ABSTRACT
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.
ABSTRACT
Bariatric surgery produces significant positive benefits to recipients such as significant body fat loss and resolution of the various obesity-related comorbidities, such as reduced reproductive function. Females of childbearing age seek bariatric surgical remedies to improve their chance of successful pregnancy; however, limited knowledge exists on the impact of surgical weight loss to subsequently born offspring. We previously reported that circulating leptin levels were reduced in pregnant females having previously received vertical sleeve gastrectomy (VSG) in comparison to control dams having received Sham surgery. Furthermore, the levels of leptin receptors in the VSG placenta were also reduced in VSG. These data suggest a significant difference in leptin signaling during pregnancy that may produce an altered developmental environment for the offspring. Here, we investigate the adult offspring of dams having received VSG or Sham-VSG prior to pregnancy. Endogenous fasting plasma leptin levels were not different between Sham and VSG offspring. Fasting leptin receptor mRNA in the medial basal hypothalamus (MBH) was elevated in VSG offspring in comparison to Sham. Intraperitoneal administration of exogenous leptin produced reductions in acute food intake in male Sham offspring, but did not reduce food intake at any time point measured in male VSG offspring. Using Western blot, we identified elevated pSTAT3 and pSTAT3/STAT3 ratios in the MBH of post-VSG offspring in comparison to controls. Using immunohistochemistry, we found an increased number of pSTAT positive cells in the arcuate nucleus in the Sham offspring in comparison to VSG. In contrast, within the paraventricular and ventromedial nuclei in the hypothalamus of the VSG offspring had elevated numbers of pSTAT-positive cells in comparison to controls. Collectively, these data support our hypothesis that leptin signaling is dysregulated in VSG offspring and may be partially responsible for the long-term impact of maternal bariatric surgery on the metabolic health of offspring.
ABSTRACT
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.
