Fueling the flame: bioenergy couples metabolism and inflammation

We review the emerging concept that changes in cellu-lar bioenergetics concomitantly reprogram inflamma-tory and metabolic responses. The molecular pathways of this integrative process modify innate and adaptive immune reactions associated with inflammation, as well as influencing the physiology of adjacent tissue and or-gans. The initiating proinflammatory phase of inflamma-tion is anabolic and requires glucose as the primary fuel, whereas the opposing adaptation phase is cata-bolic and requires fatty acid oxidation. The fuel switch to fatty acid oxidation depends on the sensing of AMP and NAD by AMPK and the SirT family of deacetylases (e.g., SirT1,-6, and-3), respectively, which couple in-flammation and metabolism by chromatin and protein reprogramming. The AMP-AMPK/NAD-SirT axis pro-ceeds sequentially during acute systemic inflammation associated with sepsis but ceases during chronic in-flammation associated with diabetes, obesity, and ath-erosclerosis. Rebalancing bioenergetics resolves in-flammation. Manipulating cellular bioenergetics is iden-tifying new ways to treat inflammatory and immune diseases. J. Leukoc. Biol. 92: 000–000; 2012