Intermittent caloric restriction (ICR) provides greater prevention of mammary tumor (MT) development than chronic caloric restriction (CCR). Here we assessed the impact of a high‐fat diet on this protective effect in relation to serum IGF‐I, leptin and adiponectin.
At 10 wk of age MMTV‐TGF‐α female mice were assigned to AL (ad libitum 23% fat calories), ICR (3‐wk of 50% caloric restriction with 2× protein, fat, vitamins and minerals followed by 3‐wk of 100%AL mice's consumption) and CCR (calorie/nutrient intake matched to ICR for each 6‐wk cycle) groups (n=45/group). Food intakes were determined daily. Body weights, MT palpation and MT measurements were done weekly. Mice were followed until MT burden necessitated euthanasia or they reached 79 (end of restriction) or 82 (end of refeeding) weeks of age. Serum samples were obtained at baseline, euthanasia and cycles 5, 8, and 11 during restriction and refeeding for ICR mice.
Food intakes for ICR and CCR mice were 24.2% and 24.3% lower than AL mice (p<0.05). Body weights of ICR mice fluctuated in response to their calorie intake resulting in a significant difference among the groups. Final body, mammary and internal fat pad weights of AL mice were heaviest, followed by CCR and ICR‐refed mice. ICR‐restricted mice weights were the lowest. 66.7% of AL mice developed 1–5 MTs/mouse (grade 1–4). 52.3% of CCR mice had 1–3 MTs/mouse (grade 1–4). Only 4.4% of ICR mice developed 1 MT/mouse (grade 2).
ICR‐Restricted mice had significantly higher terminal serum IGFBP‐3 and lower IGF‐I and IGF‐1/IGFBP‐3 ratio than AL mice. There were no differences for CCR and ICR‐Refed mice compared to either AL or ICR‐Restricted groups. ICR‐Restricted mice had significantly lower serum leptin and significantly higher terminal adiponectin and adiponectin/leptin ratio compared to AL, CCR and ICR‐Refed mice. There were no differences in terminal serum measurements between mice with MTs versus those without MTs. IGF‐I of AL and CCR mice did not change with age whereas for ICR mice IGF‐1 was reduced during restriction periods. AL mice had the highest leptin levels across the study follow by CCR. For ICR mice leptin fluctuated in response to calorie intake, higher in refeeding vs restriction. Adiponectin levels for AL and CCR mice over time were similar. ICR mice had higher adiponectin levels when restricted vs refed. The adiponectin/leptin ratio of AL, CCR and ICR‐refed mice was dramatically lower across the study compared with baseline but for ICR‐restricted mice it was similar. These results indicate that ICR provides greater protection compared to CCR to prevent MT development even when a high fat diet is fed during refeeding. This was reflected by decreased MT incidence and MT burden and aggressiveness. Serum IGF‐I, adiponectin and leptin were significantly affected by periods of 50% restriction providing a milieu conducive to reduced MT development.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A110.