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

IGLESIAS GONZALEZ, P; CONDE, MELISA A.; SALVADOR, G; URANGA ROMINA

Parana

Congreso; LIV Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB), 5 al 8 de noviembre de 2018, Paraná, Entre Ríos, Argentina; 2018

SAIB

We have previously demonstrated that menadione-induced oxidative stress significantly diminishes adipogenesis and is able to dephosphorylateand inactivate phosphatidylinositol 3-kinase (PI3K)/Akt pathway in 3T3-L1 cells (SAIB 2017). To investigate this unexpected behavior of thisadipogenic key pathway against oxidative stress, we mimicked menadione effect by studying adipogenic differentiation in the presence ofLY294002, a well known PI3K inhibitor. In the absence of menadione, we found that PI3K inhibition drastically decreased adipogenesis. At amolecular level, the expression of peroxisome proliferator activated receptor gamma (PPAR gamma), the master regulator of adipogenesis, wasalso found to be decreased. To investigate if PI3K/Akt pathway was responsible of menadione-caused adipogenesis inhibition, we used insulin inthe 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 keypathway in the antiadipogenic effect of menadione on 3T3-L1 cells