THE PHOSPHATIDYLCHOLINE TRANSFER PROTEIN STARD7 PARTICIPATES IN CELLULAR LIPID METABOLISM

FLORES MARTIN, JESICA B.; ROJAS, MARÍA L.; NARDI, SOFIA; KOURDOVA LUCILLE; RACCA, ANA C.; PANZETTA-DUTARI, GRACIELA M.; GENTI-RAIMONDI, SUSANA

Mar del Plata

Congreso; Reunión Conjunta de Biociencias SAIC-SAI-SAFIS; 2022

SAIC-SAI-SAFIS

The increased prevalence of metabolic diseases has become ahealth problem that decreases life expectancy. Reports indicate thata diet deficient in methionine/choline or decreased phosphatidylcholine(PC) synthesis induces hepatic steatosis, at least in part due toreduced VLDL secretion. StarD7 is a PC transfer protein that belongsto the START superfamily, which are involved in metabolism,transport and intracellular signaling of lipids. In the present studywe explored the participation of StarD7 in cellular lipid metabolism.Stable HepG2 cell lines silenced of StarD7 (shD7), and its control(shC) were generated. Data from qPCR demonstrated that StarD7silencing lead to a significant increase of the mRNA levels of ATP-citrateLyase (ACLY) and stearoyl-CoA desaturase (SCD) enzymesresponsible for fatty acid synthesis. Also, lipid droplets stained bythe fluorescent dye BODIPY (493/503) confirmed an increase ofthe neutral lipid storage in shD7 cells vs shC showed by microscopy.In addition to the CDP-choline pathway for PC synthesis,the liver also uses an additional pathway catalyzed by the enzymephosphatidylethanolamine N-methyltransferase (PEMT) enzyme.Western bot assays carried out from HepG2 cells stably depletedof PEMT showed higher StarD7 expression compared to shC.Also, the addition of PC to the culture medium restores the levelsof StarD7. Additionally, shPEMT cells exposed to a lipotoxic environment(200 μmol/L C16:0 palmitic acid or C18:1 oleic acid) for 24hours expressed higher StarD7 levels than control, suggesting theinvolvement of StarD7 in the maintenance of lipid homeostasis. Collectively,these results highlight the role of StarD7 in the regulationof lipid biosynthesis. We consider it is essential to study the mechanismsthat regulate lipid metabolism at cellular level to understandbiological processes and develop effective therapies in patients withmetabolic diseases.