A novel small compound TOIDC suppresses lipogenesis via SREBP1-dependent signaling to curb MAFLD.
A novel small compound TOIDC suppresses lipogenesis via SREBP1-dependent signaling to curb MAFLD.
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DOI：
10.1186/s12986-022-00713-0
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发表时间：
2022-12-06
影响因子：
4.5
通讯作者：
Liu, Junli
中科院分区：
文献类型：
--
作者：
Shao, Yaodi;Yao, Zhi;Zhou, Junyi;Yu, Miao;Chen, Suzhen;Yuan, Yanmei;Han, Liu;Jiang, Liqin;Liu, Junli
关键词：
抑制肝脏脂肪生成被广泛认为是代谢相关脂肪肝（MAFLD）的有效治疗方法，尽管许多相关药物未能达到临床应用。这项研究的目的是确定一种新的小化合物，可以有效地治疗MAFLD。首先将原代肝细胞暴露于棕榈酸和油酸，然后在高通过筛选细胞脂质含量之前用化合物处理。通过尼罗红染色和甘油三酯分析来测量这些化合物的功效。通过CCK-8测定法评价了这些化合物引起的潜在细胞毒性。qPCR和Western印迹分别用于确定RNA和蛋白质的表达。将该化合物腹膜内注射到饮食诱导的肥胖（DIO）小鼠中以检查其体内功效。我们确定1-甲基-2-硫代吲哚啉-3，3-二羧酸二甲酯（TOIDC）是一种有效的化学物质，可降低细胞脂质，细胞毒性最小。当腹膜内注射时，TOIDC有效地改善DIO小鼠中的MAFLD。TOIDC通过抑制固醇调节元件结合蛋白1（SREBP 1），在机制上抑制从头脂肪生成。我们的研究结果表明，TOIDC可能是一个有前途的先导化合物，开发新的药物来治疗MAFLD。在线版本包含补充材料，可通过10.1186/s12986-022-00713-0获取。
Inhibition of hepatic lipogenesis is widely regarded as an effective treatment for metabolic-associated fatty liver disease (MAFLD), although numerous related drugs have failed to reach clinical application. The goal of this study is to identify a novel small compound that can effectively treat MAFLD. Primary hepatocytes were first exposed to palmitic acid and oleic acid, then treated with compounds prior to high through screening for cellular lipid content. The efficacy of these compounds was measured by Nile Red staining and triglyceride analysis. The potential cellular toxicity caused by these compounds was evaluated by CCK8 assay. qPCR and Western blot were used to determine expression of RNAs and proteins, respectively. The compound was intraperitoneally injected into diet-induced obese (DIO) mice to examine its efficacy in vivo. We identified the dimethyl 1-methyl-2-thioxoindoline-3,3-dicarboxylate (TOIDC) as a powerful chemical to reduce cellular lipid with minimal cellular toxicity. When injected intraperitoneally, TOIDC effectively ameliorates MAFLD in DIO mice. Mechanically, TOIDC suppresses de novo lipogenesis through inhibiting sterol regulatory element-binding protein 1 (SREBP1). Our findings indicate that TOIDC could be a promising lead compound to develop new drugs to treat MAFLD. The online version contains supplementary material available at 10.1186/s12986-022-00713-0.
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影响因子：
29.4
作者：
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