Protective role of plant sterol and stanol esters in liver inflammation: insights from mice and humans

PLoS One. 2014 Oct 30;9(10):e110758. doi: 10.1371/journal.pone.0110758. eCollection 2014.

Abstract

The inflammatory component of non-alcoholic steatohepatitis (NASH) can lead to irreversible liver damage. Therefore there is an urgent need to identify novel interventions to combat hepatic inflammation. In mice, omitting cholesterol from the diet reduced hepatic inflammation. Considering the effects of plant sterol/stanol esters on cholesterol metabolism, we hypothesized that plant sterol/stanol esters reduces hepatic inflammation. Indeed, adding plant sterol/stanol esters to a high-fat-diet reduced hepatic inflammation as indicated by immunohistochemical stainings and gene expression for inflammatory markers. Finally, adding sterol/stanol esters lowered hepatic concentrations of cholesterol precursors lathosterol and desmosterol in mice, which were highly elevated in the HFD group similarly as observed in severely obese patients with NASH. In vitro, in isolated LPS stimulated bone marrow derived macrophages desmosterol activated cholesterol efflux whereas sitostanol reduced inflammation. This highly interesting observation that plant sterol/stanol ester consumption leads to complete inhibition of HFD-induced liver inflammation opens new venues in the treatment and prevention of hepatic inflammation.

MeSH terms

  • Animals
  • Cholesterol / metabolism
  • Desmosterol / metabolism
  • Dietary Fats / adverse effects
  • Dietary Fats / pharmacology
  • Female
  • Humans
  • Inflammation / genetics
  • Inflammation / metabolism
  • Inflammation / pathology
  • Liver* / metabolism
  • Liver* / pathology
  • Macrophages* / metabolism
  • Macrophages* / pathology
  • Mice
  • Mice, Knockout
  • Non-alcoholic Fatty Liver Disease* / genetics
  • Non-alcoholic Fatty Liver Disease* / metabolism
  • Non-alcoholic Fatty Liver Disease* / pathology
  • Non-alcoholic Fatty Liver Disease* / prevention & control
  • Phytosterols / pharmacology*

Substances

  • Dietary Fats
  • Phytosterols
  • Desmosterol
  • lathosterol
  • Cholesterol

Grants and funding

The authors received no specific funding for this work.