Journal of Natural Medicines ( IF 2.5 ) Pub Date : 2022-09-17 , DOI: 10.1007/s11418-022-01647-w Li-Sha Ran 1 , Ya-Zeng Wu 1 , Yi-Wen Gan 1 , Hong-Lian Wang 2 , Li-Juan Wu 3 , Chun-Mei Zheng 3 , Yao Ming 3 , Ran Xiong 3 , Yong-Lin Li 3 , Shi-Hang Lei 3 , Xue Wang 3 , Xiao-Qing Lao 1 , Hong-Min Zhang 1 , Li Wang 2 , Chen Chen 4 , Chang-Ying Zhao 1, 3
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Abstract
Excessive intrahepatocellular lipid accumulation or steatosis is caused by abnormal lipid metabolism and a common character of nonalcoholic fatty liver disease (NAFLD), which may progress into cirrhosis and hepatocellular cancer. Andrographolide (Andro) is the primary active ingredient extracted from Andrographis paniculata, showing a protective role against dietary steatosis with the mechanism not fully understood. In this study, we showed that administration of Andro (50, 100, and 200 mg/kg/day for 8 weeks, respectively) attenuated obesity and metabolic syndrome in high-fat diet (HFD)-fed mice with improved glucose tolerance, insulin sensitivity, and reduced hyperinsulinemia, hyperglycemia, and hyperlipidemia. HFD-fed mice presented hepatic steatosis, which was significantly prevented by Andro. In vitro, Andro decreased the intracellular lipid droplets in oleic acid-treated LO2 cells. The selected RT-PCR array revealed a robust expression suppression of the fatty acid transport proteins (FATPs) by Andro treatment. Most importantly, we found that Andro consistently reduced the expression of FATP2 in both the oleic acid-treated LO2 cells and liver tissues of HFD-fed mice. Overexpression of FATP2 abolished the lipid-lowering effect of Andro in oleic acid-treated LO2 cells. Andro treatment also reduced the fatty acid uptake in oleic acid-treated LO2 cells, which was blunted by FATP2 overexpression. Collectively, our findings reveal a novel mechanism underlying the anti-steatosis effect of Andro by suppressing FATP2-mediated fatty acid uptake, suggesting the potential therapeutic application of Andro in the treatment of NAFLD.
Graphical abstract
中文翻译：
穿心莲内酯通过抑制非酒精性脂肪肝小鼠中 FATP2 介导的脂肪酸摄取来改善肝脏脂肪变性
抽象的
肝细胞内脂质过多堆积或脂肪变性是脂质代谢异常引起的，是非酒精性脂肪性肝病（NAFLD）的共同特征，可能进展为肝硬化和肝细胞癌。穿心莲内酯 (Andro) 是从穿心莲中提取的主要活性成分，对饮食性脂肪变性具有保护作用，但其机制尚不完全清楚。在这项研究中，我们表明，给予 Andro（分别为 50、100 和 200 mg/kg/天，持续 8 周）可减轻高脂饮食 (HFD) 喂养的小鼠的肥胖和代谢综合征，并改善葡萄糖耐量、胰岛素水平敏感性，并减少高胰岛素血症、高血糖和高脂血症。 HFD 喂养的小鼠出现肝脏脂肪变性，而 Andro 可以显着预防这种情况。在体外，Andro 减少了油酸处理的 LO2 细胞的细胞内脂滴。选定的 RT-PCR 阵列揭示了 Andro 处理对脂肪酸转运蛋白 (FATP) 的强烈表达抑制。最重要的是，我们发现 Andro 持续降低油酸处理的 LO2 细胞和 HFD 喂养小鼠肝组织中 FATP2 的表达。 FATP2 的过度表达消除了 Andro 在油酸处理的 LO2 细胞中的降脂作用。 Andro 处理还减少了油酸处理的 LO2 细胞中的脂肪酸摄取，而 FATP2 过度表达会减弱这种脂肪酸摄取。总的来说，我们的研究结果揭示了 Andro 通过抑制 FATP2 介导的脂肪酸摄取而发挥抗脂肪变性作用的新机制，表明 Andro 在 NAFLD 治疗中的潜在治疗应用。
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