Non‐alcoholic fatty liver disease is a public health problem worldwide associated with high morbidity and hepatic steatosis, but no effective therapeutic interventions. Magnesium isoglycyrrhizinate (MGIG), a derivative of an active component of Glycyrrhiza glabra , is widely used for the treatment of inflammatory liver diseases due to its potent anti‐inflammatory and hepatoprotective activities. Hence, this study aimed to study the effects of MGIG on hepatic steatosis in mice fed a high‐fat diet (HFD). Oil Red O staining and transmission electron microscopy revealed a decrease in lipid accumulation in the liver after MGIG treatment along with improved mitochondrial ultramicrostructures. Metabonomic analysis demonstrated that MGIG intervention increased glutamate utilization in mitochondria by promoting the uptake of glutamate into the tricarboxylic acid (TCA) cycle. The NAD⁺/NADH ratio and the expression of other lipid‐metabolism‐related genes were increased in MGIG‐treated livers. Transcriptome sequencing showed that the expression of TLR4, an isoform of the innate immunity Toll‐like receptors (TLRs), was significantly decreased after MGIG treatment, suggesting a link between the anti‐inflammatory effects of MGIG and its suppression of lipidation. Our results reveal the potent effects of MGIG on lipid metabolism and suggest that hepatic TLR4 might be a crucial therapeutic target to regulate energy homeostasis in hepatic steatosis.

中文翻译：

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异甘草酸镁可通过调节能量稳态来预防非酒精性肝脂肪变性。

非酒精性脂肪肝是世界范围内与高发病率和肝脂肪变性相关的公共卫生问题，但尚无有效的治疗干预措施。异甘草酸镁（MGIG），甘草有效成分的衍生物由于其有效的抗炎和保肝活性，被广泛用于治疗炎症性肝病。因此，本研究旨在研究MGIG对高脂饮食（HFD）喂养的小鼠肝脂肪变性的影响。油红O染色和透射电镜显示MGIG治疗后肝脏脂质堆积减少，线粒体超微结构得到改善。代谢组学分析表明，MGIG干预可通过促进谷氨酸向三羧酸（TCA）循环的吸收来增加线粒体中谷氨酸的利用。NAD ⁺MGIG治疗的肝脏中，/ NADH比率和其他脂质代谢相关基因的表达增加。转录组测序显示，MGIG治疗后TLR4（先天免疫Toll样受体（TLRs）的同种型）的表达显着降低，表明MGIG的抗炎作用与其抑制脂化之间存在联系。我们的研究结果揭示了MGIG对脂质代谢的有效作用，并提示肝TLR4可能是调节肝脂肪变性能量稳态的关键治疗靶标。