INIBIOLP   05426
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE LA PLATA "PROF. DR. RODOLFO R. BRENNER"
Unidad Ejecutora - UE
artículos
Título:
Glycerol-3-phosphate acyltransferases 3 and 4 direct glycerolipid synthesis and affect functionality in activated macrophages
Autor/es:
QUIROGA, I.Y.; COLEMAN, R.A.; PELLON-MAISON, M.; PELLON-MAISON, M.; GONZALEZ BARO, M.R.; GONZALEZ BARO, M.R.; SUCHANEK, A.L.; SUCHANEK, A.L.; QUIROGA, I.Y.; COLEMAN, R.A.
Revista:
BIOCHEMICAL JOURNAL
Editorial:
PORTLAND PRESS LTD
Referencias:
Lugar: Londres; Año: 2019 vol. 476 p. 85 - 99
ISSN:
0264-6021
Resumen:
Macrophage classical M1 activation via TLR4 triggers a variety of responses to achievethe elimination of foreign pathogens. During this process, there is also an increase inlipid droplets which contain large quantities of triacylglycerol (TAG) and phospholipid(PL). The functional consequences of this increment in lipid mass are poorlyunderstood. Here we studied the contribution of glycerolipid synthesis to lipidaccumulation, focusing specifically on the first and rate-limiting enzyme of thepathway: glycerol-3-phosphate acyltransferase (GPAT). Using bone marrow derivedmacrophages (BMDM) treated with Kdo2-lipid A (KLA), we showed that glycerolipidsynthesis is induced during macrophage activation. GPAT4 protein level andGPAT3/GPAT4 enzymatic activity increase during this process, and these two isoformswere required for the accumulation of cell TAG and PL. The phagocytic capacity ofGpat3-/- and Gpat4-/- BMDM was impaired. Additionally, inhibiting fatty acid β-oxidation reduced phagocytosis only partially, suggesting that lipid accumulation is notnecessary for the energy requirements for phagocytosis. Finally, Gpat4-/- BMDMexpressed and released more pro-inflammatory cytokines and chemokines aftermacrophage activation, suggesting a role for GPAT4 in suppressing inflammatoryresponses. Together these results provide evidence that glycerolipid synthesis directedby GPAT4 is important for the attenuation of the inflammatory response in activatedmacrophages.