Effects of high fat diet on mammary gland duct epithelium and neoplastic disease progression in a metabolic syndrome mice model

FARRÉ, PL; DALTON, GN; MASSILLO, C; MEISS, R; DE SIERVI, A; SCALISE, G; PORRETTI, J; DE LUCA, P

Mar del Plata

Congreso; LXI Reunión de la Sociedad Argentina de Investigación Clínica; 2016

Sociedad Argentina de Investigación Clínica, Sociedad Argentina de Inmunología, Sociedad Argentina de Farmacología Experimental, Sociedad Argentina de Nanomedicina y Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio

Metabolic syndrome (MeS) is a cluster of pathophysiological disorders that comprises at least three of the following factors: abdominal obesity, elevated triglycerides, dyslipidemia, high blood pressure and elevated serum glucose levels. Several studies associated MeS with increased risk for several cancer types, including breast cancer. The aim of this work was to assess the effect ofhigh fat diet (HFD) on mammary gland epithelium development and lung and liver metastasis in mice. We generated a MeS model feeding mice with high fat diet (HFD) for 10 weeks. Control diet (CD)-fed animals were maintained at the same conditions. MDA-MB-231 breast tumor cells were implanted on their mammaryfat pad. After four weeks, tumors were surgically removed. Two weeks after surgery mice were sacrificed, and breast, liver and lung samples were collected for histopathological analysis. In addition, in the autopsy, representative samples of other unexpected findings were harvested. We found that 44% of mammary ducts from HFD mice were covered with prominent epithelial cells withnuclear pseudostratification and columnar changes. None of the animals in the control diet (CD) group developed these changes. We found lung metastasis in 20% of the HFD fed mice, while CD group showed no metastasis. We also found liver metastasis in 20% of the HFD fed mice, and only 10% on the CD group. In con -clusion, HFD induced early proliferative changes in the mammary duct epithelium, which can be a sign of a preneoplastic condition. The same group of mice had increased number of metastasis and more extended neoplastic disease than mice fed with CD. Altogether, our findings reveal that HFD induces proliferative changes in breast ducts, as well as progression of neoplastic disease.