Geniposide Improves Glucose Homeostasis via Regulating FoxO1/PDK4 in Skeletal Muscle
Geniposide Improves Glucose Homeostasis via Regulating FoxO1/PDK4 in Skeletal Muscle
复制标题
京尼平苷通过调节骨骼肌中的 FoxO1/PDK4 改善血糖稳态
DOI：
10.1021/acs.jafc.9b00402
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发表时间：
2019-04-24
影响因子：
6.1
通讯作者：
Ying, Hao
中科院分区：
文献类型：
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作者：
Li, Yan;Pan, Haiou;Ying, Hao
众所周知，葡萄糖代谢失衡状态会引发许多代谢性疾病，骨骼肌对葡萄糖的摄取占体重的90%。京尼平苷是栀子果实中的主要天然活性成分之一，其对骨骼肌糖代谢的调节作用尚未见报道。在此，基于微阵列分析，我们发现京尼平苷降低小鼠骨骼肌中丙酮酸脱氢酶激酶4（PDK 4）的表达，随后发现京尼平苷在体外和体内抑制叉头盒O 1（FoxO 1）、PDK 4和磷酸化丙酮酸脱氢酶的表达。此外，京尼平苷促进了慢肌纤维类型和葡萄糖利用的快速转换，表明京尼平苷改善了葡萄糖稳态。此外，机理研究表明，京尼平苷通过调节FoxO 1/PDK 4发挥上述作用，FoxO 1/PDK 4通过丙酮酸脱氢酶控制燃料选择。同时，过表达FoxO 1可逆转京尼平苷的上述作用。总之，这些结果表明，京尼平苷通过骨骼肌中的FoxO 1/PDK 4控制燃料使用和葡萄糖稳态。
It is well-known that imbalance state of glucose metabolism triggers many metabolic diseases and glucose uptake in skeletal muscle accounts for 90% of body weight. Geniposide is one of the major natural bioactive constituents of gardenia fruit, and the regulation of geniposide on glucose metabolism in skeletal muscle has not yet been investigated. Here, on the basis of microarray analysis, we discovered that geinposide decreased pyruvate dehydrogenase kinase 4 (PDK4) expression in skeletal muscle of mice and subsequently found that geniposide inhibited the expressions of forkhead box O1 (FoxO1), PDK4, and phosphorylated pyruvate dehydrogenase in vitro and in vivo. Moreover, geniposide promoted a switch of slow-to-fast myofiber type and glucose utilization, suggesting that geniposide improved glucose homeostasis. In addition, mechanistic studies revealed that geniposide played above roles by regulating FoxO1/PDK4, which controlled fuel selection via pyruvate dehydrogenase. Meanwhile, effects of geniposide mentioned above could be reversed by FoxO1 overexpression. Together, these results establish that geniposide confers controls on fuel usage and glucose homeostasis through FoxO1/PDK4 in skeletal muscle.