Alisol B Alleviates Hepatocyte Lipid Accumulation and Lipotoxicity via Regulating RAR alpha-PPAR gamma-CD36 Cascade and Attenuates Non-Alcoholic Steatohepatitis in Mice

doi:10.3390/nu14122411

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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
	2022
发表期刊	NUTRIENTS
卷号	14 期号:12 页码:2411
摘要	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.
关键词	Alisol B non-alcoholic steatohepatitis RAR alpha CD36 FATTY LIVER HEPATIC STEATOSIS RECEPTOR ORIENTALE LIPOPROTEINS 23-ACETATE AGONIST CD36
DOI	10.3390/nu14122411
收录类别	SCI
WOS记录号	WOS:000818185300001
引用统计
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/74676
专题	中国科学院昆明植物研究所
推荐引用方式 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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