Effects of dietary energy repletion and IGF-1 infusion on the inhibition of mammary carcinogenesis by dietary energy restriction

Abstract

Dietary energy restriction (DER) is a potent inhibitor of mammary carcinogenesis, but the responsible mechanisms are not fully understood. In a number of model systems, DER is associated with a decrease in circulating levels of IGF‐1. Moreover, we have recently reported that protection against cancer is lost, and plasma IGF‐1 levels are restored to control values when animals are re‐fed, i.e., energy repleted (DER‐REP). Accordingly, an experiment was designed to determine if infusion of IGF‐1 could mimic the effect of DER‐REP on the carcinogenic response in animals that were DER. Following 1‐methyl‐1‐nitrosourea injection (50 mg/kg), rats were fed either ad libitum (AL) or 40% DER. After 6 wk, the DER group was divided into three groups: (1) continued DER, (2) DER‐REP, or (3) continued DER and infused with 120 μg rh‐IGF‐1/d (INF) for a duration of 8 d. DER reduced mammary cancer incidence and multiplicity (P < 0.01) versus AL rats. In rats that were DER‐REP, cancer incidence increased 1.4‐fold and multiplicity increased by 3.6‐fold versus DER rats. Plasma IGF‐1 were reduced by DER (P < 0.01), an effect that was reversed by DER‐REP (P < 0.05). INF increased plasma IGF‐1 versus DER rats (P < 0.01) but did not reverse the carcinogenic response. Plasma IGFBP‐3 levels were reduced by DER (P < 0.01), but elevated by either REP or INF. Thus, an 8‐d period of refeeding following chronic DER (DER‐REP) reversed the anticancer effects of DER, and 8 d of IGF‐1 infusion without refeeding (INF) did not mimic the effects of the DER‐REP on the carcinogenic response.