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在Adcy3中的蛋白质编码突变增加了脂肪,并改变了大鼠的情感行为,取决于性别

Mackenzie K Fitzpatrick¹, Alexandria Szalanczy¹, Angela Beeson¹

¹Department of Internal Medicine, Section on Molecular Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.

Obesity (Silver Spring, Md.)

|December 5, 2024

概括

腺酸环酶3 (Adcy3) 的一个跨膜变体增加了脂肪和改变了大鼠的行为. 在Adcy3变异如何影响新陈代谢和情绪方面观察到性别差异,这表明肥胖和抑郁症之间存在联系.

科学领域:

神经科学是一个神经科学.
代谢研究研究代谢研究
遗传学是一个遗传学.

背景情况:

腺酸环酶3 (Adcy3) 与肥胖和严重抑郁症有关.
在老鼠中发现的Adcy3的跨膜 (TM) 螺旋变体反映了人类肥胖变体.

研究的目的:

研究Adcy3TM变体在脂肪和行为中的作用.
探索Adcy3 TM变体对新陈代谢和情绪类行为的性别特异性影响.

主要方法:

创建了Adcy3 TM域突变 (Adcy3^mut/mut) 和异合性淘汰 (Adcy3^+/-) 的Wistar京都大鼠.
进行高脂肪饮食12周,测量体重,脂肪量,耐葡萄糖,食物摄入量,新陈代谢和行为.

主要成果:

与野生型大鼠相比,Adcy3^+/-和Adcy3^mut/mut大鼠的体重和脂肪量都增加了.
性别差异出现:男性显示食物摄入驱动的脂肪增加,而女性显示能量消耗驱动的脂肪减少.
在Adcy3^mut/mut的男性中,被动应对能力,记忆力和下丘脑CREB/p-AMPK信号传递都发生了变化. Adcy3^mut/mut的女性表现出类似焦虑的行为增加和p-AMPK信号的减少.

结论:

Adcy3 TM 域对蛋白质功能至关重要,影响p-AMPK和CREB信号通路.
Adcy3可能会调解肥胖和严重抑郁症之间的联系.
性行为显著调节Adcy3,代谢调节和行为表型之间的相互作用.

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