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Cancer Prev Res (Phila). 2017 Oct;10(10):553-562. doi: 10.1158/1940-6207.CAPR-17-0131. Epub 2017 Sep 13.

Early Exposure to a High Fat/High Sugar Diet Increases the Mammary Stem Cell Compartment and Mammary Tumor Risk in Female Mice.

Author information

1
Department of Molecular and Cellular Medicine, Texas A&M Health Science Center, Texas A&M University, College Station, Texas.
2
Department of Biology, Austin Community College, Austin, Texas.
3
Galvanize, Inc., Instructor, Sr. Data Scientist, Austin, Texas.
4
Department of Nutrition, University of North Carolina, Chapel Hill, North Carolina.
5
Department of Nutritional Sciences, University of Texas, Austin, Texas.
6
Department of Bioengineering, Tissue Engineering and Regenerative Medicine Group (TERMeG), Universidad Carlos III de Madrid, Madrid, Spain.
7
Instituto de Investigación Sanitaria de la Fundación Jimenez Diaz (IIS-FJD), Madrid, Spain.
8
Department of Molecular and Cellular Medicine, Texas A&M Health Science Center, Texas A&M University, College Station, Texas. fuchs-young@medicine.tamhsc.edu.

Abstract

Obesity and alterations in metabolic programming from early diet exposures can affect the propensity to disease in later life. Through dietary manipulation, developing mouse pups were exposed to a hyperinsulinemic, hyperglycemic milieu during three developmental phases: gestation, lactation, and postweaning. Analyses showed that a postweaning high fat/high sugar (HF/HS) diet had the main negative effect on adult body weight, glucose tolerance, and insulin resistance. However, dimethylbenz[a]anthracene (DMBA)-induced carcinogenesis revealed that animals born to a mother fed a HF/HS gestation diet, nursed by a mother on a mildly diet-restricted, low fat/low sugar diet (DR) and weaned onto a HF/HS diet (HF/DR/HF) had the highest mammary tumor incidence, while HF/HF/DR had the lowest tumor incidence. Cox proportional hazards analysis showed that a HF/HS postweaning diet doubled mammary cancer risk, and a HF/HS diet during gestation and postweaning increased risk 5.5 times. Exposure to a HF/HS diet during gestation, when combined with a postweaning DR diet, had a protective effect, reducing mammary tumor risk by 86% (HR = 0.142). Serum adipocytokine analysis revealed significant diet-dependent differences in leptin/adiponectin ratio and IGF-1. Flow cytometry analysis of cells isolated from mammary glands from a high tumor incidence group, DR/HF/HF, showed a significant increase in the size of the mammary stem cell compartment compared with a low tumor group, HF/HF/DR. These results indicate that dietary reprogramming induces an expansion of the mammary stem cell compartment during mammary development, increasing likely carcinogen targets and mammary cancer risk. Cancer Prev Res; 10(10); 553-62. ©2017 AACRSee related editorial by Freedland, p. 551-2.

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