• KSBNS 2024


Original Article

Exp Neurobiol 2017; 26(2): 104-112

Published online April 30, 2017

© The Korean Society for Brain and Neural Sciences

A High-fat Diet Induces a Loss of Midbrain Dopaminergic Neuronal Function That Underlies Motor Abnormalities

Yunseon Jang1,2†, Min Joung Lee1,2†, Jeongsu Han1,2, Soo Jeong Kim1,2, Ilhwan Ryu1,2,Xianshu Ju1,2, Min Jeong Ryu1,2,3, Woosuk Chung4, Eungseok Oh5, Gi Ryang Kweon1,2,3*and Jun Young Heo1,2,6*

1Department of Biochemistry, Chungnam National University School of Medicine, 2Department of Medical Science, Chungnam National University School of Medicine, 3Research Institute for Medical Science, Chungnam National University School of Medicine, 4Department of Anesthesiology and Pain Medicine, Chungnam National University Hospital, 5Department of Neurology, Chungnam National University Hospital, 6Brain Research Institute, Chungnam National University School of Medicine, Daejeon 35015, Korea

Correspondence to: *To whom correspondence should be addressed.
Jun Young Heo, TEL: 82-42-580-8226, FAX: 82-42-580-8121
Gi Ryang Kweon, TEL: 82-42-580-8351, FAX: 82-42-580-8121
These authors contributed equally to this work.

Received: March 16, 2017; Revised: April 3, 2017; Accepted: April 5, 2017


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.

Keywords: Dopaminergic neuron, Obesity, Motor abnormality, Tyrosine hydroxylase