title: Fueling the flame: bioenergy couples metabolism and inflammation.
abstract: We review the emerging concept that changes in cellular bioenergetics concomitantly reprogram inflammatory 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 organs. The initiating proinflammatory phase of inflammation is anabolic and requires glucose as the primary fuel, whereas the opposing adaptation phase is catabolic 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 inflammation and metabolism by chromatin and protein reprogramming. The AMP-AMPK/NAD(+)-SirT axis proceeds sequentially during acute systemic inflammation associated with sepsis but ceases during chronic inflammation associated with diabetes, obesity, and atherosclerosis. Rebalancing bioenergetics resolves inflammation. Manipulating cellular bioenergetics is identifying new ways to treat inflammatory and immune diseases.
authors.affiliation: Section of Molecular Medicine, Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA. tliu@wfubmc.edu
authors.forename: Tie Fu
authors.initials: TF
authors.lastname: Liu
authors.forename: Candice M
authors.initials: CM
authors.lastname: Brown
authors.forename: Mohamed
authors.initials: M
authors.lastname: El Gazzar
authors.forename: Linda
authors.initials: L
authors.lastname: McPhail
authors.forename: Patrick
authors.initials: P
authors.lastname: Millet
authors.forename: Anuradha
authors.initials: A
authors.lastname: Rao
authors.forename: Vidula T
authors.initials: VT
authors.lastname: Vachharajani
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Yoza
authors.forename: Charles E
authors.initials: CE
authors.lastname: McCall
mesh_terms: D000818:Animals; D004734:Energy Metabolism / Q000502:physiology*; D006801:Humans; D007249:Inflammation; D015398:Signal Transduction / Q000502:physiology*