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A High-fat Diet Induces a Loss of Midbrain Dopaminergic Neuronal Function That Underlies Motor Abnormalities.
Experimental Neurobiology ( IF 2.4 ) Pub Date : 2017-04-21 , DOI: 10.5607/en.2017.26.2.104
Yunseon Jang 1, 2 , Min Joung Lee 1, 2 , Jeongsu Han 1, 2 , Soo Jeong Kim 1, 2 , Ilhwan Ryu 1, 2 , Xianshu Ju 1, 2 , Min Jeong Ryu 1, 2, 3 , Woosuk Chung 4 , Eungseok Oh 5 , Gi Ryang Kweon 1, 2, 3 , Jun Young Heo 1, 2, 6
Affiliation  

Movement defects in obesity are associated with peripheral muscle defects, arthritis, and dysfunction of motor control by the brain. Although movement functionality is negatively correlated with obesity, the brain regions and downstream signaling pathways associated with movement defects in obesity are unclear. A dopaminergic neuronal pathway from the substantia nigra (SN) to the striatum is responsible for regulating grip strength and motor initiation through tyrosine hydroxylase (TH) activity-dependent dopamine release. We found that mice fed a high-fat diet exhibited decreased movement in open-field tests and an increase in missteps in a vertical grid test compared with normally fed mice. This motor abnormality was associated with a significant reduction of TH in the SN and striatum. We further found that phosphorylation of c-Jun N-terminal kinase (JNK), which modulates TH expression in the SN and striatum, was decreased under excess-energy conditions. Our findings suggest that high calorie intake impairs motor function through JNK-dependent dysregulation of TH in the SN and striatum.

中文翻译:

高脂饮食会导致运动异常的中脑多巴胺能神经元功能丧失。

肥胖症中的运动缺陷与周围肌肉缺陷,关节炎和大脑运动控制功能障碍有关。尽管运动功能与肥胖呈负相关,但与肥胖运动缺陷相关的大脑区域和下游信号通路尚不清楚。从黑质(SN)到纹状体的多巴胺能神经元通路负责通过酪氨酸羟化酶(TH)活性依赖性多巴胺释放来调节抓地力和运动启动。我们发现,饲喂高脂饮食的小鼠与正常喂养的小鼠相比,在野外试验中表现出运动减少,而在垂直网格试验中失步增加。这种运动异常与SN和纹状体中TH的显着降低有关。我们进一步发现,c-Jun N末端激酶(JNK)的磷酸化,调节过剩的能量条件下减少SN和纹状体中的TH表达。我们的发现表明,高热量摄入会通过SN和纹状体中JNK依赖的TH失调来损害运动功能。
更新日期:2020-08-21
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