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

Abstract

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.

Prolonged high fat diet ingestion, obesity, and type 2 diabetes symptoms correlate with phenotypic plasticity in myenteric neurons and nerve damage in the mouse duodenum

“…HF diet-ingesting mice in the current study were previously shown to have high weight gain, epididymal adipose tissue mass, glucose intolerance and insulin resistance compared to mice ingesting a SC diet (Stenkamp-Strahm et al 2013a; Stenkamp-Strahm et al 2013b). Obesity and T2D characteristics were first identified in these mice after 4 weeks of HF diet ingestion, became more progressed at 8 weeks, and markedly progressed after 20 weeks.…”

“…Studies by our group have also shown a reduction in total duodenal myenteric neurons, including nNOS/VIP containing neurons, in mice fed a 72% high-fat (HF) diet for 8 weeks (Stenkamp-Strahm et al 2013a). It is well understood that the ENS undergoes a loss of cells in the duodenum and other segments during normal aging (El-Salhy et al 1999; Wade 2002; Stenkamp-Strahm et al 2013b). An analysis of ENS changes in long-standing T2D and parallel age-related changes in animals have yet to be done, however, and will be especially useful to understand GI symptoms in an aging population of human diabetics.…”

Effects of Oxaliplatin Treatment on the Enteric Glial Cells and Neurons in the Mouse Ileum

“…In vivo studies using type 1 diabetic mice have shown decreases in CNS 47 and colonic levels of GFAP. 48,49 In addition, the expression of GFAP has been reported to decrease in response to acute infection, neurodegeneration, and conditions such as Wernicke's encephalopathy, Down's syndrome, schizophrenia, bipolar disorder, and depression. 50 GFAP-null mice have delayed nerve regeneration following an injury.…”

Enteric Glial Cells: Recent Developments and Future Directions

“…12 In contrast, high-fat diet-induced obesity evoked a decline of GFAP and S100b expression in EGCs. 66 Whether these changes depend on diet composition or difference in age remains to be determined. Another disease in which changes in EGCs were recently observed is Parkinson disease.…”