In vivo and in vitro inhibitory effect of Dexamethasone on the thermogenic process of beige adipocytes

GIORDANO AP; ZUBIRIA G; GAMBARO SE; SPINEDI, E; GIOVAMBATTISTA A

CABA

Congreso; LXIII Reunión Anual SAIC; 2018

SAIC

Glucocorticoids(GCs) modulate white and brown adipose tissue (AT) biology and function; however,GCs effect on beige adipocytes activation remains unknown. We studied dexamethasone(DXM) effects on the thermogenic activity of beige adipocytes from RetroperitonealAT (RPAT). Male rats were divided into four groups: control (CTR) and DXMinjected (sc 0,03mg/Kg/d for 7 days, DXM) and housed at room temperature, andCTR and DXM housed under cold stimulus (4°C for 7 days, CTR-C and DXM-C,respectively). RPAT pads were dissected, weighted and processed for UCP-1 andPGC1⍺ quantification(RT-PCR). Both, DXM and cold exposure decreased RPAT mass/100 gr body weight(P<0.05). RPAT from DXM-C showed reduced levels of UCP-1 (p<0.01, vs CTR-C)and a tendency toward lower levels of PGC1⍺ gene expression. We alsostudied the effect of DXM in vitro onadipocyte precursor cells. Stromal vascular fraction cells were isolated fromRPAT from control male rats and cultured up to confluence. Cells were then incubatedor not with 0,25µM DXM for 48hs (DXM and CTR cells, respectively). Thereafter,cells were induced to differentiate with a pro-beige cocktail. On day 8 after differentiation,a subset of CTR and DXM cells were incubated in basal condition or with forskolin(10µM, FSK) for 4hs (CTR-FSK and DXM-FSK, respectively). Cells were thenprocessed to quantify UCP-1 and PGC1⍺ mRNAs. We found that DXM decreased UCP-1 expression in FSK stimulated adipocytes (p<0.0001, vs.CTR-FSK). Additionally, and following a similar protocol, we evaluated DXMeffect on trans-differentiation, by incubating or not with 0,25µM DXM the last48hs of culture. Again, we found that DXM decreased UCP-1 mRNA levels in DXM-FSKadipocytes (p<0.0001, vs. CTR-FSK). Overall, DXM inhibited the thermogenicprogram in RPAT beige adipocytes, in vivoand in vitro after cold and FSKstimulation, respectively, by regulating UCP-1 gene expression.(PICT2015-2352)