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Characterization of Gastrointestinal Hormone Dysfunction and Metabolic Pathophysiology in Experimental Spinal Cord
Gregory E Bigford1, Angela Szeto2, Andrew J Darr3
1Department of Neurological Surgery and the Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, Florida, USA.
Insights
Spinal cord injury (SCI) disrupts gut hormones and metabolism, increasing cardiometabolic disease risk. This study reveals widespread GI effects after SCI, impacting glucose regulation and gut health.
Area of Science:
- Neuroscience
- Endocrinology
- Gastroenterology
Background:
- Cardiometabolic disease is a major complication of spinal cord injury (SCI), leading to premature death.
- The exact pathophysiology linking SCI to cardiometabolic disorders, particularly autonomic dysfunction affecting energy metabolism, remains unclear.
Purpose of the Study:
- To investigate the impact of experimental SCI on gastrointestinal (GI) peptide and hormone gene expression and physiology.
- To evaluate GI tissue changes and physiological responses to feeding and glucose/insulin challenges post-SCI.
Main Methods:
- Adult female mice underwent severe SCI (T9) or sham surgery.
- Assessed gene expression, plasma hormone levels, glucose/insulin tolerance, and GI tissue cytoarchitecture.
Main Results:
- SCI mice showed elevated fasting glucose and exaggerated glucose/insulin response.
- Significant alterations in gut hormone genes, plasma levels, feeding responses, and gut tissue damage were observed in SCI mice.
- SCI led to chronic elevation of fasting plasma glucose levels.
Conclusions:
- Experimental SCI profoundly affects the GI system, altering gut hormone regulation and contributing to cardiometabolic disease risk factors.
- These findings highlight the GI tract's role in SCI pathophysiology and suggest potential therapeutic targets for rehabilitation.
Abstract:
Cardiometabolic disease is a leading complication of spinal cord injury (SCI) that contributes to premature all-cause cardiovascular morbidity and early death. Despite widespread reports that cardioendocrine disorders are more prevalent in individuals with SCI than those without disability, a well-defined pathophysiology has not been established. Autonomic dysfunction accompanying disruption of autonomic spinal tracts may contribute to dysregulation of energy metabolism via uncoupling of integrated hunger and satiation signals. In governing human feeding behaviors, these signals are controlled by a network of enteroendocrine cells that line the gastrointestinal (GI) tract. These cells regulate GI peptide release and autonomic systems that maintain direct neuroendocrine communication between the GI tract and appetite circuitry of the hypothalamus and brainstem. Here we investigate gene-expression and physiological changes in GI peptides and hormones, as well as changes in physiological response to feeding, glucose and insulin challenge, and evaluate GI tissue cytoarchitecture after experimental SCI. Adult female mice (C57BL/6) were subjected to a severe SCI (65 kDyne) at T9, and a sham control group received laminectomy only. The SCI results in chronic elevation of fasting plasma glucose levels and an exaggerated glucose response after an oral glucose and insulin tolerance test. Mice with SCI also exhibit significant alteration in gut hormone genes, plasma levels, physiological response to prandial challenge, and cell loss and gross tissue damage in the gut. These findings demonstrate that SCI has widespread effects on the GI system contributing to component cardiometabolic disease risk factors and may inform future therapeutic and rehabilitation strategies in humans.
