High-salt in Addition to High-Fat Diet May Enhance Inflammation and Fibrosis in Liver Steatosis Induced by Oxidative Stress and Dyslipidemia in Mice

Lipids Health Dis. 2015 Feb 13;14:6. doi: 10.1186/s12944-015-0002-9.

Abstract

Background: It is widely known that salt is an accelerating factor for the progression of metabolic syndrome and causes cardiovascular diseases, most likely due to its pro-oxidant properties. We hypothesized that excessive salt intake also facilitates the development of nonalcoholic steatohepatitis (NASH), which is frequently associated with metabolic syndrome.

Methods: We examined the exacerbating effect of high-salt diet on high-fat diet-induced liver injury in a susceptible model to oxidative stress, apoE knockout and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) transgenic mice.

Results: High-salt diet led to NASH in high-fat diet-fed LOX-1 transgenic/apoE knockout mice without affecting high-fat diet-induced dyslipidemia or hepatic triglyceride accumulation. Additionally, a high-salt and high-fat diet stimulated oxidative stress production and inflammatory reaction to a greater extent than did a high-fat diet in the liver of LOX-1 transgenic/apoE knockout mice.

Conclusions: We demonstrated that high-salt diet exacerbated NASH in high-fat diet-fed LOX-1 transgenic /apoE knockout mice and that this effect was associated with the stimulation of oxidative and inflammatory processes; this is the first study to suggest the important role of excessive salt intake in the development of NASH.

MeSH terms

  • Animals
  • Blotting, Western
  • Diet, High-Fat / adverse effects*
  • Dyslipidemias / complications*
  • Dyslipidemias / pathology
  • Fatty Liver / etiology*
  • Fatty Liver / pathology
  • Fibrosis / etiology
  • Inflammation / etiology
  • Liver / chemistry
  • Liver / pathology
  • Male
  • Mice
  • Mice, Knockout
  • NADP / metabolism
  • Oxidative Stress / drug effects*
  • Oxidative Stress / physiology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Scavenger Receptors, Class E / biosynthesis
  • Scavenger Receptors, Class E / genetics
  • Sodium, Dietary / adverse effects*
  • Superoxides / analysis

Substances

  • Olr1 protein, mouse
  • Scavenger Receptors, Class E
  • Sodium, Dietary
  • Superoxides
  • NADP