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

Autor:	Lambertz IU; Department of Molecular and Cellular Medicine, Texas A&M Health Science Center, Texas A&M University, College Station, Texas., Luo L; Department of Molecular and Cellular Medicine, Texas A&M Health Science Center, Texas A&M University, College Station, Texas., Berton TR; Department of Biology, Austin Community College, Austin, Texas., Schwartz SL; Galvanize, Inc., Instructor, Sr. Data Scientist, Austin, Texas., Hursting SD; Department of Nutrition, University of North Carolina, Chapel Hill, North Carolina.; Department of Nutritional Sciences, University of Texas, Austin, Texas., Conti CJ; Department of Bioengineering, Tissue Engineering and Regenerative Medicine Group (TERMeG), Universidad Carlos III de Madrid, Madrid, Spain.; Instituto de Investigación Sanitaria de la Fundación Jimenez Diaz (IIS-FJD), Madrid, Spain., Fuchs-Young R; Department of Molecular and Cellular Medicine, Texas A&M Health Science Center, Texas A&M University, College Station, Texas. fuchs-young@medicine.tamhsc.edu.
Jazyk:	angličtina
Zdroj:	Cancer prevention research (Philadelphia, Pa.) [Cancer Prev Res (Phila)] 2017 Oct; Vol. 10 (10), pp. 553-562. Date of Electronic Publication: 2017 Sep 13.
DOI:	10.1158/1940-6207.CAPR-17-0131
Abstrakt:	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 AACR See related editorial by Freedland, p. 551-2 . (©2017 American Association for Cancer Research.)
Databáze:	MEDLINE
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