Menadione modulates adipogenic differentiation by inhibition of PI3K/Akt pathway in 3T3-L1 cells

IGLESIAS GONZÁLEZ, PABLO A.; CONDE, MELISA A.; SALVADOR, GABRIELA A.; URANGA, ROMINA M.

Paraná

Congreso; LIV Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2018

We have previously demonstrated that menadione-induced oxidative stress significantly diminishes adipogenesis and is able to dephosphorylate and inactivate phosphatidylinositol 3-kinase (PI3K)/Akt pathway in 3T3-L1 cells (SAIB 2017). To investigate this unexpected behavior of this adipogenic key pathway against oxidative stress, we mimicked menadione effect by studying adipogenic differentiation in the presence of LY294002, a well known PI3K inhibitor. In the absence of menadione, we found that PI3K inhibition drastically decreased adipogenesis. At a molecular level, the expression of peroxisome proliferator activated receptor gamma (PPAR gamma), the master regulator of adipogenesis, was also found to be decreased. To investigate if PI3K/Akt pathway was responsible of menadione-caused adipogenesis inhibition, we used insulin in the presence of menadione as a PI3K gain-of-function strategy, both being present during the whole differentiation process. These experimentsshowed that insulin was sufficient to rescue PPAR gamma expression, without altering cell viability. These results show that PI3K/Akt is a key pathway in the antiadipogenic effect of menadione on 3T3-L1 cells.