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Pentraxin 3 (PTX3) has been shown to be a predictor of endothelial dysfunction in patients with increased risk of cardiovascular disease (CVD) (e.g., obesity). Circulating PTX3 concentrations are dysregulated in obese individuals and are elevated following acute aerobic exercise. High-intensity interval exercise (HIIE) has been demonstrated to be as effective as continuous moderate-intensity exercise in improving endothelial function, as indicated by brachial artery flow-mediated dilation (BAFMD), in patients with CVD. Therefore, the purpose of this study was to examine the effect of acute HIIE on plasma PTX3 and BAFMD responses in obese individuals. Eight obese and six normal-weight young males participated in acute HIIE (4 intervals of 4 min at 80–90% of VO2max; 3 min of active recovery at 50–60% VO2max). Plasma PTX3 and BAFMD were measured prior to, immediately following exercise, and one and 2 hours into recovery. Plasma PTX3 concentrations significantly increased following HIIE, yet the PTX3 response to HIIE was significantly blunted in obese compared to normal-weight participants. While the kinetic responses of BAFMD were also significantly different in obese compared to normal-weight participants, similar increases above the baseline were observed 2 hours into recovery in both groups. Finally, plasma PTX3 concentrations were not associated with BAFMD at baseline or in response to HIIE. The utilization of HIIE may serve as a time-efficient exercise prescription strategy to transiently improve endothelial function, independent of elevated plasma PTX3 concentrations, in obese individuals.

The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, has made a staggering global impact and has become one of the most pressing international health and economic crises of recent years. COVID-19 primarily affects the human respiratory system, often progressing to pneumonia and potentially death in susceptible populations (10). A recent analysis of COVID-19 cases and recovery outcomes has identified several predictors of progression severity and mortality, such as age, hypertension and cardiovascular disease, diabetes, chronic kidney disease, chronic obstructive pulmonary disease, cancer, and immunodeficiency (7). SARS-CoV-2 mediates infection via interaction of its spike domain with angiotensin-converting enzyme 2 (ACE2) of host cells (8, 23). Viral transmission and symptom severity are enhanced through the elegant exploitation of host cellular proprotein convertase furin, and cell-surface proteases to facilitate S2 spike domain-mediated membrane fusion (8, 23). Both cardiac and skeletal muscle tissues exhibit robust expression of ACE2 (17, 20), suggestive of potential SARS-CoV-2 infection susceptibility in both tissue types. Notably, skeletal muscle weakness, fatigue, pain, and injury occurrence are common symptoms of COVID-19 manifestation (10, 10a, 12, 25, 29). Thus it is plausible to suggest SARS-CoV-2 may directly impact skeletal muscle (Fig. 1). Here we review the current insights into COVID-19 as it relates to potential skeletal muscle susceptibility. We then aim to describe the importance of skeletal muscle in facilitating respiration, while highlighting our unique position regarding respiratory muscle vulnerability in the context of COVID-19 disease outcomes and skeletal muscle myopathies. Open in a separate window Fig. 1. Representative diagram displays the potential spread of SARS-CoV-2 into skeletal muscle and the cause of myopathies.

Autophagy is a critical molecular process in promoting cell survival against apoptosis. This study examined whether maximal aerobic exercise-mediated apoptosis in obesity might be underlying the involvement of autophagy in the peripheral blood mononuclear cells (PBMCs). Twelve healthy male subjects (6 obese and 6 normal-weight) were recruited to participate in a maximal graded exercise test on a treadmill. Obese subjects exhibited a significantly lower Bax, but a higher Bcl-2 protein level in conjunction with a reduced Bax/Bcl-2 AUCi compared to normal-weight subjects following exercise. Furthermore, a greater LC3-II/LC3-I ratio and LC3-II/LC3-I AUCi was observed in obese subjects compared to normal-weight subjects. LC3-II/LC3-I AUCi was also positively associated with obesity-associated parameters (BMI, waist/hip circumference, and fasting insulin level), but was negatively correlated with Bax/Bcl-2 AUCi. These findings demonstrate that maximal aerobic exercise differentially mediates the intrinsic apoptotic pathway and autophagic activity in human PBMCs isolated from obese compared to normal-weight individuals.

Stroke is a leading cause of mortality and long-term disability in patients worldwide. Skeletal muscle is the primary systemic target organ of stroke that severely induces muscle wasting and weakness, which contributes more to the long-term functional disability in stroke patients than any other disease. Currently, no approved pharmacological drug is available to treat stroke-induced muscle loss. Rehabilitative therapy is the only available option to improve muscle function in stroke patients. However, higher muscle fatigability and lower muscle strength from extensive muscle wasting in post-stroke patients provide poor rehabilitative outcomes. As a result, about two-thirds of stroke survivors persist in a state of insufficient recovery and experience physical disability that drastically reduces their health and quality of life. The major challenge in the drug discovery effort for treating post-stroke muscle wasting is the lack of our understanding of the molecular and/or cellular mechanisms that underlie the muscle wasting in stroke. To understand the molecular origin of stroke-induced muscle atrophy, gene expression profiling and associated biological pathway enrichment studies were performed in a mouse model of cerebral ischemic stroke using high-throughput RNA sequencing and extensive bioinformatic analyses. RNA-seq data revealed that the elevated atrophy in skeletal muscle observed in response to stroke was primairly associated with the altered expression of genes involved in the muscle protein degradation pathway. Further analysis of RNA-seq data identified Sirtuin1 (SirT1) as a critical protein that plays a significant role in regulating post-stroke muscle mass. SirT1 gain-of-function in skeletal muscle significantly reversed stroke-induced muscle atrophy via inhibiting the activation of the ubiquitin proteasomal pathway and restoring autophagy function. Collectively, this study identified suppression of SirT1as a novel mechanism by which stroke induces muscle atrophy.

Stroke is a leading cause of mortality and long-term disability in patients worldwide. Skeletal muscle is the primary systemic target organ of stroke that induces muscle wasting and weakness, which predominantly contribute to functional disability in stroke patients. Currently, no pharmacological drug is available to treat post-stroke muscle morbidities as the mechanisms underlying post-stroke muscle wasting remain poorly understood. To understand the stroke-mediated molecular changes occurring at the transcriptional level in skeletal muscle, the gene expression profiles and enrichment pathways were explored in a mouse model of cerebral ischemic stroke via high-throughput RNA sequencing and extensive bioinformatic analyses. RNA-seq revealed that the elevated muscle atrophy observed in response to stroke was associated with the altered expression of genes involved in proteolysis, cell cycle, extracellular matrix remodeling, and the neuromuscular junction (NMJ). These data suggest that stroke primarily targets muscle protein degradation and NMJ pathway proteins to induce muscle atrophy. Collectively, we for the first time have found a novel genome-wide transcriptome signature of post-stroke skeletal muscle in mice. Our study will provide critical information to further elucidate specific gene(s) and pathway(s) that can be targeted to mitigate accountable for post-stroke muscle atrophy and related weakness.

Obesity may attenuate the expression of brain-derived neurotrophic factor (BDNF), thereby increasing the risk of cognitive dysfunction. High-intensity interval exercise (HIIE) has been shown to be as or more effective than continuous moderate-intensity exercise (CME) in promoting the expression of BDNF in normal-weight individuals. Therefore, the primary purpose of this study was to examine whether or not acute HIIE could be utilized as a practical model to explore the BDNF response in obese versus normal-weight subjects when compared to acute CME. The potential relationship of exercise-induced BDNF with blood lactate and cortisol was also examined. Twelve male subjects (six obese and six normal-weight) participated in a counterbalanced and caloric equated experiment: HIIE (30 min, 4 intervals of 4 min at 80%–90% of VO2max with 3 min of active recovery at 50–60% VO2max) and CME (38 min at 50%–60% VO2max). Blood samples were collected prior to, immediately following exercise, and 1 h into recovery for measurements of serum BDNF, blood lactate, and plasma cortisol. Our results showed that the BDNF response to acute HIIE was greater than CME in obese subjects when compared to normal-weight subjects. Similarly, although acute HIIE induced greater blood lactate and plasma cortisol levels than CME, obese subjects produced less blood lactate, but no difference in cortisol than normal-weight subjects. These findings suggest that acute HIIE may be a more effective protocol to upregulate BDNF expression in an obese population, independent of increased lactate and cortisol levels. Impact statement High-intensity interval exercise (HIIE) has been shown to be a time-efficient exercise strategy that provides similar or superior physiological benefits as traditional continuous moderate-intensity exercise (CME). Our previous study demonstrated an equivalent elevation on the BDNF response in both obese and normal-weight individuals following 30 min of acute CME. To discover a time-efficient exercise strategy to improve brain health in an obese population, the present study found that obese individuals elicit a greater level of BDNF following acute HIIE versus CME than normal-weight individuals. These findings indicate that acute HIIE may be an effective strategy to upregulate BDNF expression in obese individuals.

Aims Obesity is associated with lipid aggregation in adipocytes and macrophage infiltration, leading to increased oxidative stress and inflammation. Increased cell-free DNA (cfDNA) concentrations have been observed in clinical conditions of systemic inflammation. While the beneficial effects of regular physical activity on the release of circulating cfDNA still remain unknown, acute intense exercise has been shown to increase inflammatory cytokines and cfDNA concentrations in normal-weight individuals. Therefore, the primary purpose of this study was to examine the effect of acute high-intensity interval Exercise (HIIE) on plasma cfDNA and interleukin-6 (IL-6) responses in obese and normal-weight subjects. Main methods Fourteen male subjects (7 obese and 7 normal-weight) participated in an acute HIIE protocol (30 min, 4x4min @ 80% - 90% of VO2max) on a treadmill. Between HIIE intervals, subjects performed 3 min of active recovery at 50–60% VO2max. Blood samples were collected prior to, immediately following exercise, and one hour into recovery for measurements of plasma cfDNA and IL-6. Key findings Our results demonstrated a significant elevation in plasma cfDNA immediately following acute HIIE in both obese and normal-weight subjects. A comparable elevation in the concentration of plasma IL-6 was also found between two groups in response to acute HIIE. Furthermore, the level of plasma cfDNA was not correlated with IL-6 either at baseline or in response to acute HIIE. Significance These findings may support the utilization of HIIE as a time-efficient exercise protocol to understand the obesity-associated cfDNA and inflammatory responses.