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达帕格利弗洛辛通过减轻HFD养小鼠激活微质介导的下丘脑炎症来改善排卵障碍

Xiaolin Chen¹, Zhuoni Xiao², Qing Liu²

¹Department of Endocrinology, Renmin Hospital of Wuhan University, Wuhan, China.

Neuroendocrinology

|December 26, 2023

概括

像达帕格利弗洛辛这样的-葡萄糖共运输体2抑制剂 (SGLT2i) 可以改善因高脂肪饮食引起的排卵障碍. 这是通过调节葡萄糖代谢和减少大脑炎症来实现的,在肥胖中提供神经保护.

科学领域:

神经内分泌学神经内分泌学
代谢障碍代谢障碍代谢障碍
药理学药理学是指药理学的学科.

背景情况:

高脂肪饮食 (HFD) 诱导肥胖,并可能导致排卵障碍.
-葡萄糖共运输体2抑制剂 (SGLT2i) 已证明具有神经保护作用.
SGLT2i对HFD相关的排卵功能障碍的影响尚不清楚.

研究的目的:

调查达帕格利弗洛辛是否可以改善HFD诱导的排卵功能障碍.
为了确定达帕格利弗洛辛是否减轻了微质介导的下丘脑炎症.
探索涉及葡萄糖代谢和炎症的潜在机制.

主要方法:

雌性C57BL/6J小鼠被食HFD并接受22周的达帕格利弗洛辛治疗.
评估了代谢参数,激素水平和雌激素周期的规律性.
通过免疫光和免疫组织化学评估下丘脑微质激活,炎症标志物和神经递质表达.
研究了达帕格利弗洛辛对棕酸处理的HMC3细胞中的葡萄糖代谢和炎症因素的影响.

主要成果:

达帕格利弗洛辛改善了HFD诱导的代谢障碍,胰岛素/瘦素耐药性,并恢复了雌性周期.
达帕格利弗洛辛降低了微质细胞的激活,NLRP3炎症酶原始化和下丘脑炎症.
观察到GnRH和kisspeptin的下丘脑表达增加.
在体外,达帕格利弗洛辛降低了炎症因素,并抑制了mTOR/HK2介导的有氧糖解.

结论:

达帕格利弗洛辛通过通过mTOR/HK2信号调节葡萄糖代谢来改善与HFD相关的排卵障碍.
达帕格利弗洛辛减轻了微质介导的下丘脑炎症,显示出神经保护作用.
这些发现凸显了SGLT2抑制剂在管理与肥胖相关的生殖功能障碍方面的新作用.

关键词:

达帕格利弗洛辛 (Dapagliflozin) 是一种有高脂肪的饮食.下丘脑的下丘脑是什么意思炎症炎症是一种炎症.排卵排卵排卵排卵

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