Antibiotics protect against fructose-induced hepatic lipid accumulation in mice: role of endotoxin

J Hepatol. 2008 Jun;48(6):983-92. doi: 10.1016/j.jhep.2008.01.035. Epub 2008 Mar 14.


Background/aims: Consumption of refined carbohydrates in soft drinks has been postulated to be a key factor in the development of non-alcoholic fatty liver disease (NAFLD). The aim of the present study was to test the effects of ad libitum access to different sugars consumed in drinking water on hepatic fat accumulation.

Methods: For 8 weeks, C57BL/J6 mice had free access to solutions containing 30% glucose, fructose, sucrose, or water sweetened with artificial sweetener (AS) or plain water. Body weight, caloric intake, hepatic steatosis and lipid peroxidation were assessed.

Results: Total caloric intake and weight gain were highest in mice exposed to glucose. In contrast, hepatic lipid accumulation was significantly higher in mice consuming fructose compared to all other groups. Moreover, endotoxin levels in portal blood and lipid peroxidation as well as TNFalpha expression were significantly higher in fructose fed mice than in all other groups. Concomitant treatment of fructose fed mice with antibiotics (e.g., polymyxin B and neomycin) markedly reduced hepatic lipid accumulation in fructose fed mice.

Conclusions: These data support the hypothesis that high fructose consumption may not only lead to liver damage through overfeeding but also may be directly pro-inflammatory by increasing intestinal translocation of endotoxin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use*
  • Body Weight / physiology
  • Disease Models, Animal
  • Eating / physiology
  • Endotoxins / metabolism*
  • Fatty Liver / etiology
  • Fatty Liver / metabolism
  • Fatty Liver / prevention & control*
  • Fructose / adverse effects*
  • Fructose / metabolism
  • I-kappa B Proteins / metabolism
  • Lipid Metabolism / drug effects*
  • Lipid Peroxidation / drug effects
  • Lipogenesis / drug effects
  • Lipogenesis / physiology
  • Liver / drug effects
  • Liver / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • NF-KappaB Inhibitor alpha
  • Neomycin / pharmacology
  • Neomycin / therapeutic use
  • Polymyxin B / pharmacology
  • Polymyxin B / therapeutic use


  • Anti-Bacterial Agents
  • Endotoxins
  • I-kappa B Proteins
  • Nfkbia protein, mouse
  • NF-KappaB Inhibitor alpha
  • Fructose
  • Neomycin
  • Polymyxin B