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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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Lipid Measurements.(A, B) Plasma and liver cholesterol measurements. (C, D) Plasma and liver triacylglycerol levels. (E) Scoring of liver slides for the accumulation of fat (steatosis) using HE staining. A score ranging from 0–3 (3 = highest steatosis) was given by an experienced pathologist. *P<0.05, **P<0.01, and ***P<0.001, respectively.
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pone-0110758-g004: Lipid Measurements.(A, B) Plasma and liver cholesterol measurements. (C, D) Plasma and liver triacylglycerol levels. (E) Scoring of liver slides for the accumulation of fat (steatosis) using HE staining. A score ranging from 0–3 (3 = highest steatosis) was given by an experienced pathologist. *P<0.05, **P<0.01, and ***P<0.001, respectively.

Mentions: As expected, we observed a strong increase in serum and hepatic cholesterol levels of mice fed an HFD as compared to the chow group. Compared to HFD alone, adding plant sterol or stanol esters to the HFD resulted in reduced serum and hepatic cholesterol concentrations to the levels found in controls (Figure 4A+B). As shown in the FPLC profiles (Figure 5A), the reductions in serum cholesterol can be found primarily in the VLDL and LDL fractions. Additionally, we found a reduction in serum TAG concentrations in animals receiving plant sterol and stanol esters enriched HFD (Figure 4C). Surprisingly, despite the effect of plant sterol and stanol esters on plasma TAG concentrations and VLDL particles (Figure 5B), liver TAG concentrations were not significantly different between the groups (Figure 4D).


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)

Lipid Measurements.(A, B) Plasma and liver cholesterol measurements. (C, D) Plasma and liver triacylglycerol levels. (E) Scoring of liver slides for the accumulation of fat (steatosis) using HE staining. A score ranging from 0–3 (3 = highest steatosis) was given by an experienced pathologist. *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-g004: Lipid Measurements.(A, B) Plasma and liver cholesterol measurements. (C, D) Plasma and liver triacylglycerol levels. (E) Scoring of liver slides for the accumulation of fat (steatosis) using HE staining. A score ranging from 0–3 (3 = highest steatosis) was given by an experienced pathologist. *P<0.05, **P<0.01, and ***P<0.001, respectively.
Mentions: As expected, we observed a strong increase in serum and hepatic cholesterol levels of mice fed an HFD as compared to the chow group. Compared to HFD alone, adding plant sterol or stanol esters to the HFD resulted in reduced serum and hepatic cholesterol concentrations to the levels found in controls (Figure 4A+B). As shown in the FPLC profiles (Figure 5A), the reductions in serum cholesterol can be found primarily in the VLDL and LDL fractions. Additionally, we found a reduction in serum TAG concentrations in animals receiving plant sterol and stanol esters enriched HFD (Figure 4C). Surprisingly, despite the effect of plant sterol and stanol esters on plasma TAG concentrations and VLDL particles (Figure 5B), liver TAG concentrations were not significantly different between the groups (Figure 4D).

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