High-NaCl induces SREBP-mediated transcriptional regulation of triglycerides.

WEBER, K; CASALI, CI; MALVICINI, R; PARRA, L; ETCHEVERRY, T; FERNÁNDEZ-TOME, MC

Córdoba

Congreso; LII Reunión Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2016

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

Hypertonicity regulates phospholipid (PLs) and TAG synthesis. It is known that these metabolic pathways can be regulated by transcriptional activation of their biosynthetic enzymes. Several transcription factors may be involved in such a regulation but sterol response element binding protein (SREBP) is considered the master regulator of lipogenic genes. We showed that MDCK cells subjected to high NaCl induced changes in mRNA expression and cell distribution of SREBP isoforms. These changes were consistent with the increased levels of FLs and TAG in treated cells and with the fall in lipid synthesis after fatostatin treatment. However, we did not establish which isoform, SREBP1 (S1) and/or SREBP2 (S2), is responsible for the increased lipogenic activity. The present work was aimed to address this. Previous to the addition of hypertonic medium, MDCK cells were treated with S1-siRNA or S2-siRNA or both. After NaCl treatment lipid synthesis was studied. PLs and 1,2 DAG synthesis were not affected by any siRNA. In contrast, both 1,3 DAG and TAG synthesis were blocked. S1-siRNA decreased DAG and TAG synthesis by 33 and 46 %. S2-siRNA decreased DAG and TAG by 40 and 37%, respectively. Both siRNAs reduced synthesis by 55 %. So, SREBPs are needed to maintain TAG synthesis and its degradation to DAG but PLs synthesis remains constant indicating that SREBP-mediated transcriptional regulation is not involved.