title: Exposure to lard-based high-fat diet during fetal and lactation periods modifies breast cancer susceptibility in adulthood in rats.
abstract: The present study investigated whether early life exposure to high levels of animal fat increases breast cancer risk in adulthood in rats. Dams consumed a lard-based high-fat (HF) diet (60% fat-derived energy) or an AIN93G control diet (16% fat-derived energy) during gestation or gestation and lactation. Their 7-week-old female offspring were exposed to 7,12-dimethyl-benzo[a]anthracene to induce mammary tumors. Pregnant dams consuming an HF diet had higher circulating leptin levels than pregnant control dams. However, compared to the control offspring, significantly lower susceptibility to mammary cancer development was observed in the offspring of dams fed an HF diet during pregnancy (lower tumor incidence, multiplicity and weight), or pregnancy and lactation (lower tumor multiplicity only). Mammary epithelial elongation, cell proliferation (Ki67) and expression of NFκB p65 were significantly lower and p21 expression and global H3K9me3 levels were higher in the mammary glands of rats exposed to an HF lard diet in utero. They also tended to have lower Rank/Rankl ratios (P=.09) and serum progesterone levels (P=.07) than control offspring. In the mammary glands of offspring of dams consuming an HF diet during both pregnancy and lactation, the number of terminal end buds, epithelial elongation and the BCL-2/BAX ratio were significantly lower and serum leptin levels were higher than in the controls. Our data confirm that the breast cancer risk of offspring can be programmed by maternal dietary intake. However, contrary to our expectation, exposure to high levels of lard during early life decreased later susceptibility to breast cancer.
authors.affiliation: Faculty of Pharmaceutical Sciences.
authors.forename: Fábia
authors.initials: F
authors.lastname: de Oliveira Andrade
authors.affiliation: Faculty of Pharmaceutical Sciences.
authors.forename: Camile Castilho
authors.initials: CC
authors.lastname: Fontelles
authors.affiliation: Faculty of Pharmaceutical Sciences.
authors.forename: Mariana Papaléo
authors.initials: MP
authors.lastname: Rosim
authors.affiliation: Faculty of Pharmaceutical Sciences.
authors.forename: Tiago Franco
authors.initials: TF
authors.lastname: de Oliveira
authors.affiliation: Faculty of Pharmaceutical Sciences.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: de Melo Loureiro
authors.affiliation: Faculty of Pharmaceutical Sciences.
authors.forename: Jorge
authors.initials: J
authors.lastname: Mancini-Filho
authors.affiliation: School of Public Health, University of São Paulo.
authors.forename: Marcelo Macedo
authors.initials: MM
authors.lastname: Rogero
authors.affiliation: Faculty of Pharmaceutical Sciences; Food and Nutrition Research Center (NAPAN), São Paulo, Brazil.
authors.forename: Fernando Salvador
authors.initials: FS
authors.lastname: Moreno
authors.affiliation: Georgetown University Lombardi Comprehensive Cancer Center, Washington, DC, USA.
authors.forename: Sonia
authors.initials: S
authors.lastname: de Assis
authors.affiliation: State University of São Paulo, Botucatu, Brazil.
authors.forename: Luiz Fernando
authors.initials: LF
authors.lastname: Barbisan
authors.affiliation: Georgetown University Lombardi Comprehensive Cancer Center, Washington, DC, USA.
authors.forename: Leena
authors.initials: L
authors.lastname: Hilakivi-Clarke
authors.affiliation: Faculty of Pharmaceutical Sciences; Food and Nutrition Research Center (NAPAN), São Paulo, Brazil. Electronic address: tong@usp.br.
authors.forename: Thomas Prates
authors.initials: TP
authors.lastname: Ong
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001943:Breast Neoplasms / Q000097:blood / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D059305:Diet, High-Fat / Q000009:adverse effects*; D004041:Dietary Fats / Q000009:adverse effects / Q000627:therapeutic use; D060467:Disease Resistance; D005260:Female; D047109:Fetal Development; D018507:Gene Expression Regulation, Developmental; D053208:Kaplan-Meier Estimate; D007774:Lactation; D020738:Leptin / Q000819:agonists / Q000097:blood; D008321:Mammary Glands, Animal / Q000378:metabolism / Q000473:pathology*; D039382:Maternal Nutritional Physiological Phenomena; D011247:Pregnancy; D011374:Progesterone / Q000037:antagonists & inhibitors / Q000097:blood; D017207:Rats, Sprague-Dawley; D047368:Tumor Burden
chemical_list: D015415:Biomarkers; D004041:Dietary Fats; D020738:Leptin; D011374:Progesterone; D015127:9,10-Dimethyl-1,2-benzanthracene; C029310:lard
keywords: Breast cancer; Fetal programming; H3K9me3; High-fat diet; RANK/RANKL pathway
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