title: Protective role of plant sterol and stanol esters in liver inflammation: insights from mice and humans.
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.
authors.affiliation: Department of Human Biology, School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, the Netherlands.
authors.forename: Jogchum
authors.initials: J
authors.lastname: Plat
authors.affiliation: Department of Molecular Genetics, School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, the Netherlands.
authors.forename: Tim
authors.initials: T
authors.lastname: Hendrikx
authors.affiliation: Department of Molecular Genetics, School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, the Netherlands.
authors.forename: Veerle
authors.initials: V
authors.lastname: Bieghs
authors.affiliation: Department of Molecular Genetics, School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, the Netherlands.
authors.forename: Mike L J
authors.initials: ML
authors.lastname: Jeurissen
authors.affiliation: Department of Molecular Genetics, School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, the Netherlands.
authors.forename: Sofie M A
authors.initials: SM
authors.lastname: Walenbergh
authors.affiliation: Department of Molecular Genetics, School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, the Netherlands.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: van Gorp
authors.affiliation: Department of Human Biology, School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, the Netherlands.
authors.forename: Els
authors.initials: E
authors.lastname: De Smet
authors.affiliation: Department of Human Biology, School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, the Netherlands.
authors.forename: Maurice
authors.initials: M
authors.lastname: Konings
authors.affiliation: Department of Pediatrics, School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, the Netherlands.
authors.forename: Anita C E
authors.initials: AC
authors.lastname: Vreugdenhil
authors.affiliation: Department of Molecular Genetics, School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, the Netherlands.
authors.forename: Yasmin Dias
authors.initials: YD
authors.lastname: Guichot
authors.affiliation: Department of General Surgery, School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, the Netherlands.
authors.forename: Sander S
authors.initials: SS
authors.lastname: Rensen
authors.affiliation: Department of General Surgery, School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, the Netherlands.
authors.forename: Wim A
authors.initials: WA
authors.lastname: Buurman
authors.affiliation: Department of General Surgery, School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, the Netherlands; Atrium Medical Center Parkstad, Heerlen, the Netherlands.
authors.forename: Jan Willem M
authors.initials: JW
authors.lastname: Greve
authors.affiliation: Institute of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Bonn, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Lütjohann
authors.affiliation: Department of Human Biology, School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, the Netherlands.
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Mensink
authors.affiliation: Department of Molecular Genetics, School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, the Netherlands.
authors.forename: Ronit
authors.initials: R
authors.lastname: Shiri-Sverdlov
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D003897:Desmosterol / Q000378:metabolism; D004041:Dietary Fats / Q000009:adverse effects / Q000494:pharmacology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D010840:Phytosterols / Q000494:pharmacology*
chemical_list: D004041:Dietary Fats; D010840:Phytosterols; D003897:Desmosterol; C001521:lathosterol; D002784:Cholesterol