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Obesity and diabetes often lead to peripheral neuropathy. Damage and axonal die-back of the peripheral nervous system constitutes peripheral neuropathy. By 2030, half of the US adult population is projected to be obese, and type 2 diabetes mellitus is most commonly caused by obesity. As incidences of obesity and diabetes increase, the adverse effects of neuropathy will also increase. Neuropathy, previously thought to only affect skin layers of distal extremities, has recently been discovered in subcutaneous adipose tissue depots. Obese adipose tissue is fibrotic, resulting in excess collagen deposition. Collagen organizes the peripheral nervous system, but its interaction with adipose nerves has not been thoroughly investigated. Using 2-photon microscopy combined with second harmonic generation microscopy, we examined the spatial relationship between collagen and nerve in the adipose microenvironment to gain a better understanding of neuropathy pathways and mechanisms. Pearson’s Correlation Coefficient analysis suggests that an obese diet leads to greater colocalization between nerve and collagen in adipose tissue than a lean diet. These findings motivate further investigation as the Pearson Correlation Coefficient is restrictively optimized for structures that are overlapped, whereas nerves may simply be wrapped with or tightly associated with collagen. Here we present an adaptation of the multiscale 2D Wavelet Transform Modulus Maxima method to reveal different anisotropic signatures across adiposeresiding nerve and collagen fibers in tissues from mice fed obese and lean diets, respectively. Based on these promising preliminary results, additional development of multiscale wavelet-based techniques will offer insight into neuropathy through thorough investigation of nerve and collagen spatial relationships.
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