Fatty Acid Oxidation Compensates for Lipopolysaccharide-Induced Warburg Effect in
Glucose-Deprived Monocytes
#MMPMID28611773
Raulien N
; Friedrich K
; Strobel S
; Rubner S
; Baumann S
; von Bergen M
; Körner A
; Krueger M
; Rossol M
; Wagner U
Front Immunol
2017[]; 8
(?): 609
PMID28611773
show ga
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.
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