Guilford BL, Ryals JM, E Lezi, Swerdlow RH and Wright DE
Background: Mitochondrial dysfunction is purported as a contributory mechanism underlying diabetic neuropathy, but a defined role for damaged mitochondria in diabetic nerves remains unclear, particularly in standard diabetes models. Experiments here used a high-fat diet in attempt to exacerbate the severity of diabetes and expedite the time-course in which mitochondrial dysfunction may occur. We hypothesized a high-fat diet in addition to diabetes would increase stress on sensory neurons and worsen mitochondrial dysfunction.
Methods: Oxidative phosphorylation proteins and proteins associated with mitochondrial function were quantified in lumbar dorsal root ganglia. Comparisons were made between non-diabetic and streptozotocininduced (STZ) C57Bl/6 mice fed a standard or high-fat diet for 8 weeks.
Results: Complex III subunit Core-2 and voltage dependent anion channel were increased (by 36% and 28% respectively, p<0.05) in diabetic mice compared to nondiabetic mice fed the standard diet. There were no differences among groups in UCP2, PGC-1α, PGC-1β levels or Akt, mTor, or AMPK activation. These data suggest compensatory mitochondrial biogenesis occurs to offset potential mitochondrial dysfunction after 8 weeks of STZinduced diabetes, but a high-fat diet does not alter these parameters.
Conclusion: Our results indicate mitochondrial protein changes early in STZ-induced diabetes. Interestingly, a high-fat diet does not appear to affect mitochondrial proteins in either nondiabetic or STZ- diabetic mice.