Clapping jumping jacks to improve endothelial function in obese adults: if you're happy and you NO it, clap your hands

Physical inactivity and sedentary lifestyle are risk factors for obesity which may lower quality of life and increase risk for cardiovascular disease (CVD) morbidity and mortality. Obesity detrimentally alters vascular structure and function. Individuals who are obese and sedentary tend to exhibit lower capillary density. This is important because after ingesting food or exercising, obese individuals may show altered rates of skeletal muscle vasodilatation. Thus, vascular dysfunction inhibits the ability of skeletal muscles to meet metabolic demands. Metabolic supply-demand imbalances can lead to microvascular abnormalities and insulin resistance. An impaired vasodilatory response is reported in obesity and is marked by decreased nitric oxide (NO) bioavailability; there is an altered balance between NO producing enzymes (eNOS) and NO quenching enzymes ((NAD(P)Hoxidase). Imbalance between NO formation and NO quenching leads to the increase of superoxide anions that act as free radicals in the body to induce oxidative stress. Oxidative stress propagates further reduction in NO availability. While exercise has many health benefits such as improving cardiorespiratory fitness (CRF) and reducing metabolic risk factors, many individuals do not engage in a regular exercise regimen, citing ‘lack of time’ as the underlying culprit. High intensity training (HIT) is a time-effective and aerobically beneficial mode of exercise, alternative to moderate-intensity continuous training (MICT), for cardiometabolic disease risk management. However, low-volume protocols at a high-intensity have been reported as strenuous, presenting complex barriers to obese individuals. Without supervision, adherence can be low. Laboratory-based HIT protocols may not accurately mimic the applicability and feasibility of home-based HIT protocols. In an article recently published in The Journal of Physiology, Scott and colleagues evaluated the effect of a virtually supervised at-home HIT programme on muscle capillarization and muscle microvascular eNOS/NAD(P)Hoxidase ratio in obese individuals with elevated CVD risk (Scott et al. 2019). Flow-mediated dilatation (FMD) was used to assess brachial artery NO-mediated endothelial function. FMD significantly increased after HIT training, with no difference between HIT groups. Pulse wave velocity (PWV) significantly decreased after the 12-week mark in all three HIT groups, suggesting a reduction in aortic stiffness. Blood pressure (BP) remained unchanged. These data suggest that HIT training may enhance endothelial function and reduce aortic stiffness in obese adults. Obesity and lack of physical activity affect the balance between eNOS and eNOS serine1177. Immunofluorescence microscopy using cryosectioned muscle biopsy samples was used to analyse NO-producing enzymes (eNOS content and ser1177 phosphorylation) and NO quenching enzymes (NOX2 and p47phox) that critically suppresses the effect of NO. When normalized to eNOS content (eNOS ser1177/eNOs ratio), Ser1177 content levels decreased in the arterioles and capillaries with training. Terminal arteriole NOX2 content and skeletal capillary NOX2 content was significantly lower in all groups following HIT training. Increased eNOS content and reduced NOX2 content suggest an improved balance between NO synthesis and NO quenching by superoxide anion, resulting in enhanced microvascular NO bioavailability. From the image analysis using immunofluorescence microscopy, capillarization measures were quantified specific to fibres, containing at least 50 completed fibres per assessment. Capillary-to-fibre ratio, capillary-fibre perimeter exchange index and capillary contacts (number of capillaries around a fibre) were all increased by training and were all higher in type I fibres than type II fibres, with no group differences. Augmented capillarization measures may allow for an increased O2 delivery and extraction, probably contributing to the higher seen with HIT training reported by Scott et al. (2019) and throughout the literature in obese adults. GLUT4 and intramuscular triglyceride content (IMTG) were chosen as classical markers for myocyte adaptations to training. Total muscle fibre GLUT4 content was augmented following training, with a similar increase in GLUT4 content in type II fibres across the HIT groups. HIT training increased total IMGT content in all three groups, governed by an increase in lipid droplet density. Although insulin resistance is coupled with high IMGT, these results suggest that there is a greater capacity to oxidize IMGT. There is a greater efficiency of the muscle to consume fatty acids from the IMGT pool for oxidation. Increased GLUT4 coupled with increased IMGT oxidation may lead to an overall improvement in insulin sensitivity. Scott et al. (2019) eloquently demonstrated that a home-based HIT programme can effectively improve vascular function, endothelial eNOS regulation, capillarization and myocyte adaptations in obese individuals. Another noteworthy finding, less touched on by the authors, is the improvement of cardiovascular risk markers after home-based HIT intervention. Elevated BMI is associated with increased aortic stiffness (Croymans et al. 2014), a strong predictor of heart failure, kidney disease, stroke, myocardial infarction and cognitive decline; all important co-morbidities of obesity. Scott & colleagues (2019) determined that PWV was reduced after 12 weeks of HIT in obese individuals. Central aortic stiffness is mediated by many factors including arterial wall distending pressure and smooth muscle tone. Thus, reductions in aortic stiffness with exercise training may be related to improvements in endothelial function, as NO contributes to arterial compliance (Sugawara et al. 2009). Improvements in PWV may also be related to reductions in sympathetic nervous system (SNS) activity, a mechanism not explored by Scott et al. SNS activity is an important regulator of smooth muscle tone and has been shown to be elevated in the obese population (Figueroa et al. 2012). An increase in SNS activity results in vasoconstriction and increased vascular resistance, which can lead to increased aortic stiffness. Therefore, it is plausible to conclude that 12 weeks of progressive HIT training may effectively reduce SNS activity and relax smooth muscle tone, resulting in reduced PWV in obese individuals (Sugawara et al. 2009). Understanding potential mechanisms of improved vascular function with exercise is important for designing targeted interventions to improve cardiometabolic health in obesity. Scott et al. (2019) demonstrated that adherence to an at-home HIT exercise programme is achievable for obese adults. This is noteworthy, as many may think that the difficulty of exercises used in a home HIT programme such as that described by Scott et al. (2019) may deter participation. Indeed, excess body fat may limit range of motion and prevent participants from performing exercises appropriately. Moreover, jumping tasks and high impact plyometric-type movements are often thought to increase stress on joints, which could lead to orthopedic complications and musculoskeletal injury in overweight and obese adults. However, this was not case. HIT training was demonstrated to be a safe and effective exercise modality for obese adults. In summary, Scott et al. (2019) demonstrated that a home-based HIT programme aids in removing barriers to exercise and improved cardiovascular health markers in obese adults. Obese individuals can take comfort in ‘NO-ing’ that improved metabolic and vascular health is only a few weeks of clapping jumping jacks away! None declared. All authors have approved the final version of the manuscript and agree to be accountable for all aspects of the work. All persons designated as authors qualify for authorship, and all those who qualify for authorship are listed. None declared. We'd like to acknowledge Dr Kevin Heffernan for his helpful review of this manuscript.