Exp Neurobiol.  2017 Apr;26(2):104-112. 10.5607/en.2017.26.2.104.

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

• Jang Y
• Lee MJ
• Han J
• Kim SJ
• Ryu I
• Ju X
• Ryu MJ
• Chung W
• Oh E
• Kweon GR
• Heo JY

• KMID: 2376578
• DOI: http://doi.org/10.5607/en.2017.26.2.104

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.

Keyword

Dopaminergic neuron; Obesity; Motor abnormality; Tyrosine hydroxylase

MeSH Terms

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
Dopamine
JNK Mitogen-Activated Protein Kinases
Tyrosine 3-Monooxygenase