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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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Hepatic gene expression.(A–E) Gene expression analysis of the macrophage marker Cd68, monocyte chemoattractant protein 1 (Mcp-1), interleukin 1β (IL-1β), tumor necrosis factor α (Tnf-α) and intercellular adhesion molecule 1 (Icam). Relative expression was normalized to endogenous control gene Cyclophilin A. Data were set relative to group on chow diet. n = 10 per group. *P<0.05, **P<0.01, and ***P<0.001, respectively.
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pone-0110758-g002: Hepatic gene expression.(A–E) Gene expression analysis of the macrophage marker Cd68, monocyte chemoattractant protein 1 (Mcp-1), interleukin 1β (IL-1β), tumor necrosis factor α (Tnf-α) and intercellular adhesion molecule 1 (Icam). Relative expression was normalized to endogenous control gene Cyclophilin A. Data were set relative to group on chow diet. n = 10 per group. *P<0.05, **P<0.01, and ***P<0.001, respectively.

Mentions: To further define the differences in hepatic inflammation, gene expression analysis of the pro-inflammatory markers Cd68, Mcp-1, IL-1β, Tnf-α and Icam was performed. Importantly, adding plant sterol or stanol esters to the HFD completely blocked the increase in hepatic expression of these inflammatory markers. For each of these inflammatory genes, the expression was significantly lowered in the plant sterol or stanol ester groups compared to the HFD alone and actually returned to values comparable to the chow condition (Figure 2A–E). Altogether, these data indicate the strong inhibitory effect of plant sterol or stanol esters on hepatic inflammation induced by HFD.


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)

Hepatic gene expression.(A–E) Gene expression analysis of the macrophage marker Cd68, monocyte chemoattractant protein 1 (Mcp-1), interleukin 1β (IL-1β), tumor necrosis factor α (Tnf-α) and intercellular adhesion molecule 1 (Icam). Relative expression was normalized to endogenous control gene Cyclophilin A. Data were set relative to group on chow diet. n = 10 per group. *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-g002: Hepatic gene expression.(A–E) Gene expression analysis of the macrophage marker Cd68, monocyte chemoattractant protein 1 (Mcp-1), interleukin 1β (IL-1β), tumor necrosis factor α (Tnf-α) and intercellular adhesion molecule 1 (Icam). Relative expression was normalized to endogenous control gene Cyclophilin A. Data were set relative to group on chow diet. n = 10 per group. *P<0.05, **P<0.01, and ***P<0.001, respectively.
Mentions: To further define the differences in hepatic inflammation, gene expression analysis of the pro-inflammatory markers Cd68, Mcp-1, IL-1β, Tnf-α and Icam was performed. Importantly, adding plant sterol or stanol esters to the HFD completely blocked the increase in hepatic expression of these inflammatory markers. For each of these inflammatory genes, the expression was significantly lowered in the plant sterol or stanol ester groups compared to the HFD alone and actually returned to values comparable to the chow condition (Figure 2A–E). Altogether, these data indicate the strong inhibitory effect of plant sterol or stanol esters on hepatic inflammation induced by HFD.

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