Perirenal white adipose tissue browning, contributes to tumor development in kidney cancer

BRUNA, FLAVIA; GÓMEZ, SILVINA E; PISTONE CREYDT, V; FERRANDO, MATÍAS; MOYA MORALES, DAIANA L; TONEATTO, J; ROMEO, LEONARDO R; CARÓN, RUBÉN W.

Mar del Plata

Congreso; REUNIÓN ANUAL DE SOCIEDADES BIOCIENTÍFICAS SAIC . SAI . SAFIS; 2020

There are white, brown and beige adipocytes with different functions. Beige adipocytes are located in white adipose tissue (AT) and could be derived from pre-existing adipocytes that, when properly stimulated, undergo a process known as browning. Recent studies shows that AT associated with breast cancer suffer browning and contribute to tumor development. The factors and signaling pathways responsible for the browning process are unknown, as well as the role of the adipose tissue browning could have on the tumor. We recently demonstrated that human AT around kidney tumor (hRAT), showed a differential protein expression profile respect to AT from normal kidney (hRAN). In this work, we study the browning process in AT in hARTh and hRNA, evaluating the white and brown AT markers expression. The ATs were obtained from patients with tumor kidney (hRAT, n=21) and kidney donors (hRAN, n=20). The AT fragments were lysed and total proteins were obtained and 1) UCP1, TBX1, PPARɣ, c/EBPα, PGC1α, adiponectin and leptin were quantified by western blot; and 2) UCP1, PGC1α and HSP by immunohistochemistry. In addition, we incubated hRNA fragments with conditioned media (CMs) from tumor and non-tumor human renal epithelial cell lines for 48h, the tissues were lyzed and UCP1, TBX1 and PGC1α proteins were measured. Statistical differences among the groups were evaluated by one-way ANOVA with Tukey´s post hoc tests. We found UCP1, TBX1, PPARɣ, c/EBPα, PGC1α and leptin significantly increased in hRAT vs. hRAN explants (p˂0.05). In addition, perilipin (mature adipocyte marker) was significantly decreased in hRAT vs. hRAN (p˂0.05). Furthermore, UCP1, TBX1 and PGC1α expression were significantly increased in hRAN incubated with tumor cells-CMs vs. hRAN incubated with non tumor cells-CMs (p˂0.05). This would indicate that the renal tumor cells secrete soluble factors stimulating the surrounding adipose tissue browning. The AT browning could fulfill a regulatory function on the tumor.