Functional Gut Microbiota Remodeling Contributes to the Caloric Restriction-Induced Metabolic Improvements
DOI: 10.1016/j.cmet.2018.08.005
Abstract & Authors 展开
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.
First Authors:
Salvatore Fabbiano
Correspondence:
Mirko Trajkovski
All Authors:
Salvatore Fabbiano,Nicolas Suárez-Zamorano,Claire Chevalier,Vladimir Lazarević,Silas Kieser,Dorothée Rigo,Stefano Leo,Christelle Veyrat-Durebex,Nadia Gaïa,Marcello Maresca,Doron Merkler,Mercedes Gomez de Agüero,Andrew Macpherson,Jacques Schrenzel,Mirko Trajkovski
2018-08-30Article
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