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

Plat J, Hendrikx T, Bieghs V, Jeurissen ML, Walenbergh SM, van Gorp PJ, De Smet E, Konings M, Vreugdenhil AC, Guichot YD, Rensen SS, Buurman WA, Greve JW, Lütjohann D, Mensink RP, Shiri-Sverdlov R - PLoS ONE (2014)

Bottom Line: 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.In vitro, in isolated LPS stimulated bone marrow derived macrophages desmosterol activated cholesterol efflux whereas sitostanol reduced inflammation.

View Article: PubMed Central - PubMed

Affiliation: Department of Human Biology, School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, the Netherlands.

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.

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Related in: MedlinePlus

Parameters of hepatic inflammation.(A, B) Liver sections were stained for infiltrating macrophages and neutrophils (Mac-1) and neutrophils (NIMP). From each liver, 6 random pictures were taken at 200x magnification to cover the whole slide. Positive cells for the specific staining were then counted being indicative for inflammation (C) Result of scoring for inflammation by an experienced pathologist using the HE staining in all groups. (D) Liver sections were stained for T-cells (CD3) and positive cells counted. (E, F) Representative pictures of Mac-1 staining and NIMP staining in the four experimental groups (200x magnification). *P<0.05, **P<0.01, and ***P<0.001, respectively.
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pone-0110758-g001: Parameters of hepatic inflammation.(A, B) Liver sections were stained for infiltrating macrophages and neutrophils (Mac-1) and neutrophils (NIMP). From each liver, 6 random pictures were taken at 200x magnification to cover the whole slide. Positive cells for the specific staining were then counted being indicative for inflammation (C) Result of scoring for inflammation by an experienced pathologist using the HE staining in all groups. (D) Liver sections were stained for T-cells (CD3) and positive cells counted. (E, F) Representative pictures of Mac-1 staining and NIMP staining in the four experimental groups (200x magnification). *P<0.05, **P<0.01, and ***P<0.001, respectively.

Mentions: To investigate the effect of plant sterol and stanol esters on hepatic inflammation, liver sections of mice that consumed the different diets were used for immunohistochemical stainings to detect the presence of infiltrated macrophages (Mac-1), neutrophils (NIMP), and T-lymphocytes (CD3) (Figure 1). In line with the reduced inflammation observed on the Hematoxylin and Eosin (HE) staining (Figure 1C), less infiltrating macrophages (Mac-1) and neutrophils (NIMP) were observed in the livers of mice receiving plant sterol or stanol esters compared to mice receiving only the HFD (Figures 1A+B). T-lymphocyte numbers were not significantly changed upon treatments with plant sterol or stanol esters (Figure 1D).


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

Plat J, Hendrikx T, Bieghs V, Jeurissen ML, Walenbergh SM, van Gorp PJ, De Smet E, Konings M, Vreugdenhil AC, Guichot YD, Rensen SS, Buurman WA, Greve JW, Lütjohann D, Mensink RP, Shiri-Sverdlov R - PLoS ONE (2014)

Parameters of hepatic inflammation.(A, B) Liver sections were stained for infiltrating macrophages and neutrophils (Mac-1) and neutrophils (NIMP). From each liver, 6 random pictures were taken at 200x magnification to cover the whole slide. Positive cells for the specific staining were then counted being indicative for inflammation (C) Result of scoring for inflammation by an experienced pathologist using the HE staining in all groups. (D) Liver sections were stained for T-cells (CD3) and positive cells counted. (E, F) Representative pictures of Mac-1 staining and NIMP staining in the four experimental groups (200x magnification). *P<0.05, **P<0.01, and ***P<0.001, respectively.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4214692&req=5

pone-0110758-g001: Parameters of hepatic inflammation.(A, B) Liver sections were stained for infiltrating macrophages and neutrophils (Mac-1) and neutrophils (NIMP). From each liver, 6 random pictures were taken at 200x magnification to cover the whole slide. Positive cells for the specific staining were then counted being indicative for inflammation (C) Result of scoring for inflammation by an experienced pathologist using the HE staining in all groups. (D) Liver sections were stained for T-cells (CD3) and positive cells counted. (E, F) Representative pictures of Mac-1 staining and NIMP staining in the four experimental groups (200x magnification). *P<0.05, **P<0.01, and ***P<0.001, respectively.
Mentions: To investigate the effect of plant sterol and stanol esters on hepatic inflammation, liver sections of mice that consumed the different diets were used for immunohistochemical stainings to detect the presence of infiltrated macrophages (Mac-1), neutrophils (NIMP), and T-lymphocytes (CD3) (Figure 1). In line with the reduced inflammation observed on the Hematoxylin and Eosin (HE) staining (Figure 1C), less infiltrating macrophages (Mac-1) and neutrophils (NIMP) were observed in the livers of mice receiving plant sterol or stanol esters compared to mice receiving only the HFD (Figures 1A+B). T-lymphocyte numbers were not significantly changed upon treatments with plant sterol or stanol esters (Figure 1D).

Bottom Line: 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.In vitro, in isolated LPS stimulated bone marrow derived macrophages desmosterol activated cholesterol efflux whereas sitostanol reduced inflammation.

View Article: PubMed Central - PubMed

Affiliation: Department of Human Biology, School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, the Netherlands.

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.

Show MeSH
Related in: MedlinePlus