Foxo1在肥胖相关下丘脑炎症中的作用及其机制

The role and mechanism of Foxo1 in obesity-related hypothalamus inflammation

摘要:

下丘脑是调节食物摄入和能量平衡的关键器官，在肥胖发生中起着决定性作用。下丘脑炎症可导致下丘脑的瘦素和胰岛素抵抗，以及控制能量稳态的信号通路受损，可能是能量调控失衡和肥胖发生的始作俑者。Foxo1作为重要的核转录因子，在下丘脑弓状核AgRP和POMC神经元中广泛表达，并在下丘脑炎症及中枢胰岛素抵抗中起关键作用，具体分子机制未明。可以推论，下丘脑Foxo1的调控是能量平衡的关键调节因子，可能是肥胖治疗的新的潜在靶点。本文综述了Foxo1和下丘脑炎症之间的关系及其在肥胖发生发展中的作用。

Abstract:

The hypothalamus is an important organ for controlling food intake and energy balance, which is critical for the obesity development. Hypothalamic inflammation can result in hypothalamic leptin and insulin resistance, as well as impair signaling pathways that regulate energy homeostasis, which may be the initiator of energy regulation imbalance and obesity. Foxo1 is a nuclear transcription factor expressed abundantly in AgRP and POMC neurons in the hypothalamic arcuate nucleus and has a critical role in hypothalamic inflammation and central insulin resistance；however, its molecular mechanism is still unknown. It is suggested that Foxo1 might be a key regulator of energy balance in the hypothalamus and it would be a novel therapeutic target for obesity. This review summarizes the relationship between Foxo1 and hypothalamic inflammation, as well as its role in the occurrence and progression of obesity.