Research Article
A high-corn-oil diet strongly stimulates mammary carcinogenesis, while a high-extra-virgin-olive-oil diet has a weak effect, through changes in metabolism, immune system function and proliferation/apoptosis pathways,☆☆

https://doi.org/10.1016/j.jnutbio.2018.11.001Get rights and content
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Abstract

Breast cancer is the most common malignancy in women worldwide, and dietary lipids are important environmental factors influencing its etiology. We have investigated the effects, and the mechanisms associated, of high-fat diets on 7,12-dimethylbenz(a)anthracene-induced rat mammary tumors. Animals were fed a low-fat, a high-corn-oil (HCO) or a high-extra-virgin-olive-oil (HOO) diet from weaning or after induction. The HCO diet had a clear stimulating effect on mammary carcinogenesis, especially when dietary intervention started after induction, whereas the tumors from HOO diet groups exhibited clinical and morphological characteristics similar to those from low-fat controls. Transcriptomic and further protein and immunohistochemical analyses of tumors also indicated different modulatory effects of high-fat diets affecting relevant biological functions: metabolism, immunosurveillance and proliferation/apoptosis pathways. Thus, the results suggested different metabolic adaptations with increased glycolysis by effect of HOO diet. Moreover, leukocyte tumor infiltration and inflammation mediators showed increased cytotoxic T cells and decreased TGFβ1 expression by the HOO diet, while the HCO one increased arginase expression and IL-1α plasma levels. Furthermore, the study of proteins controlling proliferation/apoptosis pathways (Sema3A, Stat5, Smad1, Casp3) suggested an increase in proliferation by the HCO diet and an increase of apoptosis by the diet rich in olive oil. In conclusion, the HCO diet clearly stimulated mammary carcinogenesis, especially in the promotion phase, and induced molecular changes suggesting increased tumor proliferation/apoptosis balance and a proinflammatory microenvironment. The HOO diet, despite being high fat, had a weaker effect on tumorigenesis probably related to metabolic adaptations, enhanced immunosurveillance and increased apoptosis.

Abbreviations

DMBA
7,12-dimethylbenz(a)anthracene
EVOO
extra-virgin olive oil
FA
fatty acids
GO
gene ontology
HCO
high corn oil
HOO
high extra-virgin olive oil
LF
low fat
MUFA
monounsaturated fatty acids
PUFA
polyunsaturated fatty acids

Keywords

Dietary lipids
Breast cancer
Olive oil
Transcriptome
Immune system
Apoptosis
Metabolism

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Funding: This work was supported by grants from “Plan Nacional de I+D+I” (AGL2006-07691); “Fundación Patrimonio Comunal Olivarero (FPCO)” (FPCO2008-165.396; FPCO2013-CF611.084); “Agencia para el Aceite de Oliva del Ministerio de Agricultura, Alimentación y Medio Ambiente” (AAO2008-165.471); “Organización Interprofesional del Aceite de Oliva Español (OIAOE)” (OIP2009-CD165.646), “Departaments de Salut i d'Agricultura, Alimentació i Acció Rural de la Generalitat de Catalunya” (GC2010-165.000), FPCO and OIAOE (FPCO-OIP2016-CF614.087).

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Author disclosures: no conflicts of interest.