Effects of high fructose intake on liver injury progression in high fat diet induced fatty liver disease in ovariectomized female mice

Food Chem Toxicol. 2018 Aug;118:190-197. doi: 10.1016/j.fct.2018.05.006. Epub 2018 May 9.


Epidemiology shows that the morbidity of nonalcoholic fatty liver disease (NAFLD) is increased in postmenopausal women and chronic high fructose intake induces NAFLD progression. To analyze the effects of high fructose intake on estrogen deficiency, we evaluated liver disease progression using ovariectomized mice fed with a high fat diet (HFD) for 12 weeks. Hepatic steatosis developed in all HFD groups. Fructose intake significantly increased the liver weight and serum alanine aminotransferase, which was not exacerbated by ovariectomy alone. Ovariectomy enhanced the hepatic inflammatory activity shown by tumor necrosis factor α upregulation in the groups with or without fructose intake. Both fructose intake and ovariectomy increased the hepatocytes with ballooning degeneration and hepatic macrophage infiltration and activated hepatic stellate cells. Coexistence of fructose intake and ovariectomy markedly enhanced liver cell destruction, macrophage accumulation, and progression of fibrosis. Liver damage was ameliorated by 17β-estradiol supplementation. These findings suggest that high fructose intake enhanced the progression of NAFLD in ovariectomized female mice.

Keywords: Estrogen; Fructose; Hepatic steatosis; Menopause; Steatohepatitis.

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Chemical and Drug Induced Liver Injury / pathology*
  • Diet, High-Fat*
  • Disease Progression
  • Estradiol / administration & dosage
  • Female
  • Fructose / administration & dosage*
  • Liver / metabolism
  • Liver / pathology
  • Macrophages / metabolism
  • Mice, Inbred C57BL
  • Non-alcoholic Fatty Liver Disease / etiology*
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Non-alcoholic Fatty Liver Disease / pathology*
  • Ovariectomy*
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation


  • Tumor Necrosis Factor-alpha
  • Fructose
  • Estradiol
  • Alanine Transaminase