Papel da leptina presente em vesículas extracelulares liberadas pelo tecido adiposo de indivíduos com obesidade sobre células MDA-MB-231

• Ano de defesa: 2025
• Autor(a) principal: Encarnação, Carol Costa
• Outros Autores: [e-mail]
• Orientador(a): Martins, Mariana Renovato
• Banca de defesa: Pires, Bruno Ricardo Barreto , Silva, Rafael Brito da , Silva, Simone Vargas da
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade do Estado do Rio de Janeiro
• Programa de Pós-Graduação: Programa de Pós-Graduação em Biociências
• Departamento: Centro Biomédico::Instituto de Biologia Roberto Alcantara Gomes
• País: Brasil
• Palavras-chave em Português: leptina; obesidade - complicações; tecido adiposo; vesículas extracelulares; câncer de mama; Reprogramação Metabólica; Células MDA-MB-231 – Metabolismo
• Palavras-chave em Inglês: leptin; obesity; adipose tissue; extracellular vesicles; breast cancer
• Área do conhecimento CNPq: CIENCIAS BIOLOGICAS::FARMACOLOGIA::FARMACOLOGIA BIOQUIMICA E MOLECULAR
• Link de acesso: http://www.bdtd.uerj.br/handle/1/24371

Leptin is recognized as a link between obesity and breast cancer, two significant health issues. Secreted by adipose tissue (AT) in a soluble form or within extracellular vesicles (EVs) – with increased levels in obesity – leptin acts at various stages of tumor progression. In this study, we investigated the impacts of leptin contained in EVs released by obese AT on the functional properties and metabolism of triple-negative breast cancer cells (MDA-MB-231). MDA-MB-231 cells were treated with EVs released by subcutaneous AT depots collected from eutrophic (EVs EUT) or obese (EVs OB) individuals, in the presence or absence of a leptin receptor antagonist (HSLA); leptin was used as a positive control. Our results demonstrated that, after treatment with EVs OB, MDA-MB-231 cells underwent STAT3 phosphorylation and showed increased cell migration, a process dependent on fatty acid oxidation (FAO). These properties were reduced in the presence of the leptin receptor antagonist. Additionally, EVs OB induced a decrease in both lactate content and pyruvate kinase (PK) activity, while increasing glucose-6-phosphate dehydrogenase (G6PDH) activity. Simultaneously, EVs OB altered mitochondrial dynamics and enhanced the invasive capacity of MDA-MB-231 cells, likely due to matrix metalloproteinase-9 (MMP-9) activity. Our data indicate that leptin in EVs released by AT from individuals with obesity increases the malignancy of MDA-MB-231 cells by altering functional parameters and promoting metabolic reprogramming. These findings shed light on how AT modulates breast cancer cell behavior during obesity, highlighting the role of EVs and leptin in this process