Effect of fatostatin on hyperosmolality-activated lipid metabolism in renal epithelial cells.

CASALI, CECILIA IRENE; WEBER KAREN; MESSINGER, DAIANA; PARRA, LEANDRO; . FERNÁNDEZ TOME, MARIA DEL CARMEN

Buenos Aires

Congreso; XLIX Reunión Anual de la Sociedad Argentina de Investigaciones Bioquímicas y Biología Molecular-SAIB; 2013

SAIB

In the renal cell line MDCK, we demonstrated that the increase in environmental osmolarity up-regulates phospholipid (PL) and triglycerides (TG) metabolism. The aim of the present work was to evaluate whether or not the increase in lipid metabolism requires the activation of the transcription factor sterol response element binding protein (SREBP). With this purpose, MDCK cells were incubated in isosmolar and hyperosmolar medium (containing 125 mM NaCl) alone or in the presence of different concentrations (10-25 M) of fatostatin (FATO), a SREBP inhibitor. To evaluate lipid synthesis 0.4 Ci 14C(U)-glycerol was added to the incubation medium 3 h before cell collection. After 24 h of treatment with NaCl, cells were collected, counted and lipid content and biosynthesis determined. FATO decreased the number of cells. Hypertonicity increased total PL and TG content by 60 and 100 %, respectively, unexpectedly FATO increased PL and TG accumulation. FATO (10, 15 and 20 M) decreased 14C-gly incorporation into DAG (by 60, 70 and 80 %) but not change on PL and TG synthesis was observed. These results suggest that hypertonicity would activate SREBP which in turn would modulate the up-regulation observed in lipid synthesis under hyperosmotic conditions.