Dietary effects on liver tumor burden in mice treated with the hepatocellular carcinogen diethylnitrosamine

JOURNAL OF HEPATOLOGY

卷:62

Article

Healy, Marin E.¹  Chow, Jenny D. Y.¹  Byrne, Frances L.¹  Breen, David S.¹  Leitinger, Norbert¹  Li, Chien¹  Lackner, Carolin⁴  Caldwell, Stephen H.^2,3  Hoehn, Kyle L.^1,2,3,5 

[1] Univ Virginia, Dept Pharmacol, Charlottesville, VA 22908 USA

[2] Univ Virginia, Dept Med, Charlottesville, VA 22908 USA

[3] Univ Virginia, Emily Cour Clin Canc Ctr, Charlottesville, VA 22908 USA

[4] Med Univ Graz, Inst Pathol, Graz, Austria

[5] Univ New S Wales, Sch Biotechnol & Biomol Sci, Sydney, NSW, Australia

关键词: Liver cancer;    Fructose;    Sugar;    Obesity;    Insulin resistance;    Inflammation;   

DOI  :  10.1016/j.jhep.2014.10.024

来源: Elsevier

【 摘 要 】

Background & Aims: Mice exposed to the hepatocellular carcinogen diethylnitrosamine at 2 weeks of age have a high risk of developing primary liver tumors later in life. Previous studies have demonstrated that diethylnitrosamine-treated mice have increased tumor burden when fed an obesigenic Western'' diet rich in lard fat and sugar. However, the role of dietary fats vs. sugars in the promotion of liver cancer is poorly understood. The aim of this study was to determine how altering dietary fats vs. sugars affects tumor burden in the diethylnitrosamine model. Methods: C57BL/6N mice were treated with diethylnitrosamine at 2 weeks of age and, from 6 to 32 weeks of age, fed one of five diets that differed in fat and sugar content, including normal chow, ketogenic, and Western diets. Results: Mice fed sugar-rich diets had the greatest tumor burden irrespective of dietary fat content. In contrast, mice fed a high-fat low-sugar diet had the least tumor burden despite obesity and glucose intolerance. When evaluated as independent variables, tumor burden was positively correlated with hepatic fat accumulation, postprandial insulin, and liver IL-6, and inversely correlated with serum adiponectin. In contrast, tumor burden did not correlate with adiposity, fasting insulin, or glucose intolerance. Furthermore, mice fed high sugar diets had lower liver expression of p21 and cleaved caspase-3 compared to mice fed low sugar diets. Conclusions: These data indicate that dietary sugar intake contributes to liver tumor burden independent of excess adiposity or insulin resistance in mice treated with diethylnitrosamine. (C) 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

【 授权许可】

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