Ginsenoside F1 administration promotes UCP1-dependent fat browning and ameliorates obesity-associated insulin resistance
Ginsenoside F1 administration promotes UCP1-dependent fat browning and ameliorates obesity-associated insulin resistance
复制标题
人参皂苷 F1 给药促进 UCP1 依赖性脂肪褐变并改善肥胖相关的胰岛素抵抗
DOI：
10.1016/j.fshw.2023.03.025
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发表时间：
2023-11-01
影响因子：
7
通讯作者：
Zhou，Yifa
中科院分区：
文献类型：
--
作者：
Meng，Yuhan;Li，Weili;Zhou，Yifa
肥胖引起的2型糖尿病主要是由于游离脂肪酸过多导致胰岛素抵抗。增加产热被认为是治疗低血脂和低血糖的有效策略。人参皂苷是人参中的一种天然活性成分。Meyer，其中一些增强产热作用。然而，关于黄芪皂甙促进产热的作用机制和作用靶点的研究还很少。利用产热蛋白解偶联蛋白1（UCP 1）-荧光素酶报告基因分析，我们确定了一个新的UCP 1激活剂的拟南芥皂甙库。通过pull down实验和抑制剂干扰实验，发现F1通过与β3-肾上腺素能受体（β3-AR）结合，通过cAMP/PKA/CREB途径增强UCP 1的表达。本实验还研究了F1对肥胖型糖尿病小鼠能量代谢的影响，包括体重、体成分和能量消耗。蛋白质组学结果表明，F1显著上调了产热蛋白和脂解蛋白，下调了脂肪酸合成蛋白。人参皂苷F1通过促进肥胖小鼠白色脂肪组织的布朗宁，增加产热，改善胰岛素抵抗。此外，BIF 1改善脂肪细胞和肝细胞中去甲肾上腺素诱导的胰岛素抵抗，并显示出比去甲肾上腺素更强的线粒体呼吸能力。这些结果表明，BMPF 1是一个有前途的先导化合物，在改善胰岛素抵抗。
Obesity-induced type 2 diabetes is mainly due to excessive free fatty acids leading to insulin resistance. Increasing thermogenesis is regarded as an effective strategy for hypolipidemia and hypoglycemia. Ginsenoside is a natural active component inPanax ginsengC.A. Meyer, and some of them enhance thermogenesis. However, there are few studies on the mechanism and target of ginsenosides enhancing thermogenesis. Using thermogenic protein uncoupling protein 1 (UCP1)-luciferase reporter assay, we identified ginsenoside F1 as a novel UCP1 activator in the ginsenosides library. Using pull down assay and inhibitor interference, we found F1 binds to β3-adrenergic receptors (β3-AR) to enhance UCP1 expression via cAMP/PKA/CREB pathway. We also investigated the ability of F1 on energy metabolism in obesity-induced diabetic mice, including body weight, body composition and energy expenditure. The results of proteomics showed that F1 significantly up-regulated thermogenesis proteins and lipolytic proteins, but down-regulated fatty acid synthesis proteins. Ginsenoside F1 increased thermogenesis and ameliorated insulin resistance specifically by promoting the browning of white adipose tissue in obese mice. Additionally, ginsenoside F1 improves norepinephrine-induced insulin resistance in adipocytes and hepatocytes, and shows a stronger mitochondria respiration ability than norepinephrine. These findings suggest that ginsenoside F1 is a promising lead compound in the improvement of insulin resistance.