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Raulien N, Friedrich K, Strobel S, et al. Fatty Acid Oxidation Compensates for Lipopolysaccharide-Induced Warburg Effect in Glucose-Deprived Monocytes. Front Immunol. 2017;8:609doi: 10.3389/fimmu.2017.00609.
Raulien, N., Friedrich, K., Strobel, S., Rubner, S., Baumann, S., von Bergen, M., Körner, A., Krueger, M., Rossol, M., & Wagner, U. (2017). Fatty Acid Oxidation Compensates for Lipopolysaccharide-Induced Warburg Effect in Glucose-Deprived Monocytes. Frontiers in immunology, 8609. https://doi.org/10.3389/fimmu.2017.00609
Raulien, Nora, et al. "Fatty Acid Oxidation Compensates for Lipopolysaccharide-Induced Warburg Effect in Glucose-Deprived Monocytes." Frontiers in immunology vol. 8 (2017): 609. doi: https://doi.org/10.3389/fimmu.2017.00609
Raulien N, Friedrich K, Strobel S, Rubner S, Baumann S, von Bergen M, Körner A, Krueger M, Rossol M, Wagner U. Fatty Acid Oxidation Compensates for Lipopolysaccharide-Induced Warburg Effect in Glucose-Deprived Monocytes. Front Immunol. 2017 May 29;8:609. doi: 10.3389/fimmu.2017.00609. eCollection 2017. PMID: 28611773; PMCID: PMC5447039.
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Front Immunol. 2017 May 29;8:609. doi: 10.3389/fimmu.2017.00609. eCollection 2017.

Fatty Acid Oxidation Compensates for Lipopolysaccharide-Induced Warburg Effect in Glucose-Deprived Monocytes.

Frontiers in immunology

Nora Raulien, Kathleen Friedrich, Sarah Strobel, Stefan Rubner, Sven Baumann, Martin von Bergen, Antje Körner, Martin Krueger, Manuela Rossol, Ulf Wagner

Affiliations

  1. Division of Rheumatology, Department of Internal Medicine, University of Leipzig, Leipzig, Germany.
  2. Department of Molecular Systems Biology, Helmholtz Centre for Environmental Research - UFZ, Leipzig, Germany.
  3. Faculty of Biosciences, Pharmacy and Psychology, Institute of Pharmacy, University of Leipzig, Leipzig, Germany.
  4. Faculty of Biosciences, Pharmacy and Psychology, Institute of Biochemistry, University of Leipzig, Leipzig, Germany.
  5. Hospital for Children and Adolescents, Department of Women and Child Health, University Hospitals, University of Leipzig, Leipzig, Germany.
  6. Institute of Anatomy, University of Leipzig, Leipzig, Germany.

PMID: 28611773 PMCID: PMC5447039 DOI: 10.3389/fimmu.2017.00609

Abstract

Monocytes enter sites of microbial or sterile inflammation as the first line of defense of the immune system and initiate pro-inflammatory effector mechanisms. We show that activation with bacterial lipopolysaccharide (LPS) induces them to undergo a metabolic shift toward aerobic glycolysis, similar to the Warburg effect observed in cancer cells. At sites of inflammation, however, glucose concentrations are often drastically decreased, which prompted us to study monocyte function under conditions of glucose deprivation and abrogated Warburg effect. Experiments using the Seahorse Extracellular Flux Analyzer revealed that limited glucose supply shifts monocyte metabolism toward oxidative phosphorylation, fueled largely by fatty acid oxidation at the expense of lipid droplets. While this metabolic state appears to provide sufficient energy to sustain functional properties like cytokine secretion, migration, and phagocytosis, it cannot prevent a rise in the AMP/ATP ratio and a decreased respiratory burst. The molecular trigger mediating the metabolic shift and the functional consequences is activation of AMP-activated protein kinase (AMPK). Taken together, our results indicate that monocytes are sufficiently metabolically flexible to perform pro-inflammatory functions at sites of inflammation despite glucose deprivation and inhibition of the LPS-induced Warburg effect. AMPK seems to play a pivotal role in orchestrating these processes during glucose deprivation in monocytes.

Keywords: Warburg effect; fatty acid oxidation; glucose deprivation; inflammation; monocytes

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