Fueling the flame: bioenergy couples metabolism and inflammation

Journal of Leukocyte Biology

Vidula T. Vachharajani–⁵  Charles E. McCall³  Linda McPhail⁴  Tie Fu Liu⁶  Barbara K. Yoza, and¹  Candice M. Brown⁶  Mohamed El Gazzar²  Patrick Millet⁶  Anuradha Rao⁶ 

[1] Section of Molecular Medicine, Department of Internal Medicine, Division of Surgical Sciences, and  Translational Science Institute, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA;Department of Internal Medicine, East Tennessee State University College of Medicine, Johnson City, Tennessee, USA  Translational Science Institute, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA;Section of Molecular Medicine, Department of Internal Medicine, Department of Internal Medicine, East Tennessee State University College of Medicine, Johnson City, Tennessee, USA  Translational Science Institute, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA;Departments of Biochemistry and  Translational Science Institute, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA;–Anesthesiology,  Translational Science Institute, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA;Section of Molecular Medicine, Department of Internal Medicine,  Translational Science Institute, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA;

关键词: AMP;    epigenetics;    fatty acid oxidation;    glycolysis;    HIF-1α;    NAD⁺;    Nampt;    obesity;    PGC-1;    sepsis;   

DOI  :  10.1189/jlb.0212078

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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.

【 授权许可】

Unknown