Intestinal group 1 innate lymphoid cells drive macrophage-induced inflammation and endocrine defects in obesity and promote insulinemia

Hypercaloric diets overactivate the intestinal immune system and disrupt the microbiome and epithelial cell functions, impairing glucose metabolism. The origins of this inflammatory cascade are poorly characterized. We investigated the involvement of intestinal proinflammatory group 1 innate lymphoi...

ver descrição completa

Detalhes bibliográficos
Autores: Liébana García, Rebeca, Olivares, Marta, Francés Cuesta, Carlos, Rubio, Teresa, Rossini, Valerio, Quintas, Guillermo, Sanz Herranz, Yolanda
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/297043
Acesso em linha:http://hdl.handle.net/10261/297043
https://api.elsevier.com/content/abstract/scopus_id/85148843720
Access Level:acceso abierto
Palavra-chave:Akkermansia muciniphila
ILC1s
Microbiota
High-sucrose high-fat diet
Metabolism
Obesity
http://metadata.un.org/sdg/3
Ensure healthy lives and promote well-being for all at all ages
Descrição
Resumo:Hypercaloric diets overactivate the intestinal immune system and disrupt the microbiome and epithelial cell functions, impairing glucose metabolism. The origins of this inflammatory cascade are poorly characterized. We investigated the involvement of intestinal proinflammatory group 1 innate lymphoid cells (ILC1s) in obesity progression and metabolic disruption. In obese mice, we studied longitudinally the ILC1s response to the diet and ILC1s depletion to address its role in obesity. ILC1s are required for the expansion of pro-inflammatory macrophages and ILC2s. ILC1s depletion induced the ILC3-IL-22 pathway, increasing mucin production, antimicrobial peptides, and neuroendocrine cells. These changes were translated into higher gut hormones and reduced insulinemia and adiposity. ILC1s depletion was also associated with a bloom in Akkermansia muciniphila and decreases in Bilophila spp. Intestinal-ILC1s are upstream activators of inflammatory signals, connecting immunity with the microbiome, the enteroendocrine system, and the intestinal barrier in the control of glucose metabolism and adiposity.