Tilbury, K. B. | Search bioRxiv

bioRxiv2019

Visualization and Analysis of Whole Depot Adipose Tissue Innervation

Little is known about the diversity and function of adipose tissue nerves due, in part, to the inability to effectively visualize the various nerve subtypes residing within these tissues. The tools currently available for researchers to image and quantify adipose tissue innervation are limited and dependent on optical clearing techniques and light sheet microscopy. Here we present a method of tissue processing that uses mechanical force to compress tissue to decrease tissue thickness in the z-axis by expanding it in the x and y-axes whilst leaving cells intact. This has been combined with autofluorescence quenching techniques to permit intact whole tissues to be mounted on slides and imaged on any microscope, with a complementary means to perform whole tissue neurite density quantification. We have included examples of how this technique can be used to further our current knowledge of adipose-nerve communication by characterizing the nerves, nerve-subtypes, and neurovascular interactions within subcutaneous white adipose tissue in mice.

neuroscience↗

bioRxiv2018

Neuropathy and neural plasticity in the subcutaneous white adipose depot.

The difficulty in obtaining as well as maintaining weight loss, together with the loss of metabolic control in conditions like diabetes and cardiovascular disease, may represent pathological situations of inadequate neural communication between the brain and peripheral organs and tissues. Innervation of adipose tissues by peripheral nerves provides a means of communication between the master metabolic regulator in the brain (chiefly the hypothalamus), and energy-expending and energy-storing cells in the body (primarily adipocytes). Although chemical and surgical denervation studies have clearly demonstrated how crucial adipose tissue neural innervation is for maintaining proper metabolic health, we have uncovered that adipose tissue becomes neuropathic in various conditions of metabolic dysregulation. Here, utilizing both human and mouse adipose tissues, we present evidence of adipose tissue neuropathy, or loss of innervation, under pathophysiological conditions such as obesity, diabetes, and aging, all of which are concomitant with insult to the adipose organ and metabolic dysfunction. Neuropathy is indicated by loss of nerve fiber protein expression, reduction in synaptic markers, and less neurotrophic factor expression in adipose tissue. Aging-related adipose neuropathy particularly results in loss of innervation around the tissue vasculature. These findings underscore that peripheral neuropathy is not restricted to classic tissues like the skin of distal extremities, and that loss of innervation to adipose may trigger or exacerbate metabolic diseases. In addition, we have demonstrated stimulation of adipose tissue neural plasticity with exercise, cold exposure or neurotrophic factor treatment, which may ameliorate adipose neuropathy and be a potential therapeutic option to re-innervate adipose and restore metabolic health.

neuroscience↗