Our findings highlight the importance of succinate-SUCNR1 signaling in determining macrophage polarization and assign a role to succinate in limiting inflammation.