Cyclic food restriction alters substrate utilization and abolishes protection from mammary carcinogenesis in female rats

We tested the hypothesis that cyclic food restriction abolishes protection against mammary carcinogenesis. Virgin female Sprague Dawley rats (n = 159) were injected intraperitoneally with 25 mg/kg n-methyl-n-nitrosourea at 50 d of age. Eleven days later, rats were given free access to a 24.6 g fat/100 g AIN-76A diet (ad lib-c), fed in two meals (me-c), or fed in two meals restricted in weight by 33% for 1 wk followed by 3 wk of compensatory refeeding (me-r) for 18 wk or 4.5 restriction cycles. Energy and substrate utilization of 15 rats from each group was measured by indirect calorimetry. The me-r rats ate and weighed less (P < 0.0001), had a greater efficiency of food utilization (P < 0.01), and had a 12% higher incidence of mammary cancer (P < 0.0001) than ad lib-c rats after adjusting for the effect of final body weight. Resting metabolic rate was not different among groups, but me-r rats used less glucose during restriction and more glucose and less lipid for energy during body weight recovery than me-c rats (P < 0.0001). Increased energy efficiency and the shift in utilization of glucose and fatty acids followed closely the effects of cyclic food restriction and meal feeding on mammary carcinogenesis.