Feeding a High-Fat Diet for a Limited Duration Increases Cancer Incidence in a Breast Cancer Model

Abstract

High-fat intake by young Asian women impacts the risk of breast cancer. Understanding the underlying molecular mechanisms may be essential for disease prevention in Asia as well as globally. We aimed to examine the effects of corn oil- and animal fat-based high-fat diets (32.9 and 31.4%, respectively, of fat energy ratio as compared to 12.3% in the standard diet) on mammary carcinogenesis and alterations in gene expression and epigenetic statuses in the mammary gland during the growth stages in a rat model. An increased incidence of carcinomas was observed after the cessation of high-fat feeding. In addition, rapid tumor growth and elevations in Celsr2 expression, which may be a result of DNA hypomethylation patterns in the 3′ untranslated region of the gene were noted in the animal fat group. In the human breast carcinoma cell line MCF7, a marginal decrease in cell viability was observed following the knockdown of Celsr2, suggesting that the animal fat-associated risk of cancer is partly due to the deregulation of mammary cell proliferation via non-metabolic gene functions. The present results will contribute to the development of strategies for controlling the food-associated risk of breast cancer, particularly in younger age groups.

Acknowledgments

We thank Mr. N. Uchiya and the Animal Core Facility of the National Cancer Center Research Institute for maintaining the experimental rats and for their technical support with histopathological evaluations. The Core Facility was supported by the National Cancer Center Research and Development Fund (29-A-2).

Authors’ Contribution

Toshio Imai and Mie Naruse performed the animal and cell culture experiments, respectively. Yukino Machida contributed to the pathological analysis, and Gen Fujii, Masako Ochiai, and Mami Takahashi contributed to the biochemical analyses. Michihiro Mutoh and Hitoshi Nakagama contributed to data interpretation. Toshio Imai prepared and revised the manuscript, and was responsible for the study design and data analysis. All authors confirm the authenticity of the raw data and have read and approved the final manuscript.

Data Availability Statement

Supplementary data are available at DOI: 10.6084/m9.figshare.21194278.

Disclosure Statement

The authors report no conflict of interest

Additional information

Funding

This work was supported by the National Cancer Center Research and Development Fund under Grant number 26-A-8; and Grants-in-Aid for Cancer Research, for the Third-Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health, Labor and Welfare of Japan under Grant number H22-G-014.