Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Nutrients. 2022 Apr 30;14(9):1898. doi: 10.3390/nu14091898.
Nuciferine (Nuci), the main aporphine alkaloid component in lotus leaf, was reported to reduce lipid accumulation in vitro. Herein we investigated whether Nuci prevents obesity in high fat diet (HFD)-fed mice and the underlying mechanism in liver/HepG2 hepatocytes and epididymal white adipose tissue (eWAT) /adipocytes. Male C57BL/6J mice were fed with HFD supplemented with Nuci (0.10%) for 12 weeks. We found that Nuci significantly reduced body weight and fat mass, improved glycolipid profiles, and enhanced energy expenditure in HFD-fed mice. Nuci also ameliorated hepatic steatosis and decreased the size of adipocytes. Furthermore, Nuci remarkably promoted the phosphorylation of AMPK, suppressed lipogenesis (SREBP1, FAS, ACC), promoted lipolysis (HSL, ATGL), and increased the expressions of adipokines (FGF21, ZAG) in liver and eWAT. Besides, fatty acid oxidation in liver and thermogenesis in eWAT were also activated by Nuci. Similar results were further observed at cellular level, and these beneficial effects of Nuci in cells were abolished by an effective AMPK inhibitor compound C. In conclusion, Nuci supplementation prevented HFD-induced obesity, attenuated hepatic steatosis, and reduced lipid accumulation in liver/hepatocytes and eWAT/adipocytes through regulating AMPK-mediated FAS/HSL pathway. Our findings provide novel insight into the clinical application of Nuci in treating obesity and related complications.
荷叶中的主要阿朴啡类生物碱成分荷叶碱（Nuci）已被报道可减少体外脂质积累。在此，我们研究了 Nuci 是否可预防高脂饮食（HFD）喂养小鼠的肥胖及其在肝脏/HepG2 肝细胞和附睾白色脂肪组织（eWAT）/脂肪细胞中的潜在机制。雄性 C57BL/6J 小鼠喂食 HFD 并补充 0.10%的 Nuci 共 12 周。结果发现，Nuci 可显著降低 HFD 喂养小鼠的体重和脂肪量，改善糖脂谱，并增强其能量消耗。Nuci 还可改善肝脂肪变性并减少脂肪细胞的大小。此外，Nuci 可显著促进 AMPK 的磷酸化，抑制脂肪生成（SREBP1、FAS、ACC），促进脂肪分解（HSL、ATGL），并增加肝脏和 eWAT 中脂肪因子（FGF21、ZAG）的表达。此外，Nuci 还可激活肝脏中的脂肪酸氧化和 eWAT 中的产热作用。在细胞水平上也观察到了类似的结果，而 AMPK 有效抑制剂化合物 C 可消除 Nuci 在细胞中的这些有益作用。总之，Nuci 补充可预防 HFD 诱导的肥胖，减轻肝脏脂肪变性，并通过调节 AMPK 介导的 FAS/HSL 通路减少肝脏/肝细胞和 eWAT/脂肪细胞中的脂质积累。我们的研究结果为 Nuci 在治疗肥胖及相关并发症中的临床应用提供了新的见解。
