Fueling the flame: bioenergy couples metabolism and inflammation
Open Access
- 9 May 2012
- journal article
- review article
- Published by Oxford University Press (OUP) in Journal of Leukocyte Biology
- Vol. 92 (3), 499-507
- https://doi.org/10.1189/jlb.0212078
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.Keywords
Funding Information
- U.S. National Institutes of Health (AI-065791)
- (C.E.M.) (AI-079144)
- (V.T.V.) (GM086470, MO-1RR 007,122)
This publication has 86 references indexed in Scilit:
- T Cell Myc-tabolismImmunity, 2011
- Facultative heterochromatin formation at the IL-1 beta promoter in LPS tolerance and sepsisCytokine, 2010
- Cellular Metabolic Stress: Considering How Cells Respond to Nutrient ExcessMolecular Cell, 2010
- Hepatic-Specific Disruption of SIRT6 in Mice Results in Fatty Liver Formation Due to Enhanced Glycolysis and Triglyceride SynthesisCell Metabolism, 2010
- The Histone Deacetylase Sirt6 Regulates Glucose Homeostasis via Hif1αCell, 2010
- SIRT6 Links Histone H3 Lysine 9 Deacetylation to NF-κB-Dependent Gene Expression and Organismal Life SpanCell, 2009
- Metabolic adaptations through the PGC‐1α and SIRT1 pathwaysFEBS Letters, 2007
- Selective degradation of mitochondria by mitophagyArchives of Biochemistry and Biophysics, 2007
- Nampt/PBEF/Visfatin: A regulator of mammalian health and longevity?Experimental Gerontology, 2006
- Oxidative metabolism and PGC-1β attenuate macrophage-mediated inflammationCell Metabolism, 2006