State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China; International Joint Laboratory on Food Safety, Jiangnan University, Wuxi, Jiangsu 214122, China.
School of Science and Technology, Nottingham Trent University, Clifton, Nottingham NG11 8NS, United Kingdom.
Food Res Int. 2023 Jan;163:112198. doi: 10.1016/j.foodres.2022.112198. Epub 2022 Nov 19.
Lotus (Nelumbo nucifera Gaertn.) is an aquatic perennial crop planted worldwide and its leaf (also called "He-Ye") has therapeutic effects on obesity. However, whether the underlying mechanism leads to increased energy expenditure by activation of brown adipocytes has not been clarified. Here, murine CHT mesenchymal stem cells (MSCs) were employed to investigate the effects of ethanol extracts from lotus leaf (LLE) on brown adipocytes formation and the underlying molecular mechanisms. The results showed LLE was rich in polyphenols (383.7 mg/g) and flavonoids (178.3 mg/g), with quercetin 3-O-glucuronide (Q3G) the most abundant (128.2 μg/mg). In LLE-treated CHT MSCs, the expressions of lipolytic factors (e.g., ATGL, HSL, and ABHD5) and brown regulators (e.g., Sirt1, PGC-1α, Cidea, and UCP1) were significantly upregulated compared to that in the untreated MSCs. Furthermore, LLE promoted mitochondrial biogenesis and fatty acid β-oxidation, as evidenced by increases in the expression of Tfam, Cox7A, CoxIV, Cox2, Pparα, and Adrb3. Likewise, enhanced browning and mitochondrial biogenesis were also observed in Q3G-stimulated cells. Importantly, LLE and Q3G induced phosphorylation of AMPK accompanied by a remarkable increase in the brown fat marker UCP1, while pretreatment with Compound C (an AMPK inhibitor) reversed these changes. Moreover, stimulating LLE or Q3G-treated cells with CL316243 (a beta3-AR agonist) increased p-AMPKα/AMPKα ratio and UCP1 protein expression, indicating β3-AR/AMPK signaling may involve in this process. Collectively, these observations suggested that LLE, especially the component Q3G, stimulates thermogenesis by activating brown adipocytes, which may involve the β3-AR/AMPK signaling pathway.
荷花（Nelumbo nucifera Gaertn.）是一种水生多年生作物，在世界各地种植，其叶（也称为“荷叶”）对肥胖症具有治疗作用。然而，其潜在机制是否通过激活棕色脂肪细胞导致能量消耗增加尚不清楚。在这里，我们使用鼠类 CHT 间充质干细胞（MSCs）来研究荷叶（LLE）的乙醇提取物对棕色脂肪细胞形成的影响及其潜在的分子机制。结果表明，LLE 富含多酚（383.7 mg/g）和类黄酮（178.3 mg/g），其中槲皮素 3-O-葡萄糖醛酸苷（Q3G）含量最丰富（128.2 μg/mg）。在 LLE 处理的 CHT MSCs 中，与未处理的 MSCs 相比，脂肪分解因子（如 ATGL、HSL 和 ABHD5）和棕色调节因子（如 Sirt1、PGC-1α、Cidea 和 UCP1）的表达明显上调。此外，LLE 促进了线粒体生物发生和脂肪酸β氧化，表现为 Tfam、Cox7A、Cox4、Cox2、Pparα 和 Adrb3 的表达增加。同样，在 Q3G 刺激的细胞中也观察到了增强的棕色化和线粒体生物发生。重要的是，LLE 和 Q3G 诱导了 AMPK 的磷酸化，伴随着棕色脂肪标志物 UCP1 的显著增加，而用 Compound C（AMPK 抑制剂）预处理则逆转了这些变化。此外，用 CL316243（β3-AR 激动剂）刺激 LLE 或 Q3G 处理的细胞，增加了 p-AMPKα/AMPKα 比值和 UCP1 蛋白表达，表明β3-AR/AMPK 信号通路可能参与了这一过程。综上所述，这些结果表明，LLE，特别是其成分 Q3G，通过激活棕色脂肪细胞来刺激产热，这可能涉及β3-AR/AMPK 信号通路。
