β-Sitosterol attenuates high-fat diet-induced intestinal inflammation in mice by inhibiting the binding of lipopolysaccharide to toll-like receptor 4 in the NF-κB pathway.

Abstract

SCOPE:

β-Sitosterol, a common phytosterol, has been shown to exhibit anti-inflammatory effects. Here, we investigated the effect of β-sitosterol on high-fat diet (HFD) induced colitis in mice and on LPS-stimulated mouse intestinal macrophages.

METHODS AND RESULTS:

C57BL/6J mice were maintained on an LFD (10 kcal% fat), an HFD (60 kcal% fat), or an HFD with β-sitosterol (20 mg/kg) administration for 8 weeks. The increased levels of body weight and epididymal fat pad weight as well as the concentrations of circulating proinflammatory cytokines and LPS in HFD mice compared with LFD mice were decreased by oral administration of β-sitosterol. The HFD-induced colonic inflammation evidenced by the increased expression of proinflammatory cytokines and the activation of nuclear factor kappa B (NF-κB) in the colon was also inhibited by β-sitosterol. In LPS-stimulated intestinal macrophages, β-sitosterol inhibited the production of proinflammatory cytokines and inflammatory enzymes as well as NF-κB activation. In addition, β-sitosterol significantly prevented the binding of LPS to intestinal as well as peritoneal macrophages. Furthermore, β-sitosterol potently inhibited the interaction between LPS and toll-like receptor 4 in intestinal macrophages transfected with control siRNA or MyD88 siRNA.

CONCLUSION:

These findings indicate that β-sitosterol ameliorates HFD-induced colitis by inhibiting the binding of LPS to toll-like receptor 4 in the NF-κB pathway.

• Authors: Kyung-Ah Kim, In-Ah Lee, Wan Gu, Supriya R Hyam, Dong-Hyun Kim
• Journal: Molecular nutrition & food research (Mol Nutr Food Res) Vol. 58 Issue 5 Pg. 963-72 (May 2014) ISSN: 1613-4133 [Electronic] Germany
• PMID: 24402767 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Cytokines
• Lipopolysaccharides
• Myd88 protein, mouse
• Myeloid Differentiation Factor 88
• NF-kappa B
• RNA, Small Interfering
• Sitosterols
• Tlr4 protein, mouse
• Toll-Like Receptor 4
• gamma-sitosterol

Topics

• Animals
• Colitis (chemically induced, drug therapy, pathology)
• Cytokines (antagonists & inhibitors, metabolism)
• Diet, High-Fat (adverse effects)
• Inflammation (drug therapy, pathology)
• Intestines (drug effects, pathology)
• Lipopolysaccharides (metabolism)
• Macrophages, Peritoneal (drug effects, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Inbred ICR
• Myeloid Differentiation Factor 88 (genetics, metabolism)
• NF-kappa B (antagonists & inhibitors, genetics, metabolism)
• RNA, Small Interfering (genetics, metabolism)
• Signal Transduction
• Sitosterols (pharmacology)
• Toll-Like Receptor 4 (genetics, metabolism)