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Cyclic Food Restriction Alters Substrate Utilization and Abolishes Protection from Mammary Carcinogenesis in Female Rats^1,2,3,

Anthony R. Tagliaferro⁴, Anne M. Ronan, Loren D. Meeker^*, Henry J. Thompson, Amy L. Scott and Debajyoti Sinha^*

Department of Animal and Nutritional Sciences ^* Department of Mathematics, University of New Hampshire, Durham, NH 03824 Division of Laboratory Research, AMC Cancer Research Center, Denver, CO 80214

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.

KEY WORDS: • food restriction • mammary carcinogenesis • energy metabolism • substrate utilization • rats

¹ Preliminary findings were presented at Experimental Biology 94, April 1994, Anaheim, CA [Tagliaferro, A. R., Ronan, A. M., Meeker, L. D. & Thompson, H. J. (1994) Promotional effects of yo-yo dieting on mammary carcinogenesis. FASEB J. 8: A211 (abs.)].

² Supported in part by a grant from the American Institute for Cancer Research (grant 91A21 to Anthony R. Tagliaferro) and in part by Public Health Service grant CA52626 to Henry J. Thompson.

³ The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

⁴ To whom correspondence and reprint requests should be addressed.

Manuscript received 21 November 1994. Revision accepted 23 January 1996.

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