Phloretin 通过调节肥胖小鼠的脂肪生成和 Sirt1/AMPK 信号传导改善肝脏脂肪变性,Cell and Bioscience

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Phloretin 通过调节肥胖小鼠的脂肪生成和 Sirt1/AMPK 信号传导改善肝脏脂肪变性
Cell and Bioscience ( IF 6.1 ) Pub Date : 2020-09-29 , DOI: 10.1186/s13578-020-00477-1
Chian-Jiun Liou , Shu-Ju Wu , Szu-Chuan Shen , Li-Chen Chen , Ya-Ling Chen , Wen-Chung Huang

Phloretin 从苹果树中分离出来，可以增加 3T3-L1 脂肪细胞的脂肪分解。先前的研究发现，根皮素可以预防小鼠肥胖。在本研究中，我们研究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肝病 (NAFLD)，并评估肝细胞中脂质代谢的调节。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 小鼠被喂食正常饮食或 HFD（60% 脂肪，w/w）16 周。第四周后，通过腹膜内注射用或不用根皮素对小鼠进行治疗 12 周。Phloretin 显着减少过多的脂质积累并降低甾醇调节元件结合蛋白 1c，从而阻断油酸诱导的 HepG2 细胞中脂肪酸合酶的表达。Phloretin 增加了 Sirt1，并且 AMP 的磷酸化激活了蛋白激酶以抑制乙酰辅酶 A 羧化酶的表达，从而减少肝细胞中的脂肪酸合成。与未经治疗的 HFD 喂养小鼠相比，根皮素还降低了体重和脂肪重量。Phloretin 还降低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。在肥胖小鼠的肝组织中，根皮素抑制了脂肪生成和脂肪酸合酶的转录因子，并增加了脂肪分解和脂肪酸 β-氧化。此外，根皮素调节血清瘦素、脂联素、甘油三酯、低密度脂蛋白、和肥胖小鼠的游离脂肪酸水平。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 通路来改善肝脏脂肪变性。

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Phloretin ameliorates hepatic steatosis through regulation of lipogenesis and Sirt1/AMPK signaling in obese mice

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.

更新日期：2020-09-30

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