Dietary energy restriction reduces high-fat diet-enhanced metastasis of Lewis lung carcinoma in mice - PubMed (original) (raw)

Dietary energy restriction reduces high-fat diet-enhanced metastasis of Lewis lung carcinoma in mice

Sneha Sundaram et al. Oncotarget. 2016.

Abstract

The objective of this study was to determine whether a reduction in energy intake ameliorated the high-fat diet-enhanced spontaneous metastasis of Lewis lung carcinoma in mice. Male C57BL/6 mice were fed the AIN93G diet, a high-fat diet or a high-fat diet with a 5% restriction of the intake. Energy restriction reduced body adiposity and body weight, but maintained growth similar to mice fed the AIN93G diet. The high-fat diet significantly increased the number and size (cross-sectional area and volume) of metastases formed in lungs. Restricted feeding reduced the number of metastases by 23%, metastatic cross-sectional area by 32% and volume by 45% compared to the high-fat diet. The high-fat diet elevated plasma concentrations of proinflammatory cytokines (monocyte chemotactic protein-1, plasminogen activator inhibitor-1, leptin), angiogenic factors (vascular endothelial growth factor, tissue inhibitor of metalloproteinase-1) and insulin. Restricted feeding significantly reduced the high-fat diet-induced elevations in plasma concentrations of proinflammatory cytokines, angiogenic factors and insulin. These results demonstrated that a reduction in diet intake by 5% reduced high-fat diet-enhanced metastasis, which may be associated with the mitigation of adiposity and down-regulation of cancer-promoting proinflammatory cytokines and angiogenic factors.

Keywords: Lewis lung carcinoma; energy restriction; high-fat diet; metastasis; mice.

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Conflict of interest statement

CONFLICTS OF INTEREST

The authors have declared that no competing interests exist.

Figures

Figure 1

Figure 1. Restricted feeding reduces body weight in mice fed a high-fat diet

Values are means ± SEM (n = 35-38 per group). Mice fed the high-fat diet were heavier than those fed the AIN93G diet; the difference was significant two weeks after the initiation of experimental feeding (p < 0.05). Restricting diet intake by 5% reduced body weight of mice fed the high-fat diet; the difference was significant one week after the initiation of restricted feeding (p < 0.05).

Figure 2

Figure 2. Effects of restricted feeding on a. fat mass: body mass ratio b. lean mass: body mass ratio c. lean mass weight and d. energy intake in mice fed a high-fat diet

Values (means ± SEM) with different letters are significantly different at p < 0.05 (n = 35-38 per group, n = 6 for energy intake). AIN93G: AIN93G diet; HF: high-fat diet; HF-R: 5% restriction of the high-fat diet.

Figure 3

Figure 3. Restricted feeding reduces the a. number b. cross-sectional area and c. volume of lung metastases in mice fed the high-fat diet

Values (means ± SEM) with different letters are significantly different at p < 0.05 (n = 34-36 per group). AIN93G: AIN93G diet; HF: high-fat diet; HF-R: 5% restriction of the high-fat diet.

Figure 4

Figure 4. Effects of restricted feeding on plasma concentrations of a. MCP-1 b. PAI-1 c. VEGF d. TIMP-1 e. leptin and f. insulin in mice fed the high-fat diet

Values (means ± SEM) with different letters are significantly different at p < 0.05 (n = 10 per group). Ctl: non-tumor-bearing mice fed the AIN93G diet; AIN: AIN93G diet; HF: High-fat diet; HF-R: 5% restriction of the high-fat diet.

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