| First Author | Fabbiano S | Year | 2018 |
| Journal | Cell Metab | Volume | 28 |
| Issue | 6 | Pages | 907-921.e7 |
| PubMed ID | 30174308 | Mgi Jnum | J:269123 |
| Mgi Id | MGI:6270087 | Doi | 10.1016/j.cmet.2018.08.005 |
| Citation | Fabbiano S, et al. (2018) Functional Gut Microbiota Remodeling Contributes to the Caloric Restriction-Induced Metabolic Improvements. Cell Metab 28(6):907-921.e7 |
| abstractText | 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. |
