Role of GPA3/4 in glycerolipid synthesis, phagocytosis and cytokine release in activated macrophages

PELLON-MAISON, M.; COLEMAN, R.A.; QUIROGA, I.Y.; GONZALEZ BARO, M.R.

Cordoba

Congreso; LII Reunión Anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular (SAIB); 2016

SAIB

Glycerol-3-phosphate acyltransferase (GPAT) regulates de novo glycerolipid synthesis. GPATactivity is up-regulated during macrophage activation, when PL and TAG accumulationin lipid droplets (LDs) is increased. We studied the role of GPAT3 and GPAT4 duringmacrophage activation in a shGpat3 macrophagecell line and Gpat3-/-and Gpat4-/- mice BoneMarrow Derived Macrophages (BMDM). Activated shGpat3 cells accumulate 40, 30 and 65% less LDs, TAG and PL thancontrol cells;  Gpat3-/- BMDM store 25, 50, and 78% less LDs, TAG and PL;and the accumulation in activated Gpat4-/-BMDM is 42, 54 and 58% lower compared with the wt. We analyzed the incorporation of [14C]-Acetate and [14C]-Oleicacid (OA) into lipids in activated shGpat3cells, Gpat3-/- and Gpat4-/- BMDM; theincorporation of both substrates decreased in the absence of GPAT3/4 and while GPAT3participates in PL and TAG synthesis, GPAT4 is involved mostly in TAGsynthesis. To investigate the physiological effect of impaired lipid synthesis,we analyzed the phagocytic capacity of shGpat3cells, Gpat3-/- and Gpat4-/- BMDM and itwas 45, 22 and 31% lower than in the activated controls. We found that theexpression and cytokine release during macrophage activation in these cells wasalso altered. Taken together, these results prove that GPAT3 and 4 contributeto the increase in total glycerolipid content, phagocytosis and cytokineproduction during macrophage activation.