Por favor, use este identificador para citar o enlazar este ítem:
https://www.arca.fiocruz.br/handle/icict/13777
Tipo
ArtículoDerechos de autor
Acceso restringido
Colecciones
- IOC - Artigos de Periódicos [12642]
Metadatos
Mostrar el registro completo del ítem
LEPTIN ACTIVATION OF MTOR PATHWAY IN INTESTINAL EPITHELIAL CELL TRIGGERS LIPID DROPLET FORMATION, CYTOKINE PRODUCTION AND INCREASED CELL PROLIFERATION
Autor
Afiliación
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.
Instituto Nacional de Câncer (INCA). Divisão de Biologia Celular. Rio de Janeiro, RJ, Brasil.
Instituto Nacional de Câncer (INCA). Divisão de Biologia Celular. Rio de Janeiro, RJ, Brasil.
Instituto Nacional de Câncer (INCA). Divisão de Biologia Celular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.
Instituto Nacional de Câncer (INCA). Divisão de Biologia Celular. Rio de Janeiro, RJ, Brasil.
Instituto Nacional de Câncer (INCA). Divisão de Biologia Celular. Rio de Janeiro, RJ, Brasil.
Instituto Nacional de Câncer (INCA). Divisão de Biologia Celular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.
Resumen en ingles
Accumulating evidence suggests that obesity and enhanced inflammatory reactions are predisposing conditions for
developing colon cancer. Obesity is associated with high levels of circulating leptin. Leptin is an adipocytokine that is
secreted by adipose tissue and modulates immune response and inflammation. Lipid droplets (LD) are organelles
involved in lipid metabolism and production of inflammatory mediators, and increased numbers of LD were observed
in human colon cancer. Leptin induces the formation of LD in macrophages in a PI3K/mTOR pathway-dependent
manner. Moreover, the mTOR is a serine/threonine kinase that plays a key role in cellular growth and is frequently
altered in tumors. We therefore investigated the role of leptin in the modulation of mTOR pathway and regulation of
lipid metabolism and inflammatory phenotype in intestinal epithelial cells (IEC-6 cells). We show that leptin promotes a
dose- and time-dependent enhancement of LD formation. The biogenesis of LD was accompanied by enhanced CXCL1/
CINC-1, CCL2/MCP-1 and TGF-b production and increased COX-2 expression in these cells. We demonstrated that
leptin-induced increased phosphorylation of STAT3 and AKT and a dose and time-dependent mTORC activation with
enhanced phosphorilation of the downstream protein P70S6K protein. Pre-treatment with rapamycin significantly
inhibited leptin effects in LD formation, COX-2 and TGF-b production in IEC-6 cells. Moreover, leptin was able to
stimulate the proliferation of epithelial cells on a mTOR-dependent manner. We conclude that leptin regulates lipid
metabolism, cytokine production and proliferation of intestinal cells through a mechanism largely dependent on
activation of the mTOR pathway, thus suggesting that leptin-induced mTOR activation may contribute to the obesityrelated
enhanced susceptibility to colon carcinoma.
Compartir