The Effects of Obesity on the Inflammatory, Cardiovascular, and Neurobiological Responses to Exercise in Older Adults.

Obesity with advancing age leads to increased health complications that are involved in various complex physiological processes. For example, inflammation is a critical cardiovascular disease risk factor that plays a role in the stages of atherosclerosis in both aging and obesity. Obesity can also induce profound changes to the neural circuitry that regulates food intake and energy homeostasis with advancing age. Here we discuss how obesity in older adults impacts inflammatory, cardiovascular, and neurobiological functions with an emphasis on how exercise mediates each topic. Although obesity is a reversible disorder through lifestyle changes, it is important to note that early interventions are crucial to prevent pathological changes seen in the aging obese population. Lifestyle modifications such as physical activity (including aerobic and resistance training) should be considered as a main intervention to minimize the synergistic effect of obesity on age-related conditions, such as cerebrovascular disease.

Cerebral hemodynamics comparison using transcranial doppler ultrasound and 4D flow MRI.

Introduction: Age-related changes in cerebral hemodynamics are controversial and discrepancies may be due to experimental techniques. As such, the purpose of this study was to compare cerebral hemodynamics measurements of the middle cerebral artery (MCA) between transcranial Doppler ultrasound (TCD) and four-dimensional flow MRI (4D flow MRI). Methods: Twenty young (25 ± 3 years) and 19 older (62 ± 6 years) participants underwent two randomized study visits to evaluate hemodynamics at baseline (normocapnia) and in response to stepped hypercapnia (4% CO2, and 6% CO2) using TCD and 4D flow MRI. Cerebral hemodynamic measures included MCA velocity, MCA flow, cerebral pulsatility index (PI) and cerebrovascular reactivity to hypercapnia. MCA flow was only assessed using 4D flow MRI. Results: MCA velocity between the TCD and 4D flow MRI methods was positively correlated across the normocapnia and hypercapnia conditions (r = 0.262; p = 0.004). Additionally, cerebral PI was significantly correlated between TCD and 4D flow MRI across the conditions (r = 0.236; p = 0.010). However, there was no significant association between MCA velocity using TCD and MCA flow using 4D flow MRI across the conditions (r = 0.079; p = 0.397). When age-associated differences in cerebrovascular reactivity using conductance were compared using both methodologies, cerebrovascular reactivity was greater in young adults compared to older adults when using 4D flow MRI (2.11 ± 1.68 mL/min/mmHg/mmHg vs. 0.78 ± 1.68 mL/min/mmHg/mmHg; p = 0.019), but not with TCD (0.88 ± 1.01 cm/s/mmHg/mmHg vs. 0.68 ± 0.94 cm/s/mmHg/mmHg; p = 0.513). Conclusion: Our results demonstrated good agreement between the methods at measuring MCA velocity during normocapnia and in response to hypercapnia, but MCA velocity and MCA flow were not related. In addition, measurements using 4D flow MRI revealed effects of aging on cerebral hemodynamics that were not apparent using TCD.

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.

The Impact of Aging on the Association Between Aortic Stiffness and Cerebral Pulsatility Index.

The central arteries dampen the pulsatile forces from myocardial contraction, limiting the pulsatility that reaches the cerebral vasculature, although there are limited data on this relationship with aging in humans. The purpose of this study was to determine the association between aortic stiffness and cerebral artery pulsatility index in young and older adults. We hypothesized that cerebral pulsatility index would be associated with aortic stiffness in older adults, but not in young adults. We also hypothesized that both age and aortic stiffness would be significant predictors for cerebral pulsatility index. This study included 23 healthy older adults (aged 62 ± 6 years) and 33 healthy young adults (aged 25 ± 4 years). Aortic stiffness was measured using carotid-femoral pulse wave velocity (cfPWV), while cerebral artery pulsatility index in the internal carotid arteries (ICAs), middle cerebral arteries (MCAs), and basilar artery were assessed using 4D Flow MRI. Cerebral pulsatility index was calculated as (maximum flow - minimum flow) / mean flow. In the combined age group, there was a positive association between cfPWV and cerebral pulsatility index in the ICAs (r = 0.487; p < 0.001), MCAs (r = 0.393; p = 0.003), and basilar artery (r = 0.576; p < 0.001). In young adults, there were no associations between cfPWV and cerebral pulsatility index in any of the arteries of interest (ICAs: r = 0.253; p = 0.156, MCAs: r = -0.059; p = 0.743, basilar artery r = 0.171; p = 0.344). In contrast, in older adults there was a positive association between cfPWV and cerebral pulsatility index in the MCAs (r = 0.437; p = 0.037) and basilar artery (r = 0.500; p = 0.015). However, the relationship between cfPWV and cerebral pulsatility index in the ICAs of the older adults did not reach the threshold for significance (r = 0.375; p = 0.078). In conclusion, age and aortic stiffness are significant predictors of cerebral artery pulsatility index in healthy adults. This study highlights the importance of targeting aortic stiffness in our increasingly aging population to reduce the burden of age-related changes in cerebral hemodynamics.

Vascular responses to simulated breath-hold diving involving multiple reflexes.

Breath-hold diving evokes a complex cardiovascular response. The degrees of hypertension induced by the diving reflex are substantial and accentuated by the underwater swimming. This condition provides a circulatory challenge to properly buffer and cushion cardiac pulsations. We determined hemodynamic changes during the diving maneuver and hypothesized that central artery compliance would be augmented during simulated breath-hold diving. A total of 20 healthy young adults were studied. Hemodynamics were measured during exercise on a cycle ergometer, apnea, face immersion in cold water (trigeminal stimulation), and simulated breath-hold diving. Arterial compliance was measured by recording the carotid artery diameter from images derived from an ultrasound machine at the cephalic portion of the common carotid artery 1-2 cm proximal to the carotid bulb, whereas arterial pressure waveforms were obtained using an arterial tonometry placed on the contralateral carotid artery and recorded on a data acquisition software. The change in diameter was divided by the change in blood pressure to calculate arterial compliance. Arterial compliance increased with simulated diving compared with rest (P = 0.007) and was elevated compared with exercise and apnea alone (P < 0.01). A significant increase in heart rate was observed with exercise, apnea, and facial immersion when compared with rest (P < 0.001). However, simulated diving brought the heart rate down to resting levels. Cardiac output increased with all conditions (P < 0.001), with an attenuated response during simulated diving compared with exercise and facial immersion (P < 0.05). Mean blood pressure was elevated during all conditions (P < 0.001), with a further elevation observed during simulated diving compared with exercise (P < 0.001), apnea (P = 0.016), and facial immersion (P < 0.001). Total peripheral resistance was decreased during exercise and facial immersion compared with rest (P < 0.001) but was increased during simulated diving compared with exercise (P < 0.001), apnea (P = 0.008), and facial immersion (P = 0.003). We concluded that central artery compliance is augmented during simulated breath-hold diving to help buffer cardiac pulsations.

An exploratory investigation of apoptotic and autophagic responses in peripheral blood mononuclear cells following maximal aerobic exercise in obese individuals.

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.

Effects of meditation compared to music listening on biomarkers in breast cancer survivors with cognitive complaints: secondary outcomes of a pilot randomized control trial.

CONTEXT: We previously reported positive behavioral effects of both daily mantra meditation and classical music listening interventions in breast cancer survivors with cancer related cognitive complaints. OBJECTIVE: The objective of this pilot study was to compare the effects of the meditation intervention to a music listening intervention on biomarkers of inflammation and cellular aging (secondary outcomes) in breast cancer survivors. DESIGN: Randomized control trial, baseline data collection (time 1), post intervention data collection (time 2) SETTING: Community-based, Central Texas PARTICIPANTS: 25 breast cancer survivors (BCS) who were 3 months to 6 years post chemotherapy completion and reported cognitive changes. INTERVENTION(S): Kirtan Kriya meditation (KK) or classical music listening (ML), 8 weeks, 12 min a day MAIN OUTCOME: Telomerase activity [TA], c-reactive protein [CRP], soluble IL-2 receptor alpha [sIL-2Rα], soluble IL-4 receptor [sIL-4R], soluble IL-6 receptor [sIL-6R], soluble tumor necrosis factor receptor II [sTNF-RII], VEGF receptor 2 [sVEGF-R2], and VEGF receptor 3 [sVEGF-R3] RESULTS: Repeated measures analysis of variance models were analyzed from time 1 to time 2 by group for each biomarker. A pattern of greater telomerase activity across time in both groups (F (1,15) = 3.98, p = .06, ω2 = 0.04); significant decreases in sIL-4R across time for both groups (F (1,22) = 6.28, p = .02, ω2 = .003); group*time effect was nominally different but not statistically different for sIL-4R (F(1,22) = 3.82, p = .06, ω2 = .001); and a pattern for a group*time effect with ML group showing higher levels of sVEGF-R3 at time 2 (F (1,20) = 2.59, p = .12, ω2 = .009). No significant effects were found for CRP, sIL-2Rα, sIL-6R, sTNF-RII, or sVEGF-R2.

Impact of acute high-intensity interval exercise on plasma pentraxin 3 and endothelial function in obese individuals-a pilot study.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

No Changes in Appetite-Related Hormones Following Swimming and Cycling Exercise Interventions in Adults with Obesity.

Swimming is a favorable and ideal modality of exercise for individuals with obesity and arthritis as it encompasses a minimal weight-bearing stress and a reduced heat load. However, the available evidence indicates that regular swimming may not be effective in reducing body weight and body fatness. A current hypothesis is that exercise in cold water stimulates appetite. We determined the effect of swimming training on appetite-related hormones. Thirty-nine adults with obesity and osteoarthritis were randomly assigned to 12 weeks of supervised swimming or cycling training. In the initial few weeks, participants exercised for 20-30 minutes/day, 3 days/week, at an exercise intensity of 40-50% of heart rate reserve (HRR). Subsequently, the intensity and duration of exercise were progressively increased to 40-45 minutes/day, 3 days/week, at an intensity of 60-70% of HRR. Fasting plasma concentrations of ghrelin, insulin, leptin, and peptide YY did not change with the swimming or cycling exercise training (p>0.05). Swimming exercise did not negatively influence appetite-related hormones in adults with obesity and osteoarthritis to impair weight loss.

Effects of full-fat dairy products on subclinical vascular function in adults with elevated blood pressure: a randomized clinical trial.

BACKGROUND: High consumption of low- and non-fat dairy products improves vascular dysfunction associated with elevated arterial blood pressure (BP). Currently, it is unknown if conventional full-fat dairy products improve vascular functions. OBJECTIVES: To determine if adding whole milk and full-fat dairy products to the normal routine diet improves vascular function in adults with elevated BP. DESIGN: Sixty adults (age ± SEM; 58 ± 2 years) with elevated BP (systolic/diastolic; 120-159/ < 99 mmHg) were randomized into a controlled crossover intervention trial consisting of two 4-week dietary periods. The high dairy condition consisted of adding four daily servings of whole milk or full-fat dairy products to the normal diet and eliminated all dairy intake during the control (no dairy) condition. A 2-week washout period separated the dietary conditions. RESULTS: Carotid-femoral pulse wave velocity (cfPWV) did not differ significantly between high dairy (11.3 ± 0.3 versus 10.9 ± 0.3 m/sec) and no dairy conditions (11.2 ± 0.3 versus 11.0 ± 0.3 m/sec). The results were consistent when ultrasound-derived vascular distension measures (arterial compliance, beta-stiffness index, and elastic modulus) were evaluated. Cardiovagal baroreceptor sensitivity (via Valsalva maneuver) demonstrated no significant difference for either dietary condition. Brachial arterial flow-mediated dilation (FMD) did not differ significantly during the high dairy (5.7 ± 0.5 versus 5.4 ± 0.6%) and no dairy conditions (6.5 ± 0.5 versus 5.6 ± 0.6%). CONCLUSIONS: The solitary addition of whole milk and full-fat dairy products has no effect on subclinical vascular function in adults with elevated BP.

Heart-Thigh Cuff Pulse Wave Velocity: A Novel Nontechnical Measure of Arterial Stiffness.

BACKGROUND: Recently, a novel index of arterial stiffness was developed to eliminate the placements of transducers on the carotid and femoral arteries and to make the measurement substantially easier. We evaluated the agreement of this new methodology with the well-established carotid-femoral pulse wave velocity (cfPWV). METHODS: A total of 50 adults (28 men and 22 women) varying widely in age and blood pressure were studied. Heart-thigh pulse wave velocity (htPWV) and cfPWV were measured and compared. RESULTS: Mean values of cfPWV and htPWV were 713 ± 145 and 699 ± 150 cm/s and were not significantly different (P = 0.43). Both cfPWV and htPWV were significantly associated with age (r = 0.80 and 0.58), body mass index (r = 0.44 and 0.31), and systolic blood pressure (r = 0.42 and 0.41). The 2 pulse wave velocity measures demonstrated a strong linear association with a Pearson correlation coefficient of 0.64 (P < 0.001). This agreement was consistent with the results of the Bland-Altman plot. CONCLUSION: The automatic htPWV method, which permits the data acquisition with minimum technical skill, time, and intrusion in an operator-independent fashion, has good potential as a screening device for assessing arterial stiffness in a clinical setting.

Does 24-h ambulatory blood pressure monitoring act as ischemic preconditioning and influence endothelial function?

Ischemic preconditioning can exert a powerful protection against a subsequent period of ischemia, via repeated inflation and deflation of a blood pressure cuff. Most often, damages of ischemia-reperfusion injury and benefits of preconditioning are evaluated via endothelial function. The ambulatory blood pressure monitoring constitutes repeated bouts of ischemia for 24 h. We examined whether repeated bouts of ischemia accumulated over 24 h influenced endothelial function. Twenty-two apparently healthy non-medicated middle-aged subjects 41 (8) years participated in the study. This study was registered with ClinicalTrials.gov (NCT03303404). Flow-mediated dilation (FMD) was measured as an index of endothelium-dependent vasodilation. The ambulatory blood pressure monitoring device went through an average of 110 (13) inflation/deflation cycles, which resulted in 46 (6) min of cumulative ischemic stimuli. Following 24-h of ambulatory blood pressure monitoring, FMD did not change significantly 6.6 (2.0) vs. 6.8 (2.7)%. Similarly, shear rate and reactive hyperemia were unchanged. We concluded that ambulatory blood pressure monitoring did not influence endothelium-dependent vasodilation acting via ischemic preconditioning.

Plasma pentraxin 3 and glucose kinetics following acute high-intensity interval exercise versus continuous moderate-intensity exercise in healthy men.

Pentraxin 3 (PTX3) is mainly synthesized and released by neutrophils to help regulate innate immunity. While plasma PTX3 concentrations are associated with improved glucose metabolism and overall metabolic health, there is evidence that significant elevations in plasma glucose downregulate circulating levels of PTX3. To examine whether this relationship would be altered in response to exercise, this study investigated the kinetics of the plasma glucose and PTX3 responses following high-intensity interval exercise (HIIE) and continuous moderate-intensity exercise (CMIE). It was hypothesized that the increased concentrations of plasma glucose following HIIE compared with CMIE would be associated with an attenuated plasma PTX3 response. Eight healthy male subjects participated in both HIIE and CMIE protocols administered as a randomized, counterbalanced design. Linear mixed models for repeated measures revealed that the overall plasma glucose response was greater following HIIE compared with CMIE (protocol × time effect: p = 0.037). Although the plasma PTX3 response was higher only at 19 min into HIIE compared with CMIE (protocol × time effect: p = 0.013), no relationships were observed between plasma glucose and PTX3 either at baseline or in response to both exercise protocols, as indicated by the area under the curve "with respect to increase" analysis. Our results indicate that exercise-mediated plasma PTX3 concentrations are independent of the plasma glucose response. In addition, the present study suggests that the neutrophil-mediated innate immune response, as indicated by plasma PTX3 response, may be activated earlier during HIIE compared with CMIE.

Acute high-intensity interval exercise induces comparable levels of circulating cell-free DNA and Interleukin-6 in obese and normal-weight 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.

The comparison of acute high-intensity interval exercise vs. continuous moderate-intensity exercise on plasma calprotectin and associated inflammatory mediators.

PURPOSE: Calprotectin promotes the release of inflammatory mediators (e.g., monocyte chemoattractant protein-1 [MCP-1] and myeloperoxidase [MPO]) during the innate immune response as a mechanism to augment leukocyte chemotaxis and phagocytosis. Although plasma calprotectin is elevated with traditional continuous moderate-intensity exercise (CME) as an indicator of the inflammatory response, high-intensity interval exercise (HIIE) has been shown to attenuate systemic inflammation while providing similar improvements in cardiovascular health. Therefore, the purpose of this study was to compare plasma levels of calprotectin, MCP-1, and MPO between acute HIIE vs. CME. METHODS: Nine healthy males (24.67±3.27yrs) were recruited to participate in HIIE and CME on a cycle ergometer. HIIE consisted of 10 repeated 60s of cycling at 90% max watts (Wmax) separated by 2min of active recovery intensity of interval exercise, whereas CME consisted of 28min of cycling at 60% Wmax. Blood samples were collected prior to, immediately post, and 30 and 60min into recovery following exercise. RESULTS: Acute HIIE elicited a lower elevation in calprotectin and MPO compared to CME. An increase in MCP-1 was observed across time in both exercise protocols. Furthermore, our analyses did not reveal any significant correlation in percent change (baseline to immediately following exercise) among calprotectin, MCP1, and MPO in neither HIIE nor CME. However, a significant positive correlation was observed in the overall release of calprotectin and MPO across all four time points in both HIIE and CME. Conclusions Our findings indicate that acute HIIE may potentially diminish the systemic release of inflammatory mediators (calprotectin and MPO) compared to CME.

Association of calprotectin with leukocyte chemotactic and inflammatory mediators following acute aerobic exercise.

The objective of this study was to examine whether acute aerobic exercise-mediated calprotectin in plasma would be associated with monocyte chemotactic protein-1 (MCP-1), myeloperoxidase (MPO), and interleukin-6 (IL-6) in healthy individuals. Eleven healthy participants, aged 18 to 30 years, were recruited to perform a 30-min bout of aerobic exercise at 75% maximal oxygen uptake. Acute aerobic exercise elicited a significant elevation across time in plasma calprotectin, MCP-1, MPO, and IL-6. Body mass index (BMI) was positively correlated with calprotectin area-under-the-curve with "respect to increase" (AUCi) and IL-6 AUCi. Furthermore, calprotectin AUCi was positively correlated with IL-6 AUCi and MPO AUCi, even after controlling for BMI. Although MPO AUCi was positively correlated with IL-6 AUCi, this relationship no longer existed after controlling for BMI. These results suggest that acute aerobic exercise could mediate innate immune response associated with calprotectin and its related leukocyte chemotactic and inflammatory mediators, especially in individuals with elevated BMI.