Liou Chian-Jiun, Wu Shu-Ju, Shen Szu-Chuan, Chen Li-Chen, Chen Ya-Ling, Huang Wen-Chung
Department of Nursing, Division of Basic Medical Sciences, Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, No.261, Wenhua 1st Rd., Guishan Dist., Taoyuan City, 33303 Taiwan.
Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, Linkou, Guishan Dist., Taoyuan City, 33303 Taiwan.
Cell Biosci. 2020 Sep 29;10:114. doi: 10.1186/s13578-020-00477-1. eCollection 2020.
Phloretin is isolated from apple trees and could increase lipolysis in 3T3-L1 adipocytes. Previous studies have found that phloretin could prevent obesity in mice. In this study, we investigated whether phloretin ameliorates non-alcoholic fatty liver disease (NAFLD) in high-fat diet (HFD)-induced obese mice, and evaluated the regulation of lipid metabolism in hepatocytes.
HepG2 cells were treated with 0.5 mM oleic acid to induce lipid accumulation, and then treated with phloretin to evaluate the molecular mechanism of lipogenesis. In another experiment, male C57BL/6 mice were fed normal diet or HFD (60% fat, w/w) for 16 weeks. After the fourth week, mice were treated with or without phloretin by intraperitoneal injection for 12 weeks.
Phloretin significantly reduced excessive lipid accumulation and decreased sterol regulatory element-binding protein 1c, blocking the expression of fatty acid synthase in oleic acid-induced HepG2 cells. Phloretin increased Sirt1, and phosphorylation of AMP activated protein kinase to suppress acetyl-CoA carboxylase expression, reducing fatty acid synthesis in hepatocytes. Phloretin also reduced body weight and fat weight compared to untreated HFD-fed mice. Phloretin also reduced liver weight and liver lipid accumulation and improved hepatocyte steatosis in obese mice. In liver tissue from obese mice, phloretin suppressed transcription factors of lipogenesis and fatty acid synthase, and increased lipolysis and fatty acid β-oxidation. Furthermore, phloretin regulated serum leptin, adiponectin, triglyceride, low-density lipoprotein, and free fatty acid levels in obese mice.
These findings suggest that phloretin improves hepatic steatosis by regulating lipogenesis and the Sirt-1/AMPK pathway in the liver.
根皮素是从苹果树上分离出来的，可增加3T3-L1脂肪细胞中的脂肪分解。先前的研究发现根皮素可预防小鼠肥胖。在本研究中，我们调查了根皮素是否能改善高脂饮食（HFD）诱导的肥胖小鼠的非酒精性脂肪性肝病（NAFLD），并评估其对肝细胞脂质代谢的调节作用。
用0.5 mM油酸处理HepG2细胞以诱导脂质积累，然后用根皮素处理以评估脂肪生成的分子机制。在另一项实验中，雄性C57BL/6小鼠喂食正常饮食或HFD（60%脂肪，w/w）16周。第四周后，通过腹腔注射对小鼠进行有无根皮素的处理，持续12周。
根皮素显著减少了过量的脂质积累，并降低了固醇调节元件结合蛋白1c，阻断了油酸诱导的HepG2细胞中脂肪酸合酶的表达。根皮素增加了Sirt1以及AMP激活蛋白激酶的磷酸化，以抑制乙酰辅酶A羧化酶的表达，减少肝细胞中的脂肪酸合成。与未处理的HFD喂养小鼠相比，根皮素还降低了体重和脂肪重量。根皮素还减轻了肥胖小鼠的肝脏重量和肝脏脂质积累，并改善了肝细胞脂肪变性。在肥胖小鼠的肝脏组织中，根皮素抑制了脂肪生成的转录因子和脂肪酸合酶，并增加了脂肪分解和脂肪酸β氧化。此外，根皮素调节了肥胖小鼠的血清瘦素、脂联素、甘油三酯、低密度脂蛋白和游离脂肪酸水平。
这些发现表明，根皮素通过调节肝脏中的脂肪生成和Sirt-1/AMPK途径改善肝脂肪变性。
