Effects of Prepubertal Castration on White Adipose Tissue Thermogenesis

MIGUEL I; ALZAMENDI A; HARNICHAR E; GIORDANO A; SPINEDI E; GIOVAMBATTISTA A

Congreso; LXVI Reunión Anual Sociedad Argentina de Investigación Clínica; 2021

Sociedad Argentina de Investigación Clínica

Beige adipocytes dissipate energy as heat through the action of uncoupling protein-1 (UCP1). Cold exposure or β3 adrenergic agonist treatment stimulates beige adipocyte generation. Our aim was to study the effect of prepubertal ovariectomy (OVX) on Retroperitoneal Adipose Tissue (RPAT) pad thermogenesis using both in vivo and in vitro paradigms. On age 27 days, rats were randomly split into two groups, sham-ovariectomized (SHX) and OVX-pair fed (OVX-PF). On age 60-day old, one half of rats were kept at 4°C (C) during 7 days, while the other half was housed at room temperature (RT). Food intake and body weight (BW) were daily registered throughout these treatments. At sacrifice, RPAT pads were excised and weighed for the analyses of UCP-1, Pgc-1α, β3AR and DIO-2 gene expressions. Isolated adipocyte precursor cells (APCs), from both groups, were induced to differentiate and examined 6 days after 10 µM forskolin (FSK) addition or not. Later on, APCs from SHX RT animals were cultured in either basal conditions (B, medium alone) or in medium containing E2, either in the absence or presence of FSK. Gene expression analyses of UCP-1, Pgc-1α and resistin were performed in cultured cells. During 7 days of cold exposure, BW, RPAT mass and circulating triglycerides levels were affected by both temperature and surgery, with lower levels found in OVX-PF C rats. Nevertheless, when RPAT gene expression levels were analyzed, we found that while UCP-1 and DIO-2 diminished that of Pgc-1α enhanced in OVX-PF C group; conversely, β3AR did not vary. Similar data were found in cells from RT groups incubated with FSK. Indeed, a decrease in UCP-1 gene expression and an increase in that of Pgc-1α were noticed. In order to find a possible explanation, we noticed that E2 addition to APCs from SHX-RT cells showed a significant increase in both UCP-1 and Pgc-1α expression levels when stimulated with FSK. Considering both, in vivo and in vitro results, it can be concluded that RPAT pad-derived cells thermogenesis appears to be inhibited by prepuberal OVX (PICT2017-2334 and 2017-2314).