A High-fat Diet Induces a Loss of Midbrain Dopaminergic Neuronal Function That Underlies Motor Abnormalities.
- Author:
Yunseon JANG
1
;
Min Joung LEE
;
Jeongsu HAN
;
Soo Jeong KIM
;
Ilhwan RYU
;
Xianshu JU
;
Min Jeong RYU
;
Woosuk CHUNG
;
Eungseok OH
;
Gi Ryang KWEON
;
Jun Young HEO
Author Information
- Publication Type:Original Article
- Keywords: Dopaminergic neuron; Obesity; Motor abnormality; Tyrosine hydroxylase
- MeSH: Animals; Arthritis; Brain; Diet, High-Fat*; Dopamine; Dopaminergic Neurons*; Hand Strength; JNK Mitogen-Activated Protein Kinases; Mesencephalon*; Mice; Obesity; Phosphorylation; Substantia Nigra; Tyrosine 3-Monooxygenase
- From:Experimental Neurobiology 2017;26(2):104-112
- CountryRepublic of Korea
- Language:English
- Abstract: 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.
