SREBP‐1a, lipid metabolism and the innate immune response

Abstract

Recent reports suggest a connection between primary lipid metabolic pathways and other physiologic processes that are influenced by cellular lipid levels. The sterol regulatory element binding protein (SREBP) transcription factors have been demonstrated to be required for these connections through coordinating the expression of genes required for key physiologic processes as well as genes encoding key enzymes of intermediary lipid metabolism. Expression levels for the three individual mammalian SREBPs vary dramatically across different tissues. The SREBP‐1a isoform is abundantly expressed in macrophages and our recent studies showed that it couples lipid synthesis to the proinflammatory branch of the innate immune response. We have extended these observations to provide evidence that SREBP‐1a also regulates two additional branches of the macrophage innate defense response against pathogen engagement including the pro‐survival antiapoptotic response following exposure to bacterial pore‐forming toxins as well as phagocytosis. These studies will be integrated into a model for how SREBPs have evolved to more broadly couple lipid synthetic pathways with the host‐environment interface.