Obesity is a risk factor for breast cancer. Chronic overeating during the rest phase of the day leads to metabolic dysfunction and obesity. Lifestyle changes including restriction of meal times may be successful weight loss strategies. In the present study, we tested the hypothesis that restricted feeding of a high-fat diet to the dark phase (the active phase) of the day reduces diet-enhanced mammary tumorigenesis in an MMTV-PyMT transgenic mouse model. Mice (female) were fed the AIN93G diet (16% of energy from soybean oil) or the high-fat diet (45% of energy from soybean oil) with or without restricted feeding to the dark phase (12 hours) over eight weeks of the study. The body fat mass of the restricted feeding group was lower than the high-fat group but similar to the AIN93G control group. The mammary tumor latency was 5.8, 7.0, and 6.4 weeks for the control, high-fat and high-fat restricted groups, respectively. Restricted feeding reduced mammary tumor progression by 58% compared to the unrestricted feeding of the high-fat diet. Compared to the AIN93 diet, the high-fat diet significantly increased plasma concentrations of plasminogen activator inhibitor-1, monocyte chemoattractant protein-1, resistin, leptin, insulin, angiopoietin-2, hepatocyte growth factor and vascular endothelial growth factor. The restricted feeding reduced concentrations of the aforementioned variables in plasma, except resistin, leptin, and insulin. In summary, restricted feeding of the high-fat diet to the dark phase reduces diet-enhanced mammary tumorigenesis. This protection of the restricted feeding against breast tumorigenesis may be associated with its actions in attenuating adipogenesis and production of related inflammatory cytokines and angiogenic factors.

Citation Format: Sneha Sundaram, Lin Yan. Restricted feeding of a high-fat diet to the dark phase of the day attenuates mammary tumorigenesis in MMTV-PyMT mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1271.