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在衰老过程中由canagliflozin进行的下丘脑性别特异性代谢转变

Hashan S M Jayarathne¹, Ryan Sullivan¹, Lukas Stilgenbauer¹

¹Department of Biological Sciences, Integrative Biosciences Center, Wayne State University, Room 2418 IBio, 6135 Woodward, Detroit, MI, 48202, USA.

|May 27, 2024

概括

在衰老的雄性和雌性小鼠中,卡纳格里弗洛辛 (Cana) 对下丘脑代谢控制的影响不同. 长期治疗改善了代谢率和神经保护,男性对代谢途径表现出更持久的影响.

科学领域:

神经科学是一个神经科学.
代谢过程中的代谢.
内分泌学在内分泌学.

背景情况:

下丘脑调节新陈代谢和随着衰老而发生的变化.
像Canagliflozin (Cana) 这样的-葡萄糖共载体2抑制剂 (SGLT2i) 改善了代谢平衡.
卡纳已经显示出在延长寿命和改善老年雄性小鼠的代谢控制方面的潜力.

研究的目的:

调查Cana对老化UM-HET3小鼠下丘脑代谢控制的长期和短期影响.
为了确定下丘脑中对Cana治疗的性别特异性反应.
为了确定Cana对衰老代谢的影响背后的分子机制.

主要方法:

从7个月大开始,对UM-HET3小鼠给予Cana.
评估体重,脂肪量,耐葡萄糖和胰岛素敏感性.
间接热量计用于测量能源消耗.
通过RNA测序对下丘脑基因表达的分析.

主要成果:

短期Cana治疗减少了男性的体重和脂肪量,提高了12个月的葡萄糖耐受性和胰岛素敏感性.
在12个月后,男性的能量消耗和两性长期的代谢率都增加了.
长期治疗增加了对PVH的OREXIGENIC/ANOREXIGENIC预测,特别是在女性中.
脑下垂体RNA-seq揭示了胰岛素信号传递,糖原溶解,神经信号传递和线粒体功能通路的性别特异上调,男性显示出更明显的效应.

结论:

卡纳在衰老期间对下丘脑代谢控制产生性别特异性影响.
该药物以性别依赖的方式影响神经保护和代谢途径.
这些发现突出了Cana in aging对下丘脑神经保护的潜在性别特异性目标.

关键词:

脑子脑子脑子脑子在Canagliflozin中使用.下丘脑的下丘脑是什么意思长寿长寿是一个问题.代谢过程中的代谢.

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