Nobiletin protects against insulin resistance and disorders of lipid metabolism by reprogramming of circadian clock in hepatocytes

川陈皮素通过重新编程肝细胞中的昼夜节律来预防胰岛素抵抗和脂质代谢紊乱

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作者:Guoyuan Qi, Rui Guo, Haoyu Tian, Lixia Li, Hua Liu, Yashi Mi, Xuebo Liu

Conclusion

This study is the first to provide compelling evidences that NOB prevent cellular glucolipid metabolic imbalance and mitochondrial function in a Bmal1-dependent manner. Overall, NOB may serve as a nutritional preventive strategy in recovering metabolic disorders relevant to circadian clock.

Results

Our results revealed that NOB partially reverse the relatively shallow daily oscillations of circadian clock genes and reset phase-shifting circadian rhythms in primary hepatocytes under metabolic disorders conditions. Importantly, NOB was found to be effective at amplifying glucose uptake via stimulating IRS-1/AKT signaling pathway, as well as blunting palmitate-induced lipogenesis in HepG2 cells via modulating AMPK-Sirt1 signaling pathway and key enzymes of de novo lipogenesis in a Bmal1-dependent manner. NOB attenuated palmitate-stimulated excessive secretions of ROS, restored the depletions of mitochondrial membrane potential, which is similar to the recovery in expressions of mitochondrial respiration complex I-IV.

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