Key result
LPS stimulation significantly increased oleate oxidation and deposition as cellular lipid at 48 hours, but abolished both oxidation and storage of VLDL-TAG in rat macrophages.
During sepsis/endotoxemia, VLDL utilization by macrophages is limited and directed away from oxidation, suggesting it supplies cellular lipid rather than acting as a respiratory fuel.
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Should not yet change sepsis care; hypothesis-generating for VLDL redirection in macrophage lipid metabolism.
BACKGROUND/AIMS: Plasma very-low-density lipoprotein (VLDL) concentrations are increased during sepsis/endotoxaemia and VLDL may be substrates for the activated immune system. Lipid substrate utilisation by quiescent and activated macrophages was therefore examined. METHODS: Rat R2 macrophages were incubated with oleate or rat VLDL, with or without lipopolysaccharide (LPS) stimulation. The metabolic fate of the lipids was examined. RESULTS: Macrophages utilised both oleate and (control) VLDL-triacylglycerol (TAG) to a similar extent. Most was deposited as cellular lipid; about 10% of oleate was oxidised compared to 25% of cVLDL-TAG. LPS significantly increased oleate oxidation and its deposition as cellular lipid (mostly as TAG) at 48hrs but abolished both oxidation and storage of VLDL-TAG. VLDL produced during endotoxaemia (eVLDL) was assimilated by the unstimulated macrophage to a greater extent than oleate or cVLDL-TAG and selectively stored as cellular lipids (no oxidation); LPS decreased eVLDL utilisation. VLDL-TAG utilisation was decreased by the lipoprotein lipase (LPL) inhibitor terahydrolipstatin. LPL activity was greater in oleate than in VLDL incubations, but was increased by incubation with eVLDL. LPS had no effect (oleate, cVLDL) or increased (eVLDL) LPL activity. CONCLUSION: VLDL represented an efficient substrate for the macrophage. However under conditions of sepsis/endotoxaemia eVLDL utilisation was limited and directed away from oxidation, suggesting that the increased plasma TAG (eVLDL) concentrations resulting from sepsis is not a respiratory fuel for the macrophage but may supply cellular lipid.
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Hauton et al. (2002) studied Sepsis/endotoxaemia. Lipopolysaccharide (LPS) stimulation vs. Unstimulated macrophages was evaluated on Lipid substrate utilisation (oxidation and deposition as cellular lipid). LPS stimulation significantly increased oleate oxidation and deposition as cellular lipid at 48 hours, but abolished both oxidation and storage of VLDL-TAG in rat macrophages.
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