lipid-a and Fatty-Liver

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

Topics: Adipose Tissue, Beige; Animals; Bacterial Proteins; Caloric Restriction; Eosinophils; Fatty Liver; Gastrointestinal Microbiome; Gastrointestinal Tract; Lipid A; Macrophages; Male; Mice; Mice, Inbred C57BL; Toll-Like Receptor 4