Function of Glycerol-3-phosphate acyltransferases 2 and 3 in non-lipogenic tissues

GARCIA FABIANI, M.B.; QUIROGA, I.Y.; CATTANEO, E.R.; MONTANARO, M.A.; PELLON-MAISON, M.; GONZALEZ BARO, M.R.

Puerto Iguazu

Congreso; 56th International Conference on the Bioscience of Lipids; 2015

ICBL

Glycerol-3-phosphate acyltransferases (GPATs) catalyze thefirst and committed step in the cellular glycerolipid biosynthesispathway.  In mammals, 4 isoforms havebeen described differing in their cellular and tissue localization.   GPATs 1, 3 and 4 have been linked to de novosynthesis of TAG and PL in lipogenic tissues whereas the role of GPAT2 iscontroversial.  GPAT3 is the mayorisoform in adipose tissue and GPAT2 is expressed in testis and some cancercells.  Our aim is to determine GPAT2 and3 roles in non-lipogenic tissues.We studied the expression of GPAT3 inmonocyte-macrophage-foam-cell transition (a model of lipid accumulation duringatherogenesis) and in macrophage activation (a model of inflammation) byqRT-PCR in the murine macrophage RAW264.7 either differentiated into foam cellsby oxidized LDL (oxLDL) or activated by Kdo-Lipid A, and in the human THP-1monocyte cell line differentiated into macrophage by phorbol esters.  The treatment of macrophages with oxLDL andKdo increased lipid droplet area, as well as cellular TAG content.  GPAT3 expression increased 35-fold after 8 hof oxLDL and 6-fold after of Kdo exposure of macrophages, 6-fold after 12 h ofPMA activation of monocytes and correlated with GPAT enzymatic activity. Theseresults suggest that GPAT3 could be important in macrophage lipid accumulationduring activation-differentiation.We evaluated the expression of GPAT2 during the first waveof spermatogenesis and determined a peak at 15dpp regulated by DNA methylationand retinoic acid.  We then performed anin vivo lentivirus-mediated silencing of GPAT2 in mouse testis.  Histological and immunohistochemical analysisshowed both a strong post-meiotic arrest and a severe decrease in the number ofmature sperm cells in those tubules with diminished GPAT2 proteinexpression.  Our results show that GPAT2is important for the normal progress of spermatogenesis.