Visceral Adiposity, Inflammation, and Testosterone Predict Skeletal Muscle Mitochondrial Mass and Activity in Chronic Spinal Cord Injury

Goldsmith, Jacob A.; Lai, Raymond E.; Garten, Ryan S.; Chen, Qun; Lesnefsky, Edward J.; Perera, Robert A.; Gorgey, Ashraf S.

doi:10.3389/fphys.2022.809845

Cited by 6 publications

(3 citation statements)

References 52 publications

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“…Additional benefits included decrease in VAT CSA and LDL-C profile. The association of VAT to cardio-metabolic risk factors have been well studied and this has been shown to mediated via increasing inflammatory cytokines and negatively impacting circulating testosterone and mitochondrial activity ( 48 ).…”

Section: Discussionmentioning

confidence: 99%

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

Gorgey,

Khalil,

Carter

et al. 2023

Front. Neurol.

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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.

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Section: Discussionmentioning

confidence: 99%

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

Gorgey,

Khalil,

Carter

et al. 2023

Front. Neurol.

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“… 56 In a cross-sectional study, markers of metabolic syndrome, such as increased visceral adipose tissue, elevated IL-6, and CRP, 320 and low testosterone, predicted mitochondrial dysfunction. 321 Additionally, adrenal dysfunction can increase cortisol, norepinephrine, and glucose levels, triggering mitochondrial fragmentation. 322 , 323 …”

Section: Modeling Of Sci As a Multi-system Diseasementioning

confidence: 99%

Development of a Systems Medicine Approach to Spinal Cord Injury

Guest

Kelly-Hedrick

Williamson

et al. 2023

Journal of Neurotrauma

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Traumatic spinal cord injury (SCI) causes a sudden onset multi-system disease, permanently altering homeostasis with multiple complications. Consequences include aberrant neuronal circuits, multiple organ system dysfunctions, and chronic phenotypes such as neuropathic pain and metabolic syndrome. Reductionist approaches are used to classify SCI patients based on residual neurological function. Still, recovery varies due to interacting variables, including individual biology, comorbidities, complications, therapeutic side effects, and socioeconomic influences for which data integration methods are lacking. Infections, pressure sores, and heterotopic ossification are known recovery modifiers. However, the molecular pathobiology of the disease-modifying factors altering the neurological recovery-chronic syndrome trajectory is mainly unknown, with significant data gaps between intensive early treatment and chronic phases. Changes in organ function such as gut dysbiosis, adrenal dysregulation, fatty liver, muscle loss, and autonomic dysregulation disrupt homeostasis, generating progression-driving allostatic load. Interactions between interdependent systems produce emergent effects, such as resilience, that preclude single mechanism interpretations. Due to many interacting variables in individuals, substantiating the effects of treatments to improve neurological outcomes is difficult. Acute injury outcome predictors, including blood and cerebrospinal fluid biomarkers, neuroimaging signal changes, and autonomic system abnormalities, often do not predict chronic SCI syndrome phenotypes. In systems medicine, network analysis of bioinformatics data is used to derive molecular control modules. To better understand the evolution from acute SCI to chronic SCI multi-system states, we propose a topological phenotype framework integrating bioinformatics, physiological data, and allostatic load tested against accepted established recovery metrics. This form of correlational phenotyping may reveal critical nodal points for intervention to improve recovery trajectories. This study examines the limitations of current classifications of SCI and how these can evolve through systems medicine.

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“…Persons with chronic SCI have an increased risk for obesityrelated cardiometabolic diseases, including dyslipidemia, glucose intolerance and diabetes mellitus, central obesity, systemic inflammation and mitochondrial dysfunction (13)(14)(15)(16)(17) .…”

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confidence: 99%

Trends in measuring BMR and RMR after spinal cord injury: a comprehensive review

et al. 2023

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Studying factors that contribute to our understanding of maintaining normal energy balance are of paramount significance following spinal cord injury (SCI). Accurate determination of energy needs is crucial for providing nutritional guidance and managing the increasing prevalence of malnutrition or obesity after SCI. Basal metabolic rate (BMR) represents 75-80% of the total energy expenditure in persons with SCI. Accurately measuring BMR is an important component for calculating total caloric needs in this population. Indirect calorimetry is considered the gold-standard technique for measuring BMR. However, technical challenges may limit its applications in large cohort studies and alternatively rely on prediction equations. Previous work has shown that BMR changes in response to disuse and exercise in the range of 15-120%. Factors including sex, level of injury, and type of assistive devices may influence BMR after SCI. Resting metabolic rate (RMR) is erroneously used interchangeably for BMR, which may result in overestimation of caloric intake when developing nutritional plans. To address this concern, we comprehensively reviewed studies that conducted BMR (N=15) and RMR (N=22) in persons with SCI. The results indicated that RMR is 9% greater than BMR in persons with SCI. Furthermore, the SCI-specific prediction equations that incorporated measures of fat-free mass appeared to accurately predict BMR. Overall, the current findings highlighted the significance of measuring BMR as well as encouraging the research and clinical community to effectively establish countermeasures to combat obesity after SCI.

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Visceral Adiposity, Inflammation, and Testosterone Predict Skeletal Muscle Mitochondrial Mass and Activity in Chronic Spinal Cord Injury

Cited by 6 publications

References 52 publications

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

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

Development of a Systems Medicine Approach to Spinal Cord Injury

Trends in measuring BMR and RMR after spinal cord injury: a comprehensive review

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