Chun-Jung Huang

Cardiovascular reactivity, stress, and physical activity.

Psychological stress has been proposed as a major contributor to the progression of cardiovascular disease (CVD). Acute mental stress can activate the sympathetic-adrenal-medullary (SAM) axis, eliciting the release of catecholamines (NE and EPI) resulting in the elevation of heart rate (HR) and blood pressure (BP). Combined stress (psychological and physical) can exacerbate these cardiovascular responses, which may partially contribute to the elevated risk of CVD and increased proportionate mortality risks experienced by some occupations (e.g., firefighting and law enforcement). Studies have supported the benefits of physical activity on physiological and psychological health, including the cardiovascular response to acute stress. Aerobically trained individuals exhibit lower sympathetic nervous system (e.g., HR) reactivity and enhanced cardiovascular efficiency (e.g., lower vascular reactivity and decreased recovery time) in response to physical and/or psychological stress. In addition, resistance training has been demonstrated to attenuate cardiovascular responses and improve mental health. This review will examine stress-induced cardiovascular reactivity and plausible explanations for how exercise training and physical fitness (aerobic and resistance exercise) can attenuate cardiovascular responses to stress. This enhanced functionality may facilitate a reduction in the incidence of stroke and myocardial infarction. Finally, this review will also address the interaction of obesity and physical activity on cardiovascular reactivity and CVD.

Psychological stress during exercise: immunoendocrine and oxidative responses

The purpose of this study was to examine the changes in catecholamines (epinephrine [EPI] and norepinephrine [NE]), interleukin-2 (IL-2) and a biomarker of oxidative stress (8-isoprostane) in healthy individuals who were exposed to a dual challenge (physical and psychological stress). Furthermore, this study also examined the possible relationships between catecholamines (NE and EPI) and 8-isoprostane and between IL-2 and 8-isoprostane following a combined physical and psychological challenge. Seven healthy male subjects completed two experimental conditions. The exercise-alone condition (EAC) consisted of cycling at 60% VO2max for 37 min, while the dual-stress condition (DSC) included 20 min of a mental challenge while cycling. DSC showed greater EPI and 8-isoprostane levels (significant condition by time interaction). NE and IL-2 revealed significant change across time in both conditions. In addition, following dual stress, EPI area-under-the-curve (AUC) demonstrated a positive correlation with NE AUC and IL-2 AUC. NE AUC was positively correlated with IL-2 AUC and peak 8-isoprostane, and peak IL-2 was positively correlated with peak 8-isoprostane in response to a dual stress. The potential explanation for elevated oxidative stress during dual stress may be through the effects of the release of catecholamines and IL-2. These findings may further provide the potential explanation that dual stress alters physiological homeostasis in many occupations including firefighting, military operations and law enforcement. A greater understanding of these responses to stress can assist in finding strategies (e.g. exercise training) to overcome the inherent psychobiological challenges associated with physically and mentally demanding professions.

Obesity-Related Oxidative Stress: the Impact of Physical Activity and Diet Manipulation

Obesity-related oxidative stress, the imbalance between pro-oxidants and antioxidants (e.g., nitric oxide), has been linked to metabolic and cardiovascular disease, including endothelial dysfunction and atherosclerosis. Reactive oxygen species (ROS) are essential for physiological functions including gene expression, cellular growth, infection defense, and modulating endothelial function. However, elevated ROS and/or diminished antioxidant capacity leading to oxidative stress can lead to dysfunction. Physical activity also results in an acute state of oxidative stress. However, it is likely that chronic physical activity provides a stimulus for favorable oxidative adaptations and enhanced physiological performance and physical health, although distinct responses between aerobic and anaerobic activities warrant further investigation. Studies support the benefits of dietary modification as well as exercise interventions in alleviating oxidative stress susceptibility. Since obese individuals tend to demonstrate elevated markers of oxidative stress, the implications for this population are significant. Therefore, in this review our aim is to discuss (i) the role of oxidative stress and inflammation as associated with obesity-related diseases, (ii) the potential concerns and benefits of exercise-mediated oxidative stress, and (iii) the advantageous role of dietary modification, including acute or chronic caloric restriction and vitamin D supplementation.

Stress hormones and immunological responses to a dual challenge in professional firefighters.

The purpose of this study was to examine the changes in heart rate (HR), catecholamines (norepinephrine [NE] and epinephrine [EPI]), pro-inflammatory cytokines (interleukin-2 [IL-2] and interleukin-6 [IL-6]), and lymphocytes (CD8+ and CD56+) in firefighters exposed to a decision-making challenge (firefighting strategies and tactics drill) while participating in moderate intensity exercise. Nine professional male firefighters participated in two counterbalanced exercise conditions on a cycle ergometer: (1) 37 min of cycle ergometry at 60% VO(2max) (exercise alone condition ; EAC) and (2) 37 min of cycle ergometry at 60% VO(2max) along with 20 min of a computerized firefighting strategy and tactics decision-making challenge (firefighting strategy condition; FSC). FSC elicited significantly greater HR, NE, EPI, and IL-2 when compared to EAC. These elevations may suggest that the addition of a mental challenge to physical stress can alter the hormonal and immunological responses during firefighting. In addition, this evidence provides insight into the possible mechanisms that explain the link between physical activity, psychological stress, and stress-related diseases.

Brain-derived neurotrophic factor expression ex vivo in obesity.

Obesity is associated with an increased risk in neurodegenerative diseases. To counteract the neuronal damage, the human body increases brain-derived neurotrophic factor (BDNF) expression, leading to neuronal survival and plasticity. Recently, peripheral blood mononuclear cells (PBMCs) have been found to release BDNF as a potential neuroprotective role of inflammation. Therefore, the purpose of this study was to examine whether lipopolysaccharide (LPS)-induced PBMC activation would lead to differences in BDNF and inflammatory responses between obese and non-obese subjects. Thirty-one subjects (14 obese and 17 non-obese), ages 18 to 30years, were recruited. PBMCs were cultured for 24h with 10ng/mL LPS. BDNF, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were measured in both plasma and cell culture supernatants. Our results did not illustrate any differences in plasma BDNF levels between obese and non-obese groups. However, obese subjects elicited a greater plasma IL-6 production, which was positively associated with plasma BDNF. Furthermore, LPS-induced PBMCs expressed significantly higher BDNF and IL-6 levels in obese subjects compared to the non-obese subjects. Finally, these BDNF levels were positively correlated with IL-6 response ex vivo. These findings suggest that under a high inflammatory state, PBMCs produce greater BDNF and IL-6 expression which may play a collaborative role to protect against neuronal damage associated with obesity.

Psychological stress during exercise: Lymphocyte subset redistribution in firefighters

The purpose of this study examined the changes in heart rate (HR), catecholamines (NE, EPI) and percentages of blood lymphocyte subsets (CD3+ T cells, CD3+CD4+ helper T cells, CD3+CD8+ cytotoxic T cells, CD3- CD56+ NK cells, CD4/CD8 ratio, CD19+ B cells, and total lymphocytes [NK cells+T cells+B cells]) in firefighters exposed to a computerized firefighting strategies and tactics decision-making challenge while participating in moderate intensity exercise. Furthermore, this study also examined the possible relationships between catecholamines (NE and EPI) and blood lymphocyte subsets following combined mental and physical challenge. Ten professional male firefighters participated in two counterbalanced exercise conditions on a cycle ergometer: (1) 37min of cycle ergometry at 60% VO(2max) (exercise alone condition; EAC) and (2) 37min of cycle ergometry at 60% VO(2max) along with 20min of a computerized firefighting strategies and tactics decision-making challenge (firefighting strategies condition; FSC). FSC elicited significantly greater HR, NE, and EPI when compared to EAC. Both EAC and FSC elicited increases in CD3- CD56+ NK cells. The percentages of CD3+ T cells, CD3+CD4+ helper T cells, CD4/CD8 ratio, CD19+ B cells, and total lymphocytes were lower immediately following both conditions. Following dual challenge NE AUC was negatively correlated with percentage of CD19+ B cells immediately post challenge, and HR was negatively associated with the percent change in the CD4/CD8 ratio from pre to post challenge. These elevations in NE and heart rate simultaneously in response to the dual challenge suggest greater sympathetic activation that in turn would possibly explain the alteration in the distribution of lymphocyte subsets.

A therapeutic role for vitamin D on obesity-associated inflammation and weight-loss intervention

Vitamin D plays an essential role in the regulation of skeletal metabolism as well as calcium and phosphate homeostasis, while vitamin D receptor (VDR) regulates de novo lipid synthesis, thereby contributing to the development of obesity. Furthermore, obese individuals are at a greater risk for vitamin D deficiency which may increase the potential risk for chronic inflammation, insulin resistance, and metabolic syndrome. While acute exercise enhances the activation of inflammatory signaling pathways, chronic exercise training may attenuate elevated pro-inflammatory cytokine production, resulting in the improvement of cardiovascular and metabolic health in obese individuals. Supplementation with vitamin D coupled with exercise or mild caloric restriction has been shown to improve markers of fitness and inflammation as well as cholesterol. Therefore, this review primarily addresses the impact of vitamin D deficiency in obesity-related inflammatory imbalances and how exercise and weight-loss interventions may enhance the beneficial effects on vitamin D-mediated inflammation in obesity.

LPS-stimulated tumor necrosis factor-alpha and interleukin-6 mRNA and cytokine responses following acute psychological stress

The purpose of this study was to examine the effect of acute psychological stress on LPS-stimulated TNF-α and IL-6 mRNA expression. Twenty-one healthy male subjects participated in 20 min of acute stress. Blood samples for norepinephrine and LPS-stimulated TNF-α and IL-6 cytokines and mRNA were drawn prior to, immediately after and 1-h after stress. Stress-induced increases in anxiety scores, cortisol, plasma norepinephrine, and heart rate demonstrated that the experimental protocol elicited an acute stress response. LPS-stimulated TNF-α mRNA decreased significantly immediately post-stress and partially recovered at 1h post-stress, whereas LPS-stimulated IL-6 mRNA exhibited a significant change across time, with an increase immediately after stress and a decrease 1h after stress. Trends in LPS-stimulated TNF-α and IL-6 cytokine concentrations followed the patterns of mRNA expression. A negative correlation of body mass index (BMI) and percent change of LPS-stimulated TNF-α mRNA was observed immediately post-stress, and BMI positively correlated with percent change of LPS-stimulated IL-6 cytokine levels immediately following stress. These findings demonstrated that acute psychological stress affects LPS-stimulated IL-6 and TNF-α gene expression. These results also indicate that BMI may impact the effects of psychological stress on cytokine responses to immune challenge. Further examination of the effects of stress on synthesis of other cellular cytokines and investigation of the association of BMI and stress responses will provide a more clear representation of the cytokine responses to acute psychological stress. In addition, studies examining the influence of gender on the response of immune cell subsets to acute stress and the possible mediating effect of BMI are warranted.

Cardiorespiratory fitness does not alter plasma pentraxin 3 and cortisol reactivity to acute psychological stress and exercise

Pentraxin 3 (PTX3) has been recently identified as a biomarker of vascular inflammation in predicting cardiovascular events. The purpose of this study was to examine the effect of cardiorespiratory fitness on plasma PTX3 and cortisol responses to stress, utilizing a dual-stress model. Fourteen male subjects were classified into high-fit (HF) and low-fit (LF) groups and completed 2 counterbalanced experimental conditions. The exercise-alone condition (EAC) consisted of cycling at 60% maximal oxygen uptake for 37 min, while the dual-stress condition (DSC) included 20 min of a mental stress while cycling for 37 min. Plasma PTX3 revealed significant increases over time with a significant elevation at 37 min in both HF and LF groups in response to EAC and DSC. No difference in plasma PTX3 levels was observed between EAC and DSC. In addition, plasma cortisol revealed a significant condition by time interaction with greater levels during DSC at 37 min, whereas cardiorespiratory fitness level did not reveal different plasma cortisol responses in either the EAC or DSC. Aerobic exercise induces plasma PTX3 release, while additional acute mental stress, in a dual-stress condition, does not exacerbate or further modulate the PTX3 response. Furthermore, cardiorespiratory fitness may not affect the stress reactivity of plasma PTX3 to physical and combined physical and psychological stressors. Finally, the exacerbated cortisol responses to combined stress may provide the potential link to biological pathways that explain changes in physiological homeostasis that may be associated with an increase in the risk of cardiovascular disease.

Brain‐Derived Neurotrophic Factor and Substrate Utilization Following Acute Aerobic Exercise in Obese Individuals

Brain‐derived neurotrophic factor (BDNF) serves as a vital regulator of neuronal proliferation and survival, and has been shown to regulate energy homeostasis, glucose metabolism and body weight maintenance. Elevated concentrations of plasma BDNF have been associated with obesity and type 2 diabetes mellitus. Acute aerobic exercise transiently increases circulating BDNF, potentially correcting obesity‐related metabolic impairment. The present study aimed to compare acute aerobic exercise elicited BDNF responses in obese and normal‐weight subjects. Furthermore, we aimed to investigate whether acute exercise‐induced plasma BDNF elevations would be associated with improved indices of insulin resistance, as well as substrate utilization [carbohydrate oxidation (CHOoxi) and fat oxidation (FAToxi)]. Twenty‐two healthy, untrained subjects [11 obese (four men and seven women; age = 22.91 ± 4.44 years; body mass index = 35.72 ± 4.17 kg/m2) and 11 normal‐weight (five men and six women; age = 23.27 ± 2.24 years; body mass index = 21.89 ± 1.63 kg/m2)] performed 30 min of continuous submaximal aerobic exercise at 75% maximal oxygen consumption. Our analyses showed that the BDNF response to acute aerobic exercise was similar in obese and normal‐weight subjects across time (time: P = 0.015; group: P = not significant) and was not associated with indices of IR. Although no differences in the rates of CHOoxi and FAToxi were found between both groups, total relative energy expenditure was significantly lower in obese subjects compared to normal‐weight subjects (3.53 ± 0.25 versus 5.59 ± 0.85; P < 0.001). These findings suggest that acute exercise‐elicited BDNF elevation may not be sufficient to modulate indices of IR or the utilization of either carbohydrates or fats in obese individuals.