High-fat diet and age-dependent effects on enteric glial cell populations of mouse small intestine.

Diabetes and obesity are increasing in prevalence at an alarming rate throughout the world. Autonomic diabetic neuropathy is evident in individuals that experience a long-standing diabetic disease state, and gastrointestinal (GI) dysmotility is thought to be the outcome of neuropathies within the enteric nervous system (ENS) of these patients. To date, an analysis of enteric glial cell population changes during diabetic symptoms has not been performed, and may bring insight into disease pathology and neuropathy, given glial cell implications in gastrointestinal and neuronal homeostasis. Diabetes and obesity were monitored in C57Bl/6J mice fed a 72% high-fat diet, and duodenal glial expression patterns were evaluated by immunohistochemistry and RT-PCR for S100β, Sox10 and GFAP proteins and transcripts, as well as transmission electron microscopy (TEM). The high-fat diet caused obesity, hyperglycemia and insulin resistance after 4 weeks. These changes were associated with a significant decline in the area density indices of mucosa-associated glial cell networks, evidenced by S100β staining at 8 and 20 weeks. All three markers and TEM showed that myenteric glial cells were unaffected by early and late disease periods. However, analysis of Sox10 transcript expression and immunoreactivity showed a diet independent, age-associated decline in glial cell populations. This is the first study showing that mucosal glia cell damage occurs during diabetic symptoms, suggesting that mucosal enteric glia injury may have a pathophysiological significance during this disease. Our results also provide support for age-associated changes in longitudinal studies of enteric glial cells.