title: Dietary effects on liver tumor burden in mice treated with the hepatocellular carcinogen diethylnitrosamine.
abstract: OBJECTIVE
  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.affiliation: Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Marin E
authors.initials: ME
authors.lastname: Healy
authors.affiliation: Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Jenny D Y
authors.initials: JD
authors.lastname: Chow
authors.affiliation: Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Frances L
authors.initials: FL
authors.lastname: Byrne
authors.affiliation: Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Breen
authors.affiliation: Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Norbert
authors.initials: N
authors.lastname: Leitinger
authors.affiliation: Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Chien
authors.initials: C
authors.lastname: Li
authors.affiliation: Institute of Pathology, Medical University of Graz, Graz, Austria.
authors.forename: Carolin
authors.initials: C
authors.lastname: Lackner
authors.affiliation: Department of Medicine, University of Virginia, Charlottesville, VA 22908, USA; Emily Couric Clinical Cancer Center, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Caldwell
authors.affiliation: 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.
authors.forename: Kyle L
authors.initials: KL
authors.lastname: Hoehn
mesh_terms: D054392:Adipokines / Q000097:blood; D050154:Adiposity; D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D055423:Diet, Ketogenic / Q000009:adverse effects; D066273:Diet, Western / Q000009:adverse effects; D004040:Dietary Carbohydrates / Q000008:administration & dosage / Q000009:adverse effects*; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects*; D004052:Diethylnitrosamine / Q000633:toxicity*; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000209:etiology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications / Q000209:etiology / Q000378:metabolism; D047368:Tumor Burden
chemical_list: D054392:Adipokines; D002273:Carcinogens; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D018836:Inflammation Mediators; D004052:Diethylnitrosamine
keywords: Fructose; Inflammation; Insulin resistance; Liver cancer; Obesity; Sugar