Fatty Acid and Triacylglycerol Utilisation by Perfused Rat Spleen: Differential Metabolic Fate and the Effect of Endotoxin

Abstract

Background/Aims: The spleen uses significant amounts of non-esterified fatty acid (NEFA) and chylomicron (CM)-derived triacylglycerol (TAG); however, its utilisation of very-low-density lipoprotein triacylglycerol (VLDL-TAG), and the effect of endotoxin on lipid assimilation and fate are unknown. This study aims to define spleen utilisation of esterified and non-esterified fatty acid in quiescent and endotoxin-stimulated states.Methods: Rat spleens were perfused for 2h with glucose (11mM) and either NEFA (oleate; 0.4mM fatty acid), rat CM (0.4mM TAG), or rat VLDL (0.4mM TAG). Lipid oxidation and tissue lipid deposition were measured.Results: Total utilisation of oleate and VLDL-TAG were not significantly different. Utilisation of CM was 2-3 fold greater; however oxidation of CM-TAG (5.5nmols FA/min/gram spleen) was not significantly different from either NEFA or VLDL-TAG. More TAG (CM and VLDL) was deposited as tissue lipid compared to oxidation than NEFA; the pattern of intracellular lipid accumulation of TAG and NEFA also differed. Endotoxin (LPS) did not affect the proportion of lipid oxidised and accumulated or on TAG tissue lipid distribution but it increased the proportion of oleate recovered as tissue TAG and cholesterol ester. Perfusion with CM-TAG significantly decreased heparin-releasable lipoprotein lipase (LPL) activity compared with oleate or VLDL-perfused spleens. LPS increased LPL activity 5-fold in oleate-perfused spleens, but had no effect on VLDL-perfused spleens.Conclusion: VLDL-TAG is utilised by spleen to a similar extent as NEFA, but its pattern of metabolic fate resembles that of CM-TAG. Endotoxin affects the pattern of NEFA deposition in tissue lipids but has no significant effect on VLDL utilisation by the spleen.