Characterization of diabetic peripheral neuropathy in a high-fat diet mouse model

Diabetic peripheral neuropathy (DPN) is characterized by progressive and symmetrical sensory alterations and constitutes one of the earliest and main complications of diabetes. Several mouse models have been developed to mimic the pathogenesis of DPN with some discrepancies to fully recapitulate the human disease. In the present study, we aimed to characterize the onset and progression of peripheral neuropathy in mice fed with 45% kcal High Fat Diet (HFD) for 16 weeks. Our data show that mice fed with this diet developed obesity, dyslipidemia, hyperglycemia, impaired glucose tolerance and insulin resistance. Using sensory tests, we found that HFD-fed mice developed mechanical hypoalgesia and thermal hyperalgesia starting after 12 weeks of diet. Our analysis of glabrous foot skin innervation revealed a decrease in intraepidermal nerve fiber density (IENFD) associated with a significant reduction of nociceptive Schwann cells (nSCs) in neuropathic mice after 16 weeks of HFD. Overall, this study shows that mice fed with a 45% kcal HFD recapitulate the main metabolic, behavioral and anatomical changes generally observed in patients with DPN and represent a reliable model to study the pathogenesis of the disease.