Active Ingredients: Orlistat
Rice et al. This suggests requirement of glucose metabolism for the early phase of high and intense ROS production, while both fatty acid metabolism and mitochondrial function facilitated prolonged H 2 O 2 production during the late phase.
Various soluble chemotaxins accelerate the transmembrane glucose uptake without affecting stored endogenous glycogen 73. Neutrophil Extracellular Traps NETs Neutrophils release chromatin traps along with antimicrobial granular contents through NETosis to kill and prevent the dissemination of pathogens 6.
NETosis is also energy driven catabolic process that requires inter-mixing of cytoplasmic granules with decondensed nuclear chromatin, and expulsion of filamentous traps 6, 21.
Recent studies are focusing on finding the metabolic requirement of NETosis 20, 21, which suggest its dependent on glucose but not on glutamine 20. Moreover, ROS, a known driver of NETosis was less dependent on glucose during the initial phase of chromatin decondensation 20.
Rodriguez-Espinosa et al. Subsequent study conducted by Azevedo et al. It is also important to mention that due to short life of neutrophils most of metabolic studies are conducted using pharmacological agents, which also have non-specific effects.
Until recently, it has been well-accepted that under anaerobic conditions glucose produces lactate as metabolic waste. Recently, two independent breakthrough studies using 13 C-lactate tracing identified that lactate can be converted to pyruvate and fuel metabolism through TCA cycle 78, 79.
Lactate can be converted back to glucose in the liver through Cori cycle 78, 79. Neutrophils are commonly present in hypoxic and inflammatory sites that are often enriched with lactate, but role of lactate in neutrophil function is relatively less explored.
In light of the recent paradigm shift in role of lactate in metabolism, lactate might play a unique role in NETosis.
Consist to this, Alarcon et al. Significant changes in the lactate level during diverse metabolic and inflammatory diseases, like diabetes, sepsis etc, might modulate neutrophil responses and NETosis.
NETosis has been linked with both physiological and pathological conditions 3, thus necessitating a proper understanding of the metabolic requirements for improved understanding and for developing future therapeutic interventions.