To identify mechanisms underlying peripheral neuropathy, this study examined altered lipid classes and gene expression profiles in mouse models of prediabetes and type 2 diabetes established using a high fat diet. These profiles were also compared to those of mice that were returned to a low-fat diet that exhibited improvements in neuropathy.
This research found that triglycerides containing saturated fatty acids were elevated in mice with neuropathy, and that associated lipid pathway dysregulation was linked to increases in an enzyme required for triglyceride synthesis. Of note, elevation of the same enzyme was evident in nerves of diabetic patients with neuropathy. This work, conducted in mouse models, supports the idea that abnormal fat-nerve signaling is important in nerve dysfunction in prediabetes and type 2 diabetes, and offers insight into potential therapeutic targets.