Fabiano T. Amorim

Heat Shock Protein 72 Response to Exercise in Humans

Heat shock protein (Hsp) 72 is a unique, ubiquitous molecule. In vitro and in vivo animal models have shown that increased Hsp 72 is associated with improved cellular survivability and tolerance to stressors. The primary focus of this article is to review the Hsp 72 protein response to exercise in humans. Various mechanisms regulate post-transcriptional activity and therefore measurement of messenger RNA (mRNA) does not necessarily represent the level of functional Hsp 72. For this reason, this article incorporates only a few studies that assessed Hsp 72 mRNA response to exercise. Although this article focuses on human studies, it also includes some key animal studies to provide insight into the mechanisms of the response of Hsp 72 to stress.Intra-(IC) and extracellular (EC) Hsp 72 have different functions. IC Hsp 72 confers cellular protection from subsequent stressors, while EC Hsp 72 has a whole-body systemic role in antigen presentation and immunity. An acute exercise bout stimulates an increase in both IC and EC Hsp 72. Long-term training and improved fitness increases the rate of availability of IC Hsp 72 in response to stress. Other factors that affect Hsp 72 production include environmental factors, exercise mode, duration and intensity, age, estrogen, and anti-oxidant and glycogen availability. The functions and roles of Hsp 72 also depend on the tissue of origin. This article describes the Hsp 72 response to exercise in relation to the tissue assayed (i.e. skeletal muscle vs lymphocyte) and the origin of the sample (i.e. venous vs arterial serum). Collectively, the reviewed studies reveal exciting and novel research that encourages future investigation in this area.

Association Between Exercise-Induced Hyperthermia and Intestinal Permeability: A Systematic Review

BackgroundProlonged and strenuous physical exercise increases intestinal permeability, allowing luminal endotoxins to translocate through the intestinal barrier and reach the bloodstream. When recognized by the immune system, these endotoxins trigger a systemic inflammatory response that may affect physical performance and, in severe cases, induce heat stroke. However, it remains to be elucidated whether there is a relationship between the magnitude of exercise-induced hyperthermia and changes in intestinal permeability.ObjectiveIn this systematic review, we evaluated whether an exercise-induced increase in core body temperature (TCore) is associated with an exercise-induced increase in intestinal permeability.MethodsThe present systematic review screened the MEDLINE/PubMed and Web of Science databases in September 2016, without any date restrictions. Sixteen studies that were performed in healthy participants, presented original data, and measured both the exercise-induced changes in TCore and intestinal permeability were selected. These studies assessed intestinal permeability through the measurement of sugar levels in the urine and measurement of intestinal fatty acid binding protein or lipopolysaccharide levels in the blood.ResultsExercise increased both TCore and intestinal permeability in most of the 16 studies. In addition, a positive and strong correlation was observed between the two parameters (r = 0.793; p < 0.001), and a TCore exceeding 39 °C was always associated with augmented permeability.ConclusionThe magnitude of exercise-induced hyperthermia is directly associated with the increase in intestinal permeability.

Insights into the role of heat shock protein 72 to whole-body heat acclimation in humans

Abstract Heat acclimation results in systemic and cellular adaptions that reduce the negative effect of heat and, consequently, the risk of heat illness. Although the classical changes observed with heat acclimation lead to increased tolerance to exercise in the heat by reducing heat storage (reflected in reduced core and skin temperatures) and increasing whole-body capacity for heat dissipation (greater plasma volume, sweat output, and skin blood flow), it appears that heat acclimation also induces changes at the cellular level that might increase tolerance of the whole organism to a higher core temperature for the development of fatigue. Thermotolerance is a process that involves increased resilience to an otherwise lethal heat stress that follows a sublethal exposure to heat. Thermotolerance is believed to be the result of increased content of heat shock proteins (Hsp), specially a member of the 70 kDa family, Hsp72 kDa. In humans, we and others have reported that heat acclimation increases intracellular Hsp72 levels. This increase in intracellular Hsp72 could improve whole-body organism thermotolerance by maintaining intestinal epithelial tight junction barriers, by increasing resistance to gut-associated endotoxin translocation, or by reducing the inflammatory response. In this review, we will initially provide an overview of the physiological adaptations induced by heat acclimation and emphasize the main cellular changes that occur with heat acclimation associated with intracellular accumulation of Hsp72. Finally, we will present an argument for a role of whole-body heat acclimation in augmenting cellular thermotolerance, which may protect vital organs from deleterious effects of heat stress in humans.

The Effect of Different Water Immersion Temperatures on Post-Exercise Parasympathetic Reactivation

Purpose We evaluated the effect of different water immersion (WI) temperatures on post-exercise cardiac parasympathetic reactivation. Methods Eight young, physically active men participated in four experimental conditions composed of resting (REST), exercise session (resistance and endurance exercises), post-exercise recovery strategies, including 15 min of WI at 15°C (CWI), 28°C (TWI), 38°C (HWI) or control (CTRL, seated at room temperature), followed by passive resting. The following indices were assessed before and during WI, 30 min post-WI and 4 hours post-exercise: mean R-R (mR-R), the natural logarithm (ln) of the square root of the mean of the sum of the squares of differences between adjacent normal R–R (ln rMSSD) and the ln of instantaneous beat-to-beat variability (ln SD1). Results The results showed that during WI mRR was reduced for CTRL, TWI and HWI versus REST, and ln rMSSD and ln SD1 were reduced for TWI and HWI versus REST. During post-WI, mRR, ln rMSSD and ln SD1 were reduced for HWI versus REST, and mRR values for CWI were higher versus CTRL. Four hours post exercise, mRR was reduced for HWI versus REST, although no difference was observed among conditions. Conclusions We conclude that CWI accelerates, while HWI blunts post-exercise parasympathetic reactivation, but these recovery strategies are short-lasting and not evident 4 hours after the exercise session.

Hydration, thermoregulation, and performance effects of two sport drinks during soccer training sessions

Siegler, JC, Mermier, CM, Amorim, FT, Lovell, RJ, McNaughton, LR and Robergs, RA. Hydration, thermoregulation, and performance effects of two sport drinks during soccer training sessions. J Strength Cond Res 22(5): 1394-1401, 2008-In the present study, we aimed to compare the thermoregulatory response and soccer-specific training performance aspects of two commercially available sport drinks, both of similar carbohydrate concentration, but one containing 5.2% glycerol. Ten players participated in two similar outdoor training sessions and were randomly assigned to each of two drinks: a carbohydrate (C) beverage or a carbohydrate-glycerol (CG) beverage. Players consumed 500 mL of C or CG 30 minutes pre-exercise and at half-time. Pre- and postexercise body mass, core temperature (CT), and heart rate (HR) were recorded, and urine and blood samples were taken. No difference was observed between days for wet bulb globe temperature (session 1: 17.0 ± 1.1°C, session 2: 16.9 ± 1.1°C; P = 0.944). The degree of dehydration (% Δ BM) was greater after the C trial (P = 0.041). Similarly, percent change in plasma volume was greater in the C trial (P = 0.049). No overall main affect was observed between CT and mean exercise HRs during either training session (CT: P = 0.350; mean HR: P = 0.256), and there was no difference observed between groups in time to failure during the session-ending fatigue test (P = 0.547). Ingestion of a CG beverage provided players with better hydration than C alone. However, if training sessions are short (<75 minute), with adequate time for recovery, both drinks are sufficient for maintaining performance intensities during soccer-specific training.

The effect of insulin resistance and exercise on the percentage of CD16+ monocyte subset in obese individuals

Obesity is a low‐grade chronic inflammation condition, and macrophages, and possibly monocytes, are involved in the pathological outcomes of obesity. Physical exercise is a low‐cost strategy to prevent and treat obesity, probably because of its anti‐inflammatory action. We evaluated the percentage of CD16− and CD16+ monocyte subsets in obese insulin‐resistant individuals and the effect of an exercise bout on the percentage of these cells. Twenty‐seven volunteers were divided into three experimental groups: lean insulin sensitive, obese insulin sensitive and obese insulin resistant. Venous blood samples collected before and 1 h after an aerobic exercise session on a cycle ergometer were used for determination of monocyte subsets by flow cytometry. Insulin‐resistant obese individuals have a higher percentage of CD16+ monocytes (14.8 ± 2.4%) than the lean group (10.0 ± 1.3%). A positive correlation of the percentage of CD16+ monocytes with body mass index and fasting plasma insulin levels was found. One bout of moderate exercise reduced the percentage of CD16+ monocytes by 10% in all the groups evaluated. Also, the absolute monocyte count, as well as all other leukocyte populations, in lean and obese individuals, increased after exercise. This fact may partially account for the observed reduction in the percentage of CD16+ cells in response to exercise. Insulin‐resistant, but not insulin‐sensitive obese individuals, have an increased percentage of CD16+ monocytes that can be slightly modulated by a single bout of moderate aerobic exercise. These findings may be clinically relevant to the population studied, considering the involvement of CD16+ monocytes in the pathophysiology of obesity. Copyright

Impaired orthostatic response in patients with type 2 diabetes mellitus after 48 hours of bed rest

OBJECTIVE To compare the effect of bed rest on orthostatic responses of patients with type 2 diabetes mellitus and nondiabetic control subjects. METHODS Six patients with type 2 diabetes and 6 non-diabetic control subjects underwent 48 hours of bed rest and 48 hours of ambulatory activity in randomized order. A 10-minute tilt test was conducted before and after each period of hospitalization, and cardiovascular responses to 80 degrees head-up tilt were analyzed with use of a 2-factorial (study group and bed rest condition) analysis of variance design. We hypothesized that patients with diabetes would experience more severe changes in orthostatic response after bed rest. RESULTS No significant differences in orthostatic responses were observed before bed rest between control subjects and patients with diabetes. After bed rest, control subjects had a greater (P = .01) increase in heart rate during tilt in comparison with before bed rest (before versus after bed rest, 9 +/- 4 versus 24 +/- 7 beats/min) and maintained their blood pressure during tilt. After bed rest, patients with diabetes did not have a compensatory increase in heart rate and had a greater (P = .02) decline in systolic blood pressure during tilt in comparison with before bed rest (before versus after bed rest, -7 +/- 10 versus -21 +/- 11 mm Hg). Their arm and leg skin vasomotor responses (laser Doppler flowmetry) during tilt were not altered after bed rest and were similar to those in control subjects before and after bed rest. CONCLUSION Cardiac neuropathy in patients with type 2 diabetes may prevent a compensatory heart rate response after bed rest deconditioning and result in a more severe orthostatic response. A greater decrease in blood pressure with upright tilt is evident after a relatively short period of bed rest.

Metabolic effects of 2 days of strict bed rest.

OBJECTIVE To examine the possibility of whether 2 days of strict hospitalized bed rest would alter the metabolic profile (including insulin resistance as calculated by the quantitative insulin sensitivity check index or QUICKI) in both normal subjects and patients with type 2 diabetes in comparison with 2 days of normal activity. METHODS The design of this pilot study was a randomized, crossover protocol that evaluated the effects of strict bed rest versus normal activity in 5 healthy normal subjects and 5 healthy patients with type 2 diabetes. All study participants completed a screening visit for assessment of baseline health. RESULTS All 10 study subjects completed the protocol without adverse events. Fasting plasma glucose, insulin, and C-peptide levels as well as several known risk factors for atherosclerosis were unchanged in both the subjects without diabetes and the patients with type 2 diabetes after 2 days of hospitalized bed rest. Insulin resistance demonstrated no significant change during the 48 hours of bed rest when compared with the mean value at baseline. CONCLUSION This study demonstrates that 48 hours of bed rest has no significant effect on insulin resistance or standard metabolic variables in normal subjects and patients with type 2 diabetes. Therefore, achieving good glucose control in patients hospitalized for a period of 2 days or less does not necessitate early ambulation to prevent an increase in insulin resistance.

Heat Shock Protein and Inflammation

Heat Shock Proteins (HSP) are important modulators of both anti-inflammatory and pro-inflammatory responses. In this chapter, we address this apparent paradox by focusing on the effects of the highly heat inducible Hsp70 and its transcription machinery. This transcription machinery may exert important effects on inflammation through pathways, which are independent of heat shock proteins. We then discuss disease states where the balance between the anti-inflammatory and pro-inflammatory effectors is critical to disease outcome

Lymphocyte Redox Imbalance and Reduced Proliferation after a Single Session of High Intensity Interval Exercise.

This study investigated whether an acute session of high-intensity interval training (HIIT) is sufficient to alter lymphocyte function and redox status. Sixteen young healthy men underwent a HIIT session on a cycloergometer, consisting of eight bouts of 1 min at 90–100% of peak power, with 75 seconds of active recovery at 30 W between bouts. Venous blood was collected before, immediately after, and 30 minutes after the HIIT session. In response to Staphylococcus aureus superantigen B (SEB) stimulation, lymphocyte proliferation decreased and the IL-2 concentration increased after the HIIT session. However, the HIIT session had no effect on lymphocyte proliferation or IL-2 response to phytohemagglutinin stimulation. The HIIT session also induced lymphocyte redox imbalance, characterized by an increase in the concentration of thiobarbituric acid reactive substances and a decrease in the activity of the antioxidant enzyme catalase. Lymphocyte viability was not affected by the HIIT session. The frequencies of CD25+ and CD69+ T helper and B lymphocytes in response to superantigen stimulation were lower after exercise, suggesting that superantigen-induced lymphocyte activation was reduced by HIIT. However, HIIT also led to a reduction in the frequency of CD4+ and CD19+ cells, so the frequencies of CD25+ and CD69+ cells within the CD4 and CD19 cell populations were not affected by HIIT. These data indicate that the reduced lymphocyte proliferation observed after HIIT is not due to reduced early lymphocyte activation by superantigen. Our findings show that an acute HIIT session promotes lymphocyte redox imbalance and reduces lymphocyte proliferation in response to superantigenic, but not to mitogenic stimulation. This observation cannot be explained by alteration of the early lymphocyte activation response to superantigen. The manner in which lymphocyte function modulation by an acute HIIT session can affect individual immunity and susceptibility to infection is important and requires further investigation.