The Warburg effect then and now: from cancer to inflammatory diseases

Bioessays. 2013 Nov;35(11):965-73. doi: 10.1002/bies.201300084. Epub 2013 Sep 20.

Abstract

Inflammatory immune cells, when activated, display much the same metabolic profile as a glycolytic tumor cell. This involves a shift in metabolism away from oxidative phosphorylation towards aerobic glycolysis, a phenomenon known as the Warburg effect. The result of this change in macrophages is to rapidly provide ATP and metabolic intermediates for the biosynthesis of immune and inflammatory proteins. In addition, a rise in certain tricarboxylic acid cycle intermediates occurs notably in citrate for lipid biosynthesis, and succinate, which activates the transcription factor Hypoxia-inducible factor. In this review we take a look at the emerging evidence for a role for the Warburg effect in the immune and inflammatory responses. The reprogramming of metabolic pathways in macrophages, dendritic cells, and T cells could have relevance in the pathogenesis of inflammatory and metabolic diseases and might provide novel therapeutic strategies.

Keywords: Hif-1α; PKM2; TLR; Warburg effect; glycolysis; inflammation; metabolism.

Publication types

  • Review

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Animals
  • Carrier Proteins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Citric Acid / metabolism
  • Citric Acid Cycle / physiology
  • Dendritic Cells / metabolism
  • Glycolysis / physiology*
  • Hexokinase / metabolism
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Immunity, Innate
  • Inflammation / immunology
  • Inflammation / pathology*
  • Lipopolysaccharides / metabolism
  • Macrophages / metabolism
  • Membrane Proteins / metabolism
  • Metabolic Networks and Pathways / physiology
  • Mitochondria / metabolism
  • Neoplasms / immunology
  • Neoplasms / pathology*
  • Oxidative Phosphorylation
  • Protein-Serine-Threonine Kinases / metabolism
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • Succinic Acid / metabolism
  • Thyroid Hormones / metabolism
  • Transcription Factors / metabolism

Substances

  • Carrier Proteins
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Lipopolysaccharides
  • Membrane Proteins
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • Thyroid Hormones
  • Transcription Factors
  • thyroid hormone-binding proteins
  • Citric Acid
  • Succinic Acid
  • Hexokinase
  • Protein-Serine-Threonine Kinases
  • AMP-Activated Protein Kinases