Effect of obesity in the mammary gland lipidome and its relation with cancer development

• Autor(a) principal: Pinho, Marisa Conceição Reis
• Data de Publicação: 2018
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10773/24587
• topic: Obesity; Breast cancer; PPARs; Lipid metabolism; Fatty acids; Lipidomic; PE; LPE; PC; LPC; SM; Cer; TAG; Mass spectrometry; Mammary gland

The prevalence of overweight and obesity is increasing worldwide and has been associated several comorbidities like cardiovascular diseases, hypertension, diabetes mellitus and other chronic diseases. In addition, more recently epidemiological studies have shown that obesity is associated with increased risk of many types of cancer, including breast cancer. Lipids have many functions, including cellular survival, proliferation, cell signaling and death, since they are involved in chemical-energy storage, cellular signaling, cell membranes, and cell–cell interactions. For this reason, any alterations in the lipid environment can bring severe alterations to the normal cell response to a situation, contributing to cancer development. Therefore, the objective of this work was to study the alterations in the lipidome of the mammary gland related to obesity and how those alterations may be related to the increase risk of developing breast cancer in obesity. For such, the mammary gland used were obtain from an animal model where obesity was induced by diet. The techniques used where Q-TOF (for triacylglycerol), GS-MS (for the fatty acids) and LC-MS (for the phospholipids). Our results show an increase in the levels of the triacylglycerol richer in fatty acid C18:2 (n-6). Those fatty acids have been reported to when oxidized produce aldehydes that form can form promutagenic adducts with DNA in human cells and thus may contribute to human cancers. In the phospholipids analyses we saw a decreased in the levels of phosphatidylcholines, more saturated and with more carbons, giving origin to more fluid cell membranes, a characteristic associated to cancer cells. In addition, we also saw a decreased in the levels of ceramides a lipid that has an anti-proliferative activity, showing this way that the normal apoptotic cells response may be impaired in obesity. Lastly, we also report a decrease in the levels of phosphatidylethanolamine and plasmyl-phosphatidylethanolamine which can be associated to a decrease in the antioxidant protection of membrane lipids. In sum, in obesity there is a modifications in the mammary gland lipidome that contributes for a higher predisposition to DNA mutations as well as, for an alteration in the apoptotic and autophagy response of cells, being that this may contribute to a higher risk of developing breast cancer