Within the spinal cord injured (SCI) population, metabolic dysfunction may be exacerbated. Models of cord injury coupled with metabolic stressors have translational relevance to understand disease progression in this population. In the present study, we used a rat model of thoracic SCI at level T10 (tSCI) and administered diets comprised of either 9% or 40% butterfat to create a unique model system to understand the physiology of weight regulation following cord injury. SCI rats that recovered on chow for 28 days had reduced body mass, lean mass, and reduced fat mass but no differences in percentage of lean or fat mass composition. Following 12 weeks on either low‐fat diet (LFD) or high‐fat diet (HFD), SCI rats maintained on LFD did not gain weight at the same rate as SCI animals maintained on HFD. LFD‐SCI had reduced feed conversion efficiency in comparison to Sham‐LFD whereas tSCI‐HFD were equivalent to Sham‐HFD rats. Although SCI rats still maintained lower lean body mass, by the end of the study HFD‐fed rats had higher body fat percentage than LFD‐fed rats. Macronutrient selection testing demonstrated SCI rats had a significant preference for protein over Sham rats. Analysis of metabolic cage activity showed tSCI rats had elevated energy expenditure, despite reduced locomotor activity. Muscle triglycerides and cholesterol were reduced only in LFD‐tSCI rats. These data suggest that consumption of HFD by tSCI rats alters the trajectory of metabolic dysfunction in the context of spinal cord disease progression.

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The lifetime risk for Type-2 diabetes mellitus remains higher in people with spinal cord injuries than in the able-bodied population. However, the mechanisms driving this disparity remain poorly understood. The goal of the current study was to evaluate the impact of a palatable high-fat diet (HFD) on glycemic regulation using a rodent model of moderate thoracic contusion. Animals were placed on either Chow or HFD and tolerance to glucose, insulin, and ENSURE mixed meal were investigated. Important targets in the gut-brain axis were investigated. HFD consumption equally induced weight gain in SCI and naïve rats over CH rats. Elevated blood glucose was observed during intraperitoneal GTT in HFD-fed rats over CH-fed rats. ITT was unremarkable amongst the three groups. Gavage of ENSURE resulted in high GLP-1 release from SCI rats over naïve controls. An elevation in terminal total GLP-1 was measured, with a marked reduction in circulating dipeptidyl peptidase 4 (DPP4), the GLP-1 cleaving enzyme, in SCI rats, compared to naïve. Increased glucagon mRNA in the pancreas and reduced immunoreactive glucagon-positive staining in the pancreas in SCI rats compared to controls suggested increased glucagon turnover. Finally, GLP-1 receptor gene expression in the ileum, the primary source of GLP-1 production and release, in SCI rats suggests the responsivity of the gut to altered circulating GLP-1 in the body. In conclusion, the actions of GLP-1 and its preprohormone, glucagon, are markedly uncoupled from their actions on glucose control in the SCI rat. More work is required to understand GLP-1 in the human.

Study Design: Basic science animal research study. Objectives: Using T10 spinal contused rats, we sought to identify molecular and circulating, metabolic and immune biomarkers during the subchronic and chronic recovery periods that may inform us concerning neurorehabilitation. Methods: Gene expression of the cord and ELISA were performed in 28 and 100 days in T10 injured rats and compared to sham-injured rats. Hundred-day injured rats were placed on either a low-fat or high-fat diet following the recovery phase. Linear regression analysis was performed between markers and locomotor score, body weight, body composition, and blood cholesterol and triglycerides. Results: Gene expression in the thoracic cord for complement marker, C1QC, dendritic cell marker, ITGAX, and cholesterol biosynthesis genes, FDFT1, HMCGR, LDLR, and SREBP1, were significantly associated with BBB score, body weight, composition, and other metabolic parameters. Circulating levels of these proteins, however, did not vary by injury or predict the level of locomotor recovery. Conclusions: Identification of reliable circulating biomarkers that are durable and based on level of spinal injury are complicated by immune and metabolic comorbidities. Continued work is necessary to identify stable markers of disease progression.