Lipid Metabolism Regulation by Hyperosmolarity in Renal Cells.

CASALI, CECILIA IRENE; WEBER, KAREN; EMANUEL MOREL GOMEZ; FERNANDEZ TOME, MARIA DEL CARMEN

Boston, MA

Congreso; Experimental Biology 2015; 2015

Lipid metabolism regulation by hyperosmolarity in renal cells Casali, Cecilia; Weber, K,, Morel Gomez, E,, Fernández, MC.. Biología Celular y Molecular, Facultad de Farmacia y Bioquímica, UBA. IQUIFIB-CONICET. Argentina. E-mail: ccasali@ffyb.uba.arPhysiologically, renal medullary cells are immersed in an unusual extracellular matrix that shows a high osmolarity and plays a major role in the urine concentrating system. To survive and work in such environment, cells have developed adaptive and protective mechanisms. Various works from our laboratory showed that the preservation of membrane structure helps to maintain cell architecture and viability. We showed that changes in environmental osmolarity regulate membrane phospholipid (PL) synthesis and turnover. PL de novo synthesis requires fatty acids which usually come from cellular storage in triglycerides (TG) molecules. The aim of the present work was to evaluate whether hyperosmolarity modulates lipid metabolism through the activation of the transcription factor sterol response element binding protein (SREBP). For this purpose, MDCK cells, derived from renal structures, were incubated in isosmolar and hyperosmolar media. Then, SREBP participation in TG synthesis and storage, and in the expression of the main TG biosynthetic enzymes, was evaluated. Results showed that hyperosmolarity increased TG storage and synthesis, and also the expression of fatty acid synthase (FAS), acetyl-CoA carboxylase and lipin-2 mRNA levels. Fatostatin (20 M), a SREBP inhibitor, blocked hyperosmolar-increased TG content and synthesis, and the expression of FAS enzyme. Fatostatin treatment also decreased the number of cells that survive to the treatment. These results suggest that hyperosmolarity activates SREBP which in turn modulates lipid synthesis. Thus, SREBP would play a key role in cell adaptation to osmotic changes by ensuring the substrates for PL synthesis that leads to membrane homeostasis.This work was supported by CONICET grant 0327 and PICT 2013-1132