The Presence of Myelinated Nerves and Schwann Cells in White Adipose Tissue: Proximity to Synaptic Vesicle Containing Nerve Terminals and Potential Role in BTBR ob/ob Demyelinating Diabetic Neuropathy

Peripheral neuropathy is a pathophysiological state of nerve degeneration and loss of tissue innervation. The most prominent cause of small fiber neuropathy is diabetes which can be demyelinating in nature, but this has not yet been explored in adipose tissue. Both demyelinating neuropathies and axonopathies implicate Schwann cells (SCs), the peripheral glial required for nerve myelination and regeneration after injury. Here, we perform a comprehensive assessment of SCs and myelination patterns of subcutaneous white adipose tissue (scWAT) nerves, including changes that occur with obesity and other imbalanced energy states in mice and humans. We found that mouse scWAT is densely innervated by both myelinated and unmyelinated sensory and sympathetic nerves. Accordingly, scWAT is home to both myelinating and non-myelinating SCs - the greater proportion of which are myelinating. Furthermore, SCs were found closely associated with synaptic vesicle-containing nerve terminals in scWAT. Obese BTBR ob/ob mice exhibit diabetic peripheral neuropathy in scWAT, and display concordant demyelination specific to small fibers, which was also associated with a decrease in the pan-SC marker Sox10 and compensatory increase in Krox20 gene expression. Together this suggests that adipose SCs may be involved in regulating the plasticity or the neuropathy of adipose tissue nerves.