Functional Gut Microbiota Remodeling Contributes to the Caloric Restriction-Induced Metabolic Improvements.
Cell Metab
; 28(6): 907-921.e7, 2018 12 04.
Article
em En
| MEDLINE
| ID: mdl-30174308
ABSTRACT
Caloric restriction (CR) stimulates development of functional beige fat and extends healthy lifespan. Here we show that compositional and functional changes in the gut microbiota contribute to a number of CR-induced metabolic improvements and promote fat browning. Mechanistically, these effects are linked to a lower expression of the key bacterial enzymes necessary for the lipid A biosynthesis, a critical lipopolysaccharide (LPS) building component. The decreased LPS dictates the tone of the innate immune response during CR, leading to increased eosinophil infiltration and anti-inflammatory macrophage polarization in fat of the CR animals. Genetic and pharmacological suppression of the LPS-TLR4 pathway or transplantation with Tlr4-/- bone-marrow-derived hematopoietic cells increases beige fat development and ameliorates diet-induced fatty liver, while Tlr4-/- or microbiota-depleted mice are resistant to further CR-stimulated metabolic alterations. These data reveal signals critical for our understanding of the microbiota-fat signaling axis during CR and provide potential new anti-obesity therapeutics.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Bactérias
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Restrição Calórica
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Trato Gastrointestinal
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Fígado Gorduroso
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Microbioma Gastrointestinal
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Tecido Adiposo Bege
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Lipídeo A
Limite:
Animals
Idioma:
En
Revista:
Cell Metab
Assunto da revista:
METABOLISMO
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Suíça