Quercetin 3-O-glucuronide-rich lotus leaf extract promotes a Brown-fat-phenotype in C3H10T1/2 mesenchymal stem cells

安普克 产热 线粒体生物发生 化学 槲皮素 PRDM16 产热素 间充质干细胞 细胞生物学 生物化学 褐色脂肪组织 生物 脂肪组织 磷酸化 线粒体 蛋白激酶A 抗氧化剂
作者
Zhenyu Wang,Chaoyi Xue,Xuan Wang,Maomao Zeng,Zhaojun Wang,Qiuming Chen,Jie Chen,Mark Christian,Zhiyong He
出处
期刊:Food Research International [Elsevier BV]
卷期号:163: 112198-112198 被引量:9
标识
DOI:10.1016/j.foodres.2022.112198
摘要

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 C3H10T1/2 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 C3H10T1/2 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.
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