EFFECTS OF PERITUMORAL ADIPOCYTE-SECRETED FACTORS ON LIPOLYTIC ACTIVITY AND MITOCHONDRIAL FUNCTION OF MATURE 3T3L1 ADIPOCYTES.

GANTOV M; SANTISO N; AMATO AR; PAGNOTTA P; CROSBIE ML; FRASCAROLLI MC; TONEATTO J; DRESZMAN R; URSINO A; CALVO JC

Mar del Plata

Congreso; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC).; 2019

SAIC

Abstract/Resumen: Adipose microenvironment is involved in signaling pathways that influence breast cancer progression. However, adipocyte characteristics involved in this process remain poorly understood. We have previously demonstrated that adipocytes exposed to conditioned media from human adipose tissue explants of tumor breasts (hATT-CMs) displayed characteristics that morphologically resembled brown adipocytes with high expression of mitochondrial UCP1 and other thermogenic proteins. Lipolysis is a prerequisite for thermogenesis in brown and beige adipocytes. Hence, our next aim was to examine the possibility that hATT induced changes in mitochondrial architecture as well as expression and subcellular localization of lipolytic proteins that could contribute to beige thermogenesis. Small and round-shaped mitochondria, partially swelled, were observed in adipocytes 3T3-L1 exposed to hATT- CMs, in comparison to treated with hATN-CMs, which displayed a mix of tubular and spherical mitochondria like control adipocytes. Interestingly, adipocytes exposed to hATT-CMs showed increased HSL and perilipin expression levels, and the number of micro- lipid droplets (LDs), which were stained for a discontinue intensity signal of perilipin in a similar manner to adipocytes treated with rosiglitazone. Contrarily, adipocytes exposed to hATN-CMs increased LDs size, without affecting HSL and perilipin expression levels and perilipin subcellular localization. Importantly, the activated form of HSL was able to translocate to the LD surface in response to the activation of lipolysis when adipocytes 3T3-L1 were treated with hATN-CMs or hATT-CMs. In summary, these findings suggest that hATT secrete a different set of factors compared to hATN, which may induce mitochondrial fission and modify the lipolytic activity of mature adipocytes. This would indicate a loss of normal functions in mature adipocytes (such as energy storage) attached to the tumor, in support of others that might favor tumor growth.