Sirtuins Link Inflammation and Metabolism

Figure 2

Sirtuins and acute inflammation of sepsis: the extreme stress response of sepsis rapidly induces a systemic and potentially lethal hyperinflammatory state (red), which shifts within hours to a counterreactive hypoinflammation/adaptation phase (blue). NAD+ activation of sirtuins directs this switch. Mechanistically, nuclear SIRT1 levels briefly drop when homeostasis deviation initiates the glycolysis-dependent hyperinflammation, but within hours nuclear and mitochondrial sirtuin activation shifts glycolysis to fatty acid oxidation. This metabolic reprogramming globally represses immunity, affecting neutrophils, monocytes, dendritic cells, NK cells, and T lymphocytes. Resolution of acute inflammation and sepsis rebalances sirtuins and inflammation to restore homeostasis. Persistent elevation of sirtuins and hypoinflammation as a result lead to death (denoted by light blue area).