Modulatory effect of testosterone on the thermogenic activity of beige adipocytes from retroperitoneal adipose tissue.

SPINEDI E; REY MA; ZUBIRIA G; GIOVAMBATTISTA A

Mar del Plata

Congreso; LXI Reunion de la Sociedad Argentina de Investigacion Clinica (SAIC).; 2016

It is well known thatandrogens modulate adipose tissue (AT) distribution and function. We earliershowed the effect of the lack of testosterone (T) on retroperitoneal AT (RPAT)function from orchidectomized rats and the inhibitory action of T on theadipogenic potential of adipocyte precursor cells (APCs) in vitro. We now studied the effect of T, in vivo and in vitro, onthe thermogenic activity of beige adipocytes from RPAT. For this aim, RPAT padswere dissected from adult male control (CTR), pre-pubertally orchidectomized(ODX) and pair-fed control (CTR-PF) rats. Pads were processed for histologyanalysis and UCP-1 quantification (RT-PCR). In addition, APCs from adult malerats were isolated and cultured up to confluence, then cells were induced todifferentiate (4 days) with a pro-browning cocktail in the absence or presenceof 0.1 µM T (basal (B) or T, respectively); thereafter cells remained inculture medium without or with T. On differentiation day 8, we added 10 µMforskolin (FSK) for 4 hs to a subset of B or T cells: B without FSK (B-B), Bwith FSK (B-FSK), T without FSK (T-B), T with FSK (T-FSK). Cells were thenprocessed to quantify UCP-1. We found that T decreased UCP-1 expression in in vitro differentiated adipocytes(p<0.01, T-B vs B-B). As expected, FSK increases UCP-1 gene expression inRPAT adipocytes (B-B vs B-FSK and T-B vs T-FSK, p<0.01). However,FSK-induced UCP-1 expression was low in T-treated cells (p<0.01, T-FSK vsB-FSK). On the other hand, UCP-1 gene expression in RPAT from ODX rats was high(p<0.05, ODX vs CTR and CTR-PF). Histological analysis indicated thepresence of small adipocytes in RPAT from ODX rats (p<0.05, ODX vs CTR andCTR-PF) and the of appearance multivacuolar, beige-like adipocytes. We concludethat T could be modulating the thermogenic program of beige adipocytes fromRPAT by regulating UCP-1 gene expression. (PIP 0198; FPREDM052015)