High-Fat, High-Sucrose, and High-Cholesterol Diets Accelerate Tumor Growth and Metastasis in Tumor-Bearing Mice

Abstract

Epidemiological studies indicate that the risk factors for the development of various cancers are closely associated with metabolic symptoms such as obesity, hyperlipidemia, and insulin resistance caused by the excess consumption of high-calorie diets. However, the mechanisms of tumor growth and metastasis caused by feeding a high-calorie diet have not been clarified yet in tumor-bearing mice. In this study, we examined the effects of a high-fat (HF), a high-sucrose (HS), a high-cholesterol (HC) or a low-fat/low-sucrose (LF/LS) diet on tumor growth and metastasis in tumor-bearing mice. Angiogenic factors such as plasma leptin and monocyte chemoattractant protein-1 (MCP-1) were increased after the implantation of tumors, whereas conversely, an antiangiogenic factor, adiponectin, was reduced after the implantation of tumors in mice fed the HF, the HS, or the HC diet compared to LF/LS diet. Furthermore, we found that vascular endothelial growth factor, hypoxia inducible factor-1α and MCP-1 expression levels in tumors of mice fed the HF, the HS, or the HC diet were increased compared to those of mice fed the LF/LS diet. These findings suggest that the acceleration of tumor growth and metastasis by feeding the 3 diets may be due to the increase of angiogenic factors and the reduction of antiangiogenic factors.

Acknowledgments and Notes

This work was supported in part by Grants-in-Aid from Kao Research Council for the Study of Healthcare Science (Tokyo, Japan) and for Scientific Research on Priority Areas (No. 17035059) from The Ministry of Education, Culture, Sports, Science and Technology.

Notes

^a : Mineral and vitamin mixtures (AIN-76) were purchased from Oriental Yeast (Osaka, Japan).

^a :Values are means ± SE of 8 animals per groups. Abbreviations are as follows: LLC, Lewis lung carcinoma; LF/LS, low-fat/low sucrose diet; HF, high-fat diet; HS, high-sucrose diet; HC, high-cholesterol diet; TC, total cholesterol; TG, triacylglycerol; NEFA, nonesterified fatty acid.

^b : P < 0.05 compared with control diet.

^c : P < 0.05 compared with HS diet.

^d : P < 0.05 compared with HF diet.

^e : P < 0.05 compared with HC diet.

^f : P < 0.05 compared with non-tumor-bearing mice fed the same diet.

^a : Values are means ± SE of 8 animals per group. Abbreviations are as follows: HIF-1α, hypoxic inducible factor; vWF, von Willebrand Factor; HS, high sucrose; HF, high fat; HC, high cholesterol.

^b : P < 0.05 compared with control diet.