Benzyl isothiocyanate ameliorates high-fat/cholesterol/cholic acid diet-induced nonalcoholic steatohepatitis through inhibiting cholesterol crystal activated NLRP3 inflammasome in Kupffer cells
NLR: Nucleotide-binding domain and leucine-rich repeat-containing (NLR) inflammasomes
NLRP3: NLR family pyrin domain-containing protein 3
Activation of the NLRP3 inflammasome is found to be responsible for the development of diet-induced nonalcoholic steatohepatitis (NASH). Benzyl isothiocyanate (BITC) is rich in cruciferous vegetables such as garden cress, turnip, and papaya, and it assists several biological activities including anti-cancer, anti-oxidative, anti-inflammatory, and anti-microbes. However, less knowledge is available to clarify whether BITC improves high-fat diet-induced NASH and the role of NLRP3 inflammasome in developing NASH. Chen and colleagues (2020) published a study titled “Benzyl isothiocyanate ameliorates high-fat/cholesterol/cholic acid diet-induced nonalcoholic steatohepatitis through inhibiting cholesterol crystal activated NLRP3 inflammasome in Kupffer cells” in the National Library of Medicine. The summary of this study is provided below:
Objective:
To evaluate whether benzyl isothiocyanate (BITC) improves diet-induced NASH and the mechanisms involved.
Method:
Male 6-week-old C57BL/6 J mice fed a high-fat diet containing cholesterol and cholic acid (HFCCD) for 9 weeks. Kupffer cells were stimulated with LPS, and cholesterol crystals (CC) were investigated.
Findings:
Studies suggest that BITC has a chemopreventive role in NAFLD development. BITC was found to effectively improve the development of steatohepatitis by inhibiting NLRP3 inflammasome-driven IL-1β production in Kupffer cells. Observations also add that CC activation of NLRP3 inflammasome is associated with HFCCD-induced steatohepatitis. While there was no difference observed in epididymal fat weight after HFCCD for 9 weeks, it was also found that there is a significant decrease in body weight of the BITC group as compared to the normal diet (ND) group.
This study strongly recommended that targeting NLRP3 inflammasome in Kupffer cells can be a promising approach to improve NASH.
This study also highlights that hepatic caspase 3 activation in the HFCCD-fed mice highly associated with the increase in caspase 1 activity, and change in caspase 3 activity was reduced by BITC. This explains the anti-apoptotic activity of BITC in protecting NASH development.
Limitation:
The author acknowledges that the mechanism by which BITC reduces liver steatosis was not researched in this study. Also, future studies to investigate whether post-translational modification of NLRP3 inflammasome participates in BITC termination of diet-induced steatohepatitis.
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