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| Alisol B Alleviates Hepatocyte Lipid Accumulation and Lipotoxicity via Regulating RAR alpha-PPAR gamma-CD36 Cascade and Attenuates Non-Alcoholic Steatohepatitis in Mice | |
Zhao, Zhuohui; Deng, Zhen-Tao; Huang, Suling; Ning, Mengmeng; Feng, Ying; Shen, Yu; Zhao, Qin-Shi ; Leng, Ying
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| 2022 | |
| Source Publication | NUTRIENTS
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| Volume | 14Issue:12Pages:2411 |
| Abstract | Non-alcoholic steatohepatitis (NASH) is a common chronic liver disease worldwide, with no effective therapies available. Discovering lead compounds from herb medicine might be a valuable strategy for the treatment of NASH. Here, we discovered Alisol B, a natural compound isolated from Alisma orientalis (Sam.), that attenuated hepatic steatosis, inflammation, and fibrosis in high-fat diet plus carbon tetrachloride (DIO+CCl4)-induced and choline-deficient and amino acid-defined (CDA)-diet-induced NASH mice. RNA-seq showed Alisol B significantly suppressed CD36 expression and regulated retinol metabolism in NASH mice. In mouse primary hepatocytes, Alisol B decreased palmitate-induced lipid accumulation and lipotoxicity, which were dependent on CD36 suppression. Further study revealed that Alisol B enhanced the gene expression of RAR alpha with no direct RAR alpha agonistic activity. The upregulation of RAR alpha by Alisol B reduced HNF4 alpha and PPAR gamma expression and further decreased CD36 expression. This effect was fully abrogated after RAR alpha knockdown, suggesting Alisol B suppressed CD36 via regulating RAR alpha-HNF4 alpha-PPAR gamma cascade. Moreover, the hepatic gene expression of RAR alpha was obviously decreased in murine NASH models, whereas Alisol B significantly increased RAR alpha expression and decreased CD36 expression, along with the downregulation of HNF4 alpha and PPAR gamma. Therefore, this study showed the unrecognized therapeutic effects of Alisol B against NASH with a novel mechanism by regulating RAR alpha-PPAR gamma-CD36 cascade and highlighted Alisol B as a promising lead compound for the treatment of NASH. |
| Keyword | Alisol B non-alcoholic steatohepatitis RAR alpha CD36 FATTY LIVER HEPATIC STEATOSIS RECEPTOR ORIENTALE LIPOPROTEINS 23-ACETATE AGONIST CD36 |
| DOI | 10.3390/nu14122411 |
| Indexed By | SCI |
| WOS ID | WOS:000818185300001 |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | http://ir.kib.ac.cn/handle/151853/74676 |
| Collection | 中国科学院昆明植物研究所 |
| Recommended Citation GB/T 7714 | Zhao, Zhuohui,Deng, Zhen-Tao,Huang, Suling,et al. Alisol B Alleviates Hepatocyte Lipid Accumulation and Lipotoxicity via Regulating RAR alpha-PPAR gamma-CD36 Cascade and Attenuates Non-Alcoholic Steatohepatitis in Mice[J]. NUTRIENTS,2022,14(12):2411. |
| APA | Zhao, Zhuohui.,Deng, Zhen-Tao.,Huang, Suling.,Ning, Mengmeng.,Feng, Ying.,...&Leng, Ying.(2022).Alisol B Alleviates Hepatocyte Lipid Accumulation and Lipotoxicity via Regulating RAR alpha-PPAR gamma-CD36 Cascade and Attenuates Non-Alcoholic Steatohepatitis in Mice.NUTRIENTS,14(12),2411. |
| MLA | Zhao, Zhuohui,et al."Alisol B Alleviates Hepatocyte Lipid Accumulation and Lipotoxicity via Regulating RAR alpha-PPAR gamma-CD36 Cascade and Attenuates Non-Alcoholic Steatohepatitis in Mice".NUTRIENTS 14.12(2022):2411. |
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| ARTN 2411.pdf（6451KB） | 期刊论文 | 出版稿 | 开放获取 | CC BY-NC-SA | View Download | |
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