Time-restricted feeding mitigates high-fat diet-enhanced mammary tumorigenesis in MMTV-PyMT mice

Authors: Sundaram, Sneha; Yan, Lin

Submitted to: Nutrition Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/29/2018
Publication Date: 7/31/2018
Publication URL: https://handle.nal.usda.gov/10113/6119256
Citation: Sundaram, S., Yan, L. 2018. Time-restricted feeding mitigates high-fat diet-enhanced mammary tumorigenesis in MMTV-PyMT mice. Nutrition Research. http://doi.org/10.1016/j.nutres.2018.07.014.
DOI: https://doi.org/10.1016/j.nutres.2018.07.014

Interpretive Summary: More than one third of the US adults are obese or overweight. Obesity is a risk factor for breast cancer; it is positively associated with increased incidence and death rates of breast cancer in women. In addition to excessive food intake and lack of physical activity, overeating during the “wrong” time of the day may play a major role in development of obesity by disturbing the daily rhythm of energy metabolism and the balance between energy utilization and storage. We investigated whether restriction of food intake to the active-phase of the day (12 hours per day) affected mammary tumor growth in a mouse model of breast cancer. We found that feeding mice an obesity-causing, high-fat diet increased body fat mass and mammary tumor growth. Restricted feeding of the same high-fat diet to the active-phase of the day did not reduce energy intake but lowered body fat mass compared to unrestricted feeding of the high-fat diet. Furthermore, restricted feeding reduced the growth rate of mammary tumors and concentrations of cancer-promoting hormones in blood compared to the unrestricted feeding of the high-fat diet. Our findings indicate that in mice eating during the active-phase of the day reduces the body fat buildup and prevents the obesity-enhanced mammary tumor growth. It indicates that maintaining a healthy eating habit is beneficial in reducing the risk of obesity and associated diseases including breast cancer.

Technical Abstract: Obesity is a risk factor for breast cancer. Chronic overeating during the rest-phase of the day leads to obesity. In the present study, we tested the hypothesis that restricted feeding of a high-fat diet to the active-phase of the day reduces diet-enhanced mammary tumorigenesis in an MMTV-PyMT transgenic mouse model. Mice (female) were fed the standard AIN93G diet or a high-fat diet (16% or 45% of energy from soybean oil) with or without restricted feeding to the active-phase (dark-phase, 12 hours) over eight weeks of the study. Energy intake of the restricted group was similar to that of the high-fat group; the percent body fat mass was 16% lower in the restricted group than in the high-fat group. The median mammary tumor latency was 5.8, 7.0, and 6.4 weeks for the control, high-fat and restricted groups, respectively. The high-fat diet increased mammary tumor progression by 241% compared to the AIN93G diet; there was no significant difference in tumor progression between the restricted feeding and the AIN93G diet. The high-fat diet, compared to the AIN93G diet, significantly increased concentrations of leptin, monocyte chemoattractant protein-1, plasminogen activator inhibitor-1, angiopoietin-2, vascular endothelial growth factor, and hepatocyte growth factor in plasma. Restricted feeding, compared to the high-fat diet, reduced aforementioned variables in plasma. In conclusion, active-phase restricted feeding reduces diet-enhanced mammary tumorigenesis through decreasing body adiposity and associated inflammatory and angiogenic signals. These results support the concept that timing of food intake plays important role in alleviating metabolic disorders and related chronic diseases including breast cancer.