Submitted to: Anticancer Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/20/2020
Publication Date: 7/1/2020
Citation: Yan, L., Sundaram, S., Rust, B.M., Picklo, M.J., Bukowski, M.R. 2020. The metabolome of mammary tumors differs from normal mammary glands but is not altered by time-restricted feeding under obesogenic conditions. Anticancer Research. https://doi.org/10.21873/anticanres.14358.
Interpretive Summary: Lifestyle changes in modern world (for example, overeating during a “wrong time” of the day) are environmental factors that disrupt the daily rhythms of physiological functions (for example, the eating/fasting pattern) and contribute to obesity. Obesity is a risk factor for breast cancer in women. We investigated whether restriction of food intake during the active phase of the day (the dark phase for rodents) affected metabolism in a mouse model of breast cancer. Compared to mice with unrestricted access to an obesity-causing, high-fat diet, restricted feeding of the same high-fat diet during the dark phase (12 hours per day) mitigated mammary tumor growth, reduced body fat mass, improved insulin sensitivity in mice, and reduced expression of genes that were responsible for lipid metabolism in mammary tumors. However, restricted feeding did not alter numerous primary metabolites in mammary tumors. Our findings indicate that the protection afforded by time-restricted feeding against breast cancer are likely due to changes in host-tumor interactions rather than a direct regulation of nutrients to the tumor.
Technical Abstract: Diet is an environmental factor that affects breast carcinogenesis. Time restricted feeding (TRF) of a high-fat diet (HFD) mitigates the enhancement of mammary tumorigenesis induced by ad libitum HFD intake in MMTV-PyMT mice, a model for breast cancer. With the goal of determining the effect of TRF on the metabolic profile of breast cancer, we performed untargeted metabolomic and targeted transcriptomic analyses on samples of mammary tumors from MMTV-PyMT mice provided a normal fat AIN93G diet ad libitum, a HFD ad libitum, or a HFD with TRF (12 hours, dark phase) and samples of mammary glands from wild-type mice provided the AIN93G diet ad libitum. The metabolic profile of mammary tumors differed significantly from that of mammary glands, but there was no impact of dietary treatments upon the tumor metabolome. TRF did reduce the elevated gene expression of Hmgcr, Srebp1, Fads2, and Ppard in MMTV-PYMT mammary tumors, indicating a down regulation of lipid metabolism. The null effect of TRF on the metabolomic profile does not rule out changes in more refined intracellular signaling pathways, but does suggest that the protection of TRF against mammary tumorigenesis may rely upon its action on host metabolism, evidenced by reported reduction in body adiposity and inflammation and improvement in insulin sensitivity.