Please use this identifier to cite or link to this item: https://ninho.inca.gov.br/jspui/handle/123456789/12101
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dc.contributor.authorBastos, Narayana Fazolini Paula-
dc.contributor.authorCruz, André Luiz de Souza-
dc.contributor.authorWerneck, Miriam Bianchi de Frontin-
dc.contributor.authorViola, Joao Paulo de Biaso-
dc.contributor.authorMonteiro, Clarissa Menezes Maya-
dc.contributor.authorViola, Patricia Torres Bozza-
dc.date.accessioned2022-12-27T14:00:22Z-
dc.date.available2022-12-27T14:00:22Z-
dc.date.issued2015-
dc.identifier.issn1551-4005-
dc.identifier.urihttps://ninho.inca.gov.br/jspui/handle/123456789/12101-
dc.description.abstractAccumulating 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-β 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-β 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 obesity-related enhanced susceptibility to colon carcinoma.pt_BR
dc.subjectLeptinapt_BR
dc.subjectLeptinpt_BR
dc.subjectGotículas Lipídicaspt_BR
dc.subjectLipid Dropletspt_BR
dc.subjectSirolimopt_BR
dc.subjectSirolimuspt_BR
dc.subjectSerina-Treonina Quinases TORpt_BR
dc.subjectTOR Serine-Threonine Kinasespt_BR
dc.titleLeptin activation of mTOR pathway in intestinal epithelial cell triggers lipid droplet formation, cytokine production and increased cell proliferationpt_BR
dc.TypeArticlept_BR
Appears in Collections:Artigos de Periódicos da Pesquisa Experimental e Translacional



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