MCAM knockdown inhibits PPARγ expression in the late stages of 3T3-L1 fibroblasts differentiation to adipocytes

GABRIELLI, M; MARTINI, CN; VILA, MC

Ciudad de Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias - LXII Reunión Científica Anual de SAIC; 2017

Sociedad Argentina de Investigación Clínica

Obesity is a chronic diseasecharacterized by an excessive expansion of the adipose tissue which is associatedwith an increase in the number and size of adipocytes. Therefore, the knowledgeon the development and function of the adipose tissue may help to design newapproaches for the treatment of this disease. We have previously observed thatthe expression of Melanoma Cell Adhesion Molecule (MCAM), a transmembraneprotein of the immunoglobulin superfamily, increases during 3T3-L1 fibroblastsdifferentiation to adipocytes, subsequent to the activation of the masterregulator of adipogenesis, PPARγ, and this increase is maintained in the matureadipocytes. On the other hand, we have also found that shRNA mediated MCAMdownregulation impaired 3T3-L1 cells differentiation and induction of PPARγ aswell as expression of genes activated by PPARγ. To further evaluate the effectsof knocking down MCAM expression, we investigated the events that precede andare necessary for early PPARγ activation such as C/EBPβ induction, β-catenindownregulation and ERK activation. We found that these early events of thedifferentiation process were not affected in the MCAM knockdown cells. Inkeeping with this, the early increase in PPARγ mRNA observed 24 h afterinduction of differentiation and that precedes MCAM induction, was not alteredin the knockdown cells. However, PPARγ expression was inhibited after day 3 ofdifferentiation in these cells, when a positive feedback loop has beendescribed to be necessary to maintain PPARγ upregulation. In conclusion, ourfindings suggest that MCAM is a gene upregulated and necessary to maintainPPARγ induction in the late but not in the early stages of 3T3-L1 fibroblastsadipogenesis.