Journal
JOURNAL OF LIPID RESEARCH
Volume 60, Issue 1, Pages 58-70Publisher
ELSEVIER
DOI: 10.1194/jlr.M086843
Keywords
diabetes; dyslipidemias; apoptosis; palmitate; stearate; laurate; myristate; mitochondrial depolarization
Categories
Funding
- National Institutes of Health [R24 DK082841, R01 DK107956, F32 1F32DK112642, T32 1T32DK101357]
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [DK076169]
- Novo Nordisk [NNF14OC0011633]
- American Diabetes Association
- Program for Neurology Research and Discovery
- A. Alfred Taubman Medical Research Institute
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Dyslipidemia associated with T2D leads to diabetic neuropathy, a complication characterized by sensory neuronal dysfunction and peripheral nerve damage. Sensory dorsal root ganglion (DRG) neurons are dependent on axonal mitochondrial energy production facilitated by mitochondrial transport mechanisms that distribute mitochondria throughout the axon. Because long-chain saturated FAs (SFAs) damage DRG neurons and medium-chain SFAs are reported to improve neuronal function, we evaluated the impact of SFA chain length on mitochondrial trafficking, mitochondrial function, and apoptosis. DRG neurons were exposed to SFAs with C12:0-C18:0 chain lengths and evaluated for changes in mitochondrial trafficking, mitochondrial polarization, and apoptosis. DRG neurons treated with C16:0 and C18:0 SFAs showed a significant decrease in the percentage of motile mitochondria and velocity of mitochondrial trafficking, whereas C12:0 and C14:0 SFAs had no impact on motility. Treatment with C16:0 and C18:0 SFAs exhibited mitochondrial depolarization correlating with impaired mitochondrial motility; the C12:0- and C14:0-treated neurons retained mitochondrial polarization. The reduction in mitochondrial trafficking and function in C16:0- and C18:0-treated DRG neurons correlated with apoptosis that was blocked in C12:0 and C14:0 SFA treatments. These results suggest that SFA chain length plays an important role in regulating axonal mitochondrial trafficking and function in DRG neurons.
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