CONICET | Buscador de Institutos y Recursos Humanos

Glycerol-3-phosphate acyltransferases (GPATs) catalyze the first and committed step in the cellular glycerolipid biosynthesis pathway. In mammals, 4 isoforms have been described differing in their cellular and tissue localization. GPATs 1, 3 and 4 have been linked to de novo synthesis of TAG and PL in lipogenic tissues whereas the role of GPAT2 is controversial. GPAT3 is the mayor isoform in adipose tissue and GPAT2 is expressed in testis and some cancer cells. Our aim is to determine GPAT2 and 3 roles in non-lipogenic tissues.We studied the expression of GPAT3 in monocyte-macrophage-foam-cell transition (a model of lipid accumulation during atherogenesis) and in macrophage activation (a model of inflammation) by qRT-PCR in the murine macrophage RAW264.7 either differentiated into foam cells by oxidized LDL (oxLDL) or activated by Kdo-Lipid A, and in the human THP-1 monocyte cell line differentiated into macrophage by phorbol esters. The treatment of macrophages with oxLDL and Kdo increased lipid droplet area, as well as cellular TAG content. GPAT3 expression increased 35-fold after 8 h of oxLDL and 6-fold after of Kdo exposure of macrophages, 6-fold after 12 h of PMA activation of monocytes and correlated with GPAT enzymatic activity. These results suggest that GPAT3 could be important in macrophage lipid accumulation during activation-differentiation.We evaluated the expression of GPAT2 during the first wave of spermatogenesis and determined a peak at 15dpp regulated by DNA methylation and retinoic acid. We then performed an in vivo lentivirus-mediated silencing of GPAT2 in mouse testis. Histological and immunohistochemical analysis showed both a strong post-meiotic arrest and a severe decrease in the number of mature sperm cells in those tubules with diminished GPAT2 protein expression. Our results show that GPAT2 is important for the normal progress of spermatogenesis