Molecular Mechanisms of Diabetic Neuropathy

This project proposes to examine molecular mechanisms that contribute to peripheral neuropathy in diet-induced obesity. I previously showed that dietary saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs) differentially regulate nerve function in murine models of diet-induced obesity and prediabetes. Murine models fed a high-fat diet rich in SFAs develop peripheral neuropathy. Switching these mice from an SFA-rich high-fat diet to a MUFA-rich high-fat diet restores nerve function. We recently found that these changes in nerve function correlate with alterations sphingolipid levels within the sciatic nerve. Herein, we propose to evaluate the impact of SFAs and MUFAs on neuroinflammation and mitophagy in the peripheral nervous system of mice with prediabetes and neuropathy. We hypothesize that a high-fat diet rich in SFAs will induce neuroinflammation and impair mitophagy while a high-fat diet rich in MUFAs will reduce neuroinflammation, restore mitophagy, and nerve function in mice with prediabetes.