Adipose Tissue Differs and Correlates to Carbohydrate Metabolism and Proinflammatory Adipokines by Level of Spinal Cord Injury

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Retained differentiation capacity of human skeletal muscle satellite cells from spinal cord‐injured individuals

Despite the well‐known role of satellite cells in skeletal muscle plasticity, the effect of spinal cord injury on their function in humans remains unknown. We determined whether spinal cord injury affects the intrinsic ability of satellite cells to differentiate and produce metabolically healthy myotubes. We obtained vastus lateralis biopsies from eight spinal cord‐injured and six able‐bodied individuals. Satellite cells were isolated, grown and differentiated in vitro. Gene expression was measured by quantitative PCR. Abundance of differentiation markers and regulatory proteins was determined by Western blotting. Protein synthesis and fatty acid oxidation were measured by radioactive tracer‐based assays. Activated satellite cells (myoblasts) and differentiated myotubes derived from skeletal muscle of able‐bodied and spinal cord‐injured individuals expressed similar (P > 0.05) mRNA levels of myogenic regulatory factors. Myogenic differentiation factor 1 expression was higher in myoblasts from spinal cord‐injured individuals. Desmin and myogenin protein content was increased upon differentiation in both groups, while myotubes from spinal cord‐injured individuals contained more type I and II myosin heavy chain. Phosphorylated and total protein levels of Akt‐mechanistic target of rapamycin and forkhead box protein O signalling axes and protein synthesis rate in myotubes were similar (P > 0.05) between groups. Additionally, fatty acid oxidation of myotubes from spinal cord‐injured individuals was unchanged (P > 0.05) compared to able‐bodied controls. Our results indicate that the intrinsic differentiation capacity of satellite cells and metabolic characteristics of myotubes are preserved following spinal cord injury. This may inform potential interventions targeting satellite cell activation to alleviate skeletal muscle atrophy

Effects of two different paradigms of electrical stimulation exercise on cardio-metabolic risk factors after spinal cord injury. A randomized clinical trial

ObjectiveTo examine the combined effects of neuromuscular electrical stimulation-resistance training (NMES-RT) and functional electrical stimulation-lower extremity cycling (FES-LEC) compared to passive movement training (PMT) and FES-LEC in adults with SCI on (1) oxygen uptake (VO2), insulin sensitivity and glucose disposal in adults with SCI; (2) Metabolic and inflammatory biomarkers; (3) skeletal muscle, intramuscular fat (IMF) and visceral adipose tissue (VAT) cross-sectional areas (CSAs).Materials and methodsThirty-three participants with chronic SCI (AIS A-C) were randomized to 24 weeks of NMES-RT + FES or PMT + FES. The NMES-RT + FES group underwent 12 weeks of evoked surface NMES-RT using ankle weights followed by an additional 12 weeks of progressive FES-LEC. The control group, PMT + FES performed 12 weeks of passive leg extension movements followed by an additional 12 weeks of FES-LEC. Measurements were performed at baseline (BL; week 0), post-intervention 1 (P1; week 13) and post-intervention 2 (P2; week 25) and included FES-VO2 measurements, insulin sensitivity and glucose effectiveness using the intravenous glucose tolerance test; anthropometrics and whole and regional body composition assessment using dual energy x-ray absorptiometry (DXA) and magnetic resonance imaging to measure muscle, IMF and VAT CSAs.ResultsTwenty-seven participants completed both phases of the study. NMES-RT + FES group showed a trend of a greater VO2 peak in P1 [p = 0.08; but not in P2 (p = 0.25)] compared to PMT + FES. There was a time effect of both groups in leg VO2 peak. Neither intervention elicited significant changes in insulin, glucose, or inflammatory biomarkers. There were modest changes in leg lean mass following PMT + FES group. Robust hypertrophy of whole thigh muscle CSA, absolute thigh muscle CSA and knee extensor CSA were noted in the NMES-RT + FES group compared to PMT + FES at P1. PMT + FES resulted in muscle hypertrophy at P2. NMES-RT + FES resulted in a decrease in total VAT CSA at P1.ConclusionNMES-RT yielded a greater peak leg VO2 and decrease in total VAT compared to PMT. The addition of 12 weeks of FES-LEC in both groups modestly impacted leg VO2 peak. The addition of FES-LEC to NMES-RT did not yield additional increases in muscle CSA, suggesting a ceiling effect on signaling pathways following NMES-RT.Clinical trial registrationidentifier NCT02660073

Oral baclofen administration in persons with chronic spinal cord injury does not prevent the protective effects of spasticity on body composition and glucose homeostasis

Study design: Correlation study. Objectives: To determine the effects of oral baclofen on body composition (fat mass (FM), fat-free mass (FFM)), extra-and intracellular fluid compartments and glucose homeostasis (plasma glucose and plasma insulin concentrations) in individuals with spinal cord injury (SCI) after controlling for spasticity. Settings: Laboratory settings at the University of Michigan, MI, USA. Methods: Fifteen individuals with chronic motor complete SCI (32 +/- 8 years old, 25 +/- 5 kg/m(2), C6-T11, American Spinal Injury Association A and B) underwent multifrequency bioelectrical impedance analysis to measure body composition and body fluid compartments. Spasticity of the hip, knee and ankle flexors and extensors was measured using a modified Ashworth Scale and the dose of daily oral baclofen was recorded. After overnight fasting, plasma glucose and insulin sensitivity were measured in response to an oral glucose tolerance test. Results: Oral baclofen dose was positively related to body mass index, but not to extensor or flexor spasticity. The dose of baclofen seemed to be correlated to extensor spasticity after considering spasticity per FFM. The increased dose of oral baclofen was positively associated with increased FFM, extra-and intracellular fluid compartments and total body water, but not with FM. Oral baclofen dose was negatively associated with the homeostatic model assessment index. Conclusion: Administration of oral baclofen did not attenuate the protective effects of spasticity on body composition and metabolic profile after SCI. The possibility that oral baclofen could exert an independent protective effect needs to be further investigated. Spinal Cord (2010) 48, 160-165; doi: 10.1038/sc.2009.105; published online 18 August 200