Details zur Publikation

Referenztyp Zeitschriften
DOI / URL Link
Titel (primär) Fatty acid oxidation compensates for lipopolysaccharide-induced Warburg effect in glucose-deprived monocytes
Autor Raulien, N.; Friedrich, K.; Strobel, S.; Rubner, S.; Baumann, S.; von Bergen, M.; Körner, A.; Krueger, M.; Rossol, M.; Wagner, U.;
Journal / Serie Frontiers in Immunology
Erscheinungsjahr 2017
Department MOLSYB;
Band/Volume 8
Sprache englisch;
POF III (gesamt) F11;
Keywords monocytes, Warburg effect, fatty acid oxidation, glucose deprivation, inflammation
UFZ Querschnittsthemen RU3;
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.
ID 18911
dauerhafte UFZ-Verlinkung
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
Front. Immunol. 8 , art. 609