INHIBITION OF CYCLIN-DEPENDENT KINASE 4 (CDK4) ACTIVITY IN ADIPOCYTES ENHANCES THEIR THERMOGENIC PROGRAM

PORTALES ANDREA; MIGUEL IGNACIO; GIOVAMBATTISTA , ANDRÉS

Mar del Plata

Congreso; LXI REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA; 2016

SAIC

Beige adipocytes are thermogenically competent cellsthat develop in white adipose tissue (WAT) depots in responseto b-adrenergic receptors stimulation. Two generalmechanisms are accepted for beige adipocytes generation:de novo adipogenesis from beige precursor cells,and transdifferentiation from white adipocytes. In previousstudies we found that inhibition of cyclin-dependent kinase4 (CDK4) activity in stromal vascular fraction cells (SVF)from WAT led to an increase in beige adipocyte markers.Here we wanted to assess if the inhibition of CDK4 activityis involved in white to beige adipocyte transdifferentiation.To this aim, SVF cells from the epididimal depot ofC$L/, mice Yere isolated n, cultured to confluenceand differentiated with an adipogenic cocktail. Onday 8 post-differentiation, cells were treated or not with aninhibitor of CDK4 (Palbociclib (PAL) 1µM; CTR) for 48hs.In additional experiments, after the inhibition period, CTRand PAL cells were treated with Forskolin (FSK) 10µM for4hs in order to activate the thermogenic program (CTRFand PAL-F). Finally, on day 10 cells were processedfor total 40A extraction and 4Tq2C4 quantification ofthermogenic (Ucp1, Prdm16), beige (Cd137) and generaladipogenic (adiponectin) markers. Results showed thatinhibition of C&- in adipocytes resulted in a significantincrease in Ucp1 and Prdm16 mRNA levels in the PALgroup compared to the CTR (p