Restricted feeding of a high‐fat diet reduces spontaneous metastases of Lewis lung carcinoma in C57BL/6 mice

Abstract

Obesity is a risk factor for cancer. We previously reported that consumption of a high‐fat diet enhances metastasis in mice (Yan, Clin Exp Metastasis 2010). The present study investigated the effects of restricted feeding of a high‐fat diet on spontaneous metastasis of Lewis lung carcinoma (LLC) in male C57BL/6 mice. Three‐week‐old mice were fed a low‐fat or high‐fat diet (16% or 45% of energy from corn oil). When significant differences in body weight between the groups were observed, the high‐fat diet‐fed mice were randomly assigned to 2 groups and fed the high‐fat diet either ad lib or with 5% restriction (on the basis of average daily intake of the ad lib fed group). Five weeks after the initiation of restricted feeding, mice were subcutaneously injected with 2.5×105 LLC cells. The resulting primary tumor was removed surgically 10 days later, and the experiment was terminated after an additional 10 days. Compared to mice fed the high‐fat diet ad lib, restricted feeding significantly reduced caloric intake, body fat mass and body weight to levels similar to those of low‐fat diet‐fed mice. Consumption of the high‐fat diet significantly increased the number and size of lung metastases compared to the low‐fat diet; restricted feeding significantly reduced both to the levels of mice fed the low‐fat diet. Furthermore, compared to the high‐fat diet ad lib feeding, restricted feeding significantly reduced plasma concentrations of insulin, inflammatory cytokines (leptin, plasminogen activator inhibitor‐1 and monocyte chemotactic protein‐1) and angiogenic factors (vascular endothelial growth factor and tissue inhibitor of metalloproteinase‐1). These results demonstrated that restricted feeding of the high‐fat diet reduced metastasis. It suggests that this reduction may be associated with the mitigation of adiposity and down‐regulation of related inflammatory cytokines and angiogenic factors.