CDK4 INHIBITION IMPAIRS BROWNING OF INGUINAL ADIPOSE TISSUE

PORTALES ANDREA; HARNICHAR EZEQUIEL; GAMBARO SABRINA ELIANA; GIOVAMBATTISTA , ANDRÉS; MIGUEL IGNACIO

Mar del Plata

Congreso; LXIII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC); 2018

SAIC

Browning of adipose tissue (AT) is the appearance of thermogenically competent adipocytes in white AT depots upon cold exposure. Here, we aimed to assess if browning is regulated by cyclin-dependent kinase 4 (CDK4) activity. To this end, CDK4 was inhibited with simultaneous browning stimulation. C57BL/6J male mice were gavaged CDK4 inhibitor (Palbociclib (PAL), 50mg/Kg) or vehicle for 10 days. At day 3, groups were subdivided: half remained at 22°C (PAL and CTR) and the others were housed at 4°C (PAL-C and CTR-C). Body weight and caloric intake were daily recorded. At day 10, mice were euthanized and inguinal AT (IAT) was collected. Besides, stroma vascular fraction of IAT from CTR and PAL groups was differentiated to adipocytes. At day 8 post-differentiation, a subgroup of CTR and PAL differentiated adipocytes was treated with Forskolin for thermogenesis stimulation (CTR-F and PAL-F). qPCR was used in all experiments for analysis of thermogenic markers (Ucp1, Pgc1a, Prdm16). Results showed no differences in body weight between groups, whereas cold induced a rise in caloric intake (CTR-C vs CTR and PAL-C vs PAL). In IAT, PAL reduced expression of Ucp1, Pgc1a and Prdm16 in both basal and browning stimulated conditions (p