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Immune response to pathogens is energetically expensive to the host, however, the cellular source of energy to fuel immune response remains unknown. In this study, we show that C. elegans exposed to pathogenic Gram-positive and Gram-negative bacteria, or yeast rapidly utilizes lipid droplets, the major energy reserve. Nematode's response to pathogenic bacterium Enterococcus faecalis entails metabolic rewiring for upregulation of several genes involved in lipid utilization and downregulation of lipid synthesis genes. Acyl-CoA synthetase,