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Dietary effects on liver tumor burden in mice treated with the hepatocellular carcinogen diethylnitrosamine.
J Hepatol 2015; 62(3):599-606JH

Abstract

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.

Authors+Show Affiliations

Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA.Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA.Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA.Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA.Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA.Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA.Institute of Pathology, Medical University of Graz, Graz, Austria.Department of Medicine, University of Virginia, Charlottesville, VA 22908, USA; Emily Couric Clinical Cancer Center, University of Virginia, Charlottesville, VA 22908, USA.Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA; Department of Medicine, University of Virginia, Charlottesville, VA 22908, USA; Emily Couric Clinical Cancer Center, University of Virginia, Charlottesville, VA 22908, USA; School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia. Electronic address: klh8st@virginia.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

25450719

Citation

Healy, Marin E., et al. "Dietary Effects On Liver Tumor Burden in Mice Treated With the Hepatocellular Carcinogen Diethylnitrosamine." Journal of Hepatology, vol. 62, no. 3, 2015, pp. 599-606.
Healy ME, Chow JD, Byrne FL, et al. Dietary effects on liver tumor burden in mice treated with the hepatocellular carcinogen diethylnitrosamine. J Hepatol. 2015;62(3):599-606.
Healy, M. E., Chow, J. D., Byrne, F. L., Breen, D. S., Leitinger, N., Li, C., ... Hoehn, K. L. (2015). Dietary effects on liver tumor burden in mice treated with the hepatocellular carcinogen diethylnitrosamine. Journal of Hepatology, 62(3), pp. 599-606. doi:10.1016/j.jhep.2014.10.024.
Healy ME, et al. Dietary Effects On Liver Tumor Burden in Mice Treated With the Hepatocellular Carcinogen Diethylnitrosamine. J Hepatol. 2015;62(3):599-606. PubMed PMID: 25450719.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dietary effects on liver tumor burden in mice treated with the hepatocellular carcinogen diethylnitrosamine. AU - Healy,Marin E, AU - Chow,Jenny D Y, AU - Byrne,Frances L, AU - Breen,David S, AU - Leitinger,Norbert, AU - Li,Chien, AU - Lackner,Carolin, AU - Caldwell,Stephen H, AU - Hoehn,Kyle L, Y1 - 2014/10/23/ PY - 2014/05/05/received PY - 2014/09/22/revised PY - 2014/10/09/accepted PY - 2014/12/3/entrez PY - 2014/12/3/pubmed PY - 2015/12/15/medline KW - Fructose KW - Inflammation KW - Insulin resistance KW - Liver cancer KW - Obesity KW - Sugar SP - 599 EP - 606 JF - Journal of hepatology JO - J. Hepatol. VL - 62 IS - 3 N2 - 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. SN - 1600-0641 UR - https://www.unboundmedicine.com/medline/citation/25450719/Dietary_effects_on_liver_tumor_burden_in_mice_treated_with_the_hepatocellular_carcinogen_diethylnitrosamine_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0168-8278(14)00785-5 DB - PRIME DP - Unbound Medicine ER -