title: Dietary sugar intake increases liver tumor incidence in female mice.
abstract: Overnutrition can promote liver cancer in mice and humans that have liver damage caused by alcohol, viruses, or carcinogens. However, the mechanism linking diet to increased liver tumorigenesis remains unclear in the context of whether tumorigenesis is secondary to obesity, or whether nutrients like sugar or fat drive tumorigenesis independent of obesity. In male mice, liver tumor burden was recently found to correlate with sugar intake, independent of dietary fat intake and obesity. However, females are less susceptible to developing liver cancer than males, and it remains unclear how nutrition affects tumorigenesis in females. Herein, female mice were exposed to the liver carcinogen diethylnitrosamine (DEN) and fed diets with well-defined sugar and fat content. Mice fed diets with high sugar content had the greatest liver tumor incidence while dietary fat intake was not associated with tumorigenesis. Diet-induced postprandial hyperglycemia and fasting hyperinsulinemia significantly correlated with tumor incidence, while tumor incidence was not associated with obesity and obesity-related disorders including liver steatosis, glucose intolerance, or elevated serum levels of estrogen, ALT, and lipids. These results simplify the pathophysiology of diet-induced liver tumorigenesis by focusing attention on the role of sugar metabolism and reducing emphasis on the complex milieu associated with obesity.
authors.affiliation: Department of Pharmacology, University of Virginia, Charlottesville, VA, USA.
authors.forename: Marin E
authors.initials: ME
authors.lastname: Healy
authors.affiliation: Department of Pharmacology, University of Virginia, Charlottesville, VA, USA.
authors.forename: Sujoy
authors.initials: S
authors.lastname: Lahiri
authors.affiliation: Department of Pharmacology, University of Virginia, Charlottesville, VA, USA.
authors.forename: Stefan R
authors.initials: SR
authors.lastname: Hargett
authors.affiliation: Department of Pharmacology, University of Virginia, Charlottesville, VA, USA.
authors.forename: Jenny D Y
authors.initials: JD
authors.lastname: Chow
authors.affiliation: Department of Pharmacology, University of Virginia, Charlottesville, VA, USA.|School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia.
authors.forename: Frances L
authors.initials: FL
authors.lastname: Byrne
authors.affiliation: Department of Pharmacology, University of Virginia, Charlottesville, VA, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Breen
authors.affiliation: Department of Pharmacology, University of Virginia, Charlottesville, VA, USA.
authors.forename: Brandon M
authors.initials: BM
authors.lastname: Kenwood
authors.affiliation: Department of Pharmacology, University of Virginia, Charlottesville, VA, USA.
authors.forename: Evan P
authors.initials: EP
authors.lastname: Taddeo
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, USA.|Emily Couric Clinical Cancer Center, University of Virginia, Charlottesville, VA, USA.
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Caldwell
authors.affiliation: Department of Pharmacology, University of Virginia, Charlottesville, VA, USA.|Department of Medicine, University of Virginia, Charlottesville, VA, USA.|Emily Couric Clinical Cancer Center, University of Virginia, Charlottesville, VA, USA.|School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia.
authors.forename: Kyle L
authors.initials: KL
authors.lastname: Hoehn
mesh_terms: D050154:Adiposity; D000821:Animal Feed; D000818:Animals; D001835:Body Weight; D002273:Carcinogens / Q000633:toxicity; D004041:Dietary Fats; D019422:Dietary Sucrose; D004052:Diethylnitrosamine / Q000009:adverse effects; D005234:Fatty Liver / Q000209:etiology / Q000473:pathology; D005951:Glucose Tolerance Test; D006801:Humans; D015994:Incidence; D007328:Insulin / Q000378:metabolism; D008113:Liver Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology; D051379:Mice; D012307:Risk Factors; D012737:Sex Factors
chemical_list: D002273:Carcinogens; D004041:Dietary Fats; D019422:Dietary Sucrose; D007328:Insulin; D004052:Diethylnitrosamine