Catalpol Attenuates Hepatic Steatosis by Regulating Lipid Metabolism via AMP-Activated Protein Kinase Activation
Catalpol Attenuates Hepatic Steatosis by Regulating Lipid Metabolism via AMP-Activated Protein Kinase Activation
复制标题
梓醇通过 AMP 激活的蛋白激酶激活调节脂质代谢，从而减轻肝脏脂肪变性
DOI：
10.1155/2020/6708061
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发表时间：
2020-04-27
影响因子：
--
通讯作者：
Chen, Yong
中科院分区：
文献类型：
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作者：
Tian, Xiang;Ru, Qin;Chen, Yong
非酒精性脂肪性肝病（NAFLD）的患病率增加，由肝脏脂肪变性发展而来，代表了公共卫生挑战。梓醇是一种从中药葛根中提取的天然成分，具有多种药理活性。本研究旨在通过细胞实验和动物实验研究梓醇是否能预防肝脂肪变性，并阐明其可能的机制。在体外用300 μM棕榈酸酯（PA）和/或梓醇处理HepG 2细胞24 h，并在体内给予喂食高脂饮食（HFD）的雄性C57 BL/6 J小鼠18周梓醇。结果表明，梓醇显着降低PA处理的HepG 2细胞中的脂质积累。此外，梓醇显著降低体重和肝脏中的脂质积累，而它改善了HFD喂养小鼠的肝细胞脂肪变性。值得注意的是，梓醇显着促进磷酸化的AMP激活的蛋白激酶（AMPK）和乙酰辅酶A羧化酶。随后，梓醇抑制脂肪生成相关基因的表达，如固醇调节元件结合蛋白1c和脂肪酸合成酶，但促进与脂肪酸β-氧化相关的基因的表达，如过氧化物酶体增殖物激活受体α及其靶基因肉毒碱棕榈酰转移酶1和酰基辅酶A氧化酶1（ACOX 1）。然而，HepG 2细胞与AMPK抑制剂化合物C（10 μM）预孵育，阻止了梓醇介导的有益作用。这些发现表明梓醇通过以AMPK依赖性方式抑制脂肪生成和增强脂肪酸β-氧化来改善肝脂肪变性。因此，梓醇具有作为治疗NAFLD的新药物的潜力。
The increased prevalence of nonalcoholic fatty liver disease (NAFLD), which develops from hepatic steatosis, represents a public health challenge. Catalpol, a natural component extracted from the roots of Radix Rehmanniae, has several pharmacological activities. The present study is aimed at examining whether catalpol prevents hepatic steatosis in cell and animal experiments and elucidating the possible mechanisms. HepG2 cells were treated with 300 μM palmitate (PA) and/or catalpol for 24 h in vitro, and male C57BL/6J mice fed a high-fat diet (HFD) were administered catalpol for 18 weeks in vivo. The results revealed that catalpol significantly decreased lipid accumulation in PA-treated HepG2 cells. Moreover, catalpol drastically reduced body weight and lipid accumulation in the liver, whereas it ameliorated hepatocyte steatosis in HFD-fed mice. Notably, catalpol remarkably promoted the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase. Subsequently, catalpol repressed the expressions of lipogenesis-associated genes such as sterol regulatory element-binding protein 1c and fatty acid synthase but promoted the expressions of genes associated with fatty acid β-oxidation such as peroxisome proliferator-activated receptor α together with its target genes carnitine palmitoyltransferase 1 and acyl-CoA oxidase 1 (ACOX1). However, the preincubation of the HepG2 cells with compound C (10 μM), an AMPK inhibitor, prevented catalpol-mediated beneficial effects. These findings suggest that catalpol ameliorates hepatic steatosis by suppressing lipogenesis and enhancing fatty acid β-oxidation in an AMPK-dependent manner. Therefore, catalpol has potential as a novel agent in the treatment of NAFLD.