The Comparison of High-Intensity Interval Exercise vs. Continuous Moderate-Intensity Exercise on C1q/TNF-Related Protein-9 Expression and Flow-Mediated Vasodilation in Obese Individuals

PURPOSE: A recent novel adipocytokine, C1q/TNF-related protein-9 (CTRP9), has been shown to increase activation of endothelial nitric oxide synthase and reduce vasoconstrictors (e.g., endothelin-1). In addition, CTRP9 may play a compensatory role in obesity-related endothelial dysfunction. Although there is limited information regarding exercise-mediated CTRP9, high-intensity interval exercise (HIIE) has been shown to be as or more effective than continuous moderate-intensity exercise (CME) in improving indicators of endothelial function (e.g., brachial artery flow-mediated dilation [BAFMD]). Therefore, the purpose of this study was to investigate the effect of acute HIIE vs. CME on serum CTRP9 and BAFMD responses in obese individuals. METHODS: Sixteen young male subjects (9 obese and 7 normal-weight) participated in a counterbalanced and caloric equated experiment: HIIE (30 minutes, 4 intervals of 4 minutes at 80-90% of VO2max with 3 minutes rest between intervals) and CME (38 minutes at 50-60% VO2max). Serum CTRP9 and BAFMD, were measured prior to, immediately following exercise, and 1 hour and 2 hours into recovery. RESULTS: The concentration of serum CTRP9 was significantly increased immediately following acute HIIE and CME in both obese and normal-weight groups (p = 0.003). Furthermore, both significant treatment by time and group by time interactions for BAFMD were observed following both exercise protocols (p = 0.018; p = 0.009; respectively), with a greater CME-induced BAFMD response at 2 hours into recovery in obese compared to normal-weight subjects. Additionally, a positive correlation in percent change (baseline to peak value) between CTRP9 and BAFMD was found following acute CME (r = 0.589, p = 0.016). CONCLUSIONS: Acute HIIE is as effective as CME to upregulate CTRP9 expression in both obese and normal-weight individuals, although CTRP9 may potentially improve CME-mediated BAFMD. The novel results from this study provide a foundation for additional examination of the mechanisms of exercise-mediated CTRP9 on endothelial function

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons

Extracellular vesicles from obese and diabetic mouse plasma alter C2C12 myotube glucose uptake and gene expression

Abstract Recent studies have indicated a role for circulating extracellular vesicles (EVs) in the pathogenesis of multiple diseases. However, most in vitro studies have used variable and arbitrary doses of EVs rather than interpreting EVs as an existing component of standard skeletal muscle cell culture media. The current study provides an initial investigation into the effects of circulating EVs on the metabolic phenotype of C2C12 myotubes by replacing EVs from fetal bovine serum with circulating EVs from control mice or mice with obesity and type 2 diabetes (OT2D). We report that EVs associated with OT2D decrease 2‐NBDG uptake (a proxy measure of glucose uptake) in the insulin‐stimulated state compared to controls. OT2D associated EV treatment also significantly decreased myosin heavy chain type 1 (MHCI) mRNA abundance in myotubes but had no effect on mRNA expression of any other myosin heavy chain isoforms. OT2D‐associated circulating EVs also significantly increased lipid accumulation within myotubes without altering the expression of a selection of genes important for lipid entry, synthesis, or catabolism. The data indicate that, in a severely diabetic state, circulating EVs may contribute to insulin resistance and alter gene expression in myotubes in a manner consistent with the skeletal muscle phenotype observed in OT2D

The Impact of Obesity on C1q/TNF-Related Protein-9 Expression and Endothelial Function following Acute High-Intensity Interval Exercise vs. Continuous Moderate-Intensity Exercise

C1q-TNF-related protein-9 (CTRP9) increases endothelial nitric oxide synthase and reduces vasoconstrictors. There is limited information regarding exercise-mediated CTRP9 in obesity. The purpose of this study was to compare high-intensity interval exercise (HIIE) and continuous moderate-intensity exercise (CME) on the CTRP9 response and an indicator of endothelial function (FMD) in obese participants. Sixteen young male participants (9 obese and 7 normal-weight) participated in a counterbalanced and caloric equated experiment: HIIE (30 min, 4 intervals of 4 min at 80–90% of VO2 max with 3 min rest between intervals) and CME (38 min at 50–60% VO2 max). Serum CTRP9 and FMD were measured prior to, immediately following exercise, and 1 h and 2 h into recovery. CTRP9 was significantly increased immediately following acute HIIE and CME in both groups (p = 0.003). There was a greater CME-induced FMD response at 2 h into recovery in obese participants (p = 0.009). A positive correlation between CTRP9 and FMD percent change was observed in response to acute CME when combined with both obese and normal-weight participants (r = 0.589, p = 0.016). The novel results from this study provide a foundation for additional examination of the mechanisms of exercise-mediated CTRP9 on endothelial function in individuals with obesity

Left cardiac sympathetic denervation for catecholaminergic polymorphic ventricular tachycardia

Catecholaminergic polymorphic ventricular tachycardia is a potentially lethal disease characterized by adrenergically mediated ventricular arrhythmias manifested especially in children and teenagers. Beta-blockers are the cornerstone of therapy, but some patients do not have a complete response to this therapy and receive an implantable cardioverter-defibrillator (ICD). Given the nature of catecholaminergic polymorphic ventricular tachycardia, ICD shocks may trigger new arrhythmias, leading to the administration of multiple shocks. We describe the long-term efficacy of surgical left cardiac sympathetic denervation in three young adults with catecholaminergic polymorphic ventricular tachycardia, all of whom had symptoms before the procedure and were symptom-free afterwar

Catecholaminergic polymorphic ventricular tachycardia is a potentially lethal disease characterized by adrenergically mediated ventricular arrhythmias manifested especially in children and teenagers. Beta-blockers are the cornerstone of therapy, but some patients do not have a complete response to this therapy and receive an implantable cardioverter–defibrillator (ICD). Given the nature of catecholaminergic polymorphic ventricular tachycardia, ICD shocks may trigger new arrhythmias, leading to the administration of multiple shocks. We describe the long-term efficacy of surgical left cardiac sympathetic denervation in three young adults with catecholaminergic polymorphic ventricular tachycardia, all of whom had symptoms before the procedure and were symptom-free afterward.

Catecholaminergic polymorphic ventricular tachycardia is a potentially lethal disease characterized by adrenergically mediated ventricular arrhythmias manifested especially in children and teenagers. Beta-blockers are the cornerstone of therapy, but some patients do not have a complete response to this therapy and receive an implantable cardioverter–defibrillator (ICD). Given the nature of catecholaminergic polymorphic ventricular tachycardia, ICD shocks may trigger new arrhythmias, leading to the administration of multiple shocks. We describe the long-term efficacy of surgical left cardiac sympathetic denervation in three young adults with catecholaminergic polymorphic ventricular tachycardia, all of whom had symptoms before the procedure and were symptom-free afterward