Hypoxic Exercise Training Research Articles

Aerobic Exercise Training Under Normobaric Hypoxic Conditions to Improve Glucose and Lipid Metabolism in Overweight and Obese Individuals: A Systematic Review and Meta-Analysis.

Guo, Hai, Linjie Cheng, Dilihumaier Duolikun, and Qiaoling Yao. Aerobic exercise training under normobaric hypoxic conditions to improve glucose and lipid metabolism in overweight and obese individuals: a systematic review and meta-analysis. High Alt Med Biol. 24:312-320, 2023. Background: Obesity is a critical public health issue around the world, reaching epidemic proportions in some countries. However, only a few studies have examined the effects of hypoxic training on metabolic parameters in an obese population. This systematic review and meta-analysis aimed to determine the effects of aerobic exercise training under normobaric hypoxic conditions versus normoxic training in improving glucose and lipid metabolism in obese individuals. Methods: A systematic search of PubMed, EMBASE, Web of Science, and Wan Fang databases (up to August 2021) was performed to identify randomized controlled trials (RCTs) of overweight or obese human subjects eligible for inclusion. Main study endpoints were changes in body mass index (BMI), waist/hip (W/H) ratio, leptin, blood glucose and insulin levels, as well as blood lipids between hypoxic and normoxic conditioning. Results: Fourteen RCTs with a total of 413 subjects qualified for inclusion. Pooled analyses revealed that BMI (d = 0.38), W/H ratio (d = 0), blood glucose (d = 0.01), and triglyceride (d = -2.27) were not significantly different between aerobic exercise training under hypoxic and normoxic conditions. However, significant differences were found in heart rate at rest (d = -4.50) between aerobic exercise training under hypoxic versus normoxic conditions. Conclusions: In conclusion, no significant benefits were noted in aerobic exercise training under hypoxic conditions over normoxic conditions in overweight or obese individuals. However, the maximum training heart rate mm was significantly higher under hypoxic conditions than under normoxic conditions. Future studies with larger samples controlling for exercise-related parameters, and addressing the potential modifying effects of level of hypoxia, sex, or age on the role of hypoxic exercise training are warranted. PROSPERO registration number: CRD42020221680.

Effect of 4-week intermittent hypoxic exercise training for repeated vertical jump performance in untrained males.

To be successful in sports, it is critical to maintain a high level of muscular power throughout a game. Physiological adaptations induced by hypoxic exercise training would provide benefits for fatigue-resisting ability during repeated explosive exercise. The aim of this study was to determine whether a 4-week intermittent hypoxic exercise training program is more effective in improving power endurance during repeated vertical jumps (VJs) when compared with a normoxic counterpart. Eighteen young adult males were divided into two training groups: 1) normoxic training group (NT, FiO<inf>2</inf>: 20.9%, N.=9); and 2) hypoxic training group (HT, FiO<inf>2</inf>: 13.7%, N.=9). For both NT and HT, participants performed three sessions per week for four weeks. Each session consisted of a 60-min exercise session including strength and power training. A repeated VJ (40 reps/set, 2 sets with 5 min rest given between them) was performed before and after the training (pretraining and post-training). The HT group displayed an improvement in repeated VJ performance in a later phase of set 1 following the training (25-30 rep: pretraining 26.49±6.20 vs. post-training 30.55±5.37cm, P=0.0285; 30-35 rep: pretraining 25.08±5.29 vs. post-training 29.56±5.37cm, P=0.0064; 35-40 rep: pretraining 25.05±5.51 vs. post-training 29.28±5.71cm, P=0.0161). In set 2, repeated VJ performance in the later phase was also enhanced in HT following the training (P<0.05 for all). No changes in repeated VJ performance were seen in NT following the training (P>0.05 for all). Also, the HT group showed a trend towards a decrease in Fatigue Index in set 1 (pretraining 23.51±13.27 vs. Post 11.87±12.51%, P=0.1308) and set 2 (pretraining 29.11±13.66 vs. post-training 17.81±17.97%, P=0.1588) following the training. Hypoxic exercise training can be an effective training modality to improve fatigue-resisting ability during repeated explosive exercise.

Intermittent hypoxic exposure and exercise training positively affect body composition and energy substrate utilization in high-fat diet-induced obese mice

Obesity is considered a major risk factor for increasing insulin resistance and inducing type 2 diabetes. Exercise is known to be the most effective treatment for improving obesity and insulin resistance through body fat loss. Furthermore, hypoxic exposure is known to increase carbohydrate oxidation and improve overall energy expenditure. Therefore, in this study, the effect of combined treatment of exercise and intermittent hypoxia on body composition and metabolic improvement was investigated after inducing obesity through a high-fat diet.The male 5-week-old ICR mice consumed high-fat diet for 7 weeks and were fed ad libitum. After 7 weeks, all groups were randomly divided into 4 groups: CN (sedentary; non-trained), HP (hypoxic exposure; non-trained), EX (trained), and HE (hypoxic exposure and trained). The HP and HE were only exposed hypoxia condition (12% oxygen concentration) for during light phase to coincide with the mouse inactive cycle. The EX and HE conducted treadmill training with 5 times a week for 4 weeks, and the exercise intensity was 70 % of VO2 max. After 4 weeks, the resting metabolic rate (RMR) was measured for all groups through respiratory gas. Then, all mice conducted dual energy X-ray absorptiometry to determine body composition.In body composition results, long-term exercise treatment showed a significantly decrease in fat mass and a significant increase in lean mass. In addition, in the HE, had significantly lower body fat mass and significantly higher lean mass than the EX. Furthermore, in the RMR results, it was investigated that overall energy expenditure increased through an increase in VO2 and VCO2 in the exercise group. However, in the HE, it was confirmed that carbohydrate oxidation at rest was significantly higher than that of the EX. In addition, it was confirmed that fasting blood glucose and HOMA-IR, an indicator of insulin resistance, were also significantly improved in the HE than in the EX.In summary, these results demonstrated that long-term exercise training decrease fat mass and increase in lean mass in high-fat diet-induced obese mice. In addition, it was confirmed that the HE, which intermittent hypoxic exposure combined treatment with exercise, significantly improved body composition compared to the EX, as well as improved carbohydrate oxidation at rest, fasting blood glucose, and HOMA-IR. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Hypoxic Exercise Training Elevates Erythrocyte Aggregation

Pathological erythrocyte aggregation reduces capillary perfusion and oxygen transfer to tissue, which is determined by the negative surface charge on the erythrocyte membrane (intrinsic aggregability) and fibrinogen–erythrocyte interaction (extrinsic factor). Exercise-induced oxidative stress is important for rheological adaptation to training but may also cause erythrocyte senescence. This study clarifies the effects of hypoxic exercise training on intrinsic/extrinsic factors of aggregation. In total, 60 healthy sedentary males were randomly assigned to either hypoxic (HE; FIO2 = 0.15) or normoxic exercise training (NE; FIO2 = 0.21) groups for 30 min·d−1, 5 d·wk−1 for 6 weeks at 60 % of the maximum work rate or to a control group (CTL). A hypoxia exercise test (HET, FIO2 = 0.12) was performed before and after the intervention. Erythrocyte aggregation was assessed by ektacytometry, and fibrinogen binding affinity and senescence biomarkers were assessed by flow cytometry. An acute 12% oxygen HET significantly enhanced erythrocyte global aggregation through intrinsic aggregability. Resting aggregation is promoted by both intrinsic aggregability and fibrinogen binding probability and force after HE, whereas NE is mainly associated with ameliorated fibrinogen–erythrocyte interactions. The HET still facilitated global aggregation after HE because of the augmented fibrinogen-related factors, even though the intrinsic factor was suppressed. Additionally, HE further increased reticulocyte counts while reducing the expression of CD47 and CD147. Resting aggregability is promoted by both intrinsic and extrinsic factors after HE, whereas NE is mainly associated with an ameliorated affinity for fibrinogen. Although an accelerated turnover rate was observed, HE further led to erythrocyte senescence.

Acute exercise-induced changes in cardiac function relates to right ventricular remodeling following 12-wk hypoxic exercise training.

Repeated ventricular exposure to alterations in workload may relate to subsequent cardiac remodeling. We examined whether baseline acute changes in right (RV) and left ventricular (LV) function relate to chronic cardiac adaptation to 12-wk exercise training. Twenty-one healthy individuals performed 12-wk high-intensity endurance running training under hypoxia (fraction of inspired oxygen: 14.5%). Resting transthoracic echocardiography was performed before and after the training program to assess ventricular structure, function, and mechanics (including strain-area/volume loops). In addition, we examined systolic cardiac function during recumbent exercise under hypoxia at baseline (heart rate of 110-120 beats/min, "stress echocardiography"). Fifteen individuals completed training (22.0 ± 2.4 yr, 10 males). Hypoxic exercise training increased RV size, including diameter and area (all P < 0.05). With exception of an increase in RV fractional area change (P = 0.03), RV function did not change post-training (all P > 0.05). Regarding the RV strain-area loop, lower systolic and diastolic slopes were found post-training (P < 0.05). No adaptation in LV structure, function, or mechanics was observed (all P > 0.05). To answer our primary aim, we found that a greater increase in RV fractional area change during baseline stress echocardiography (r = -0.67, P = 0.01) inversely correlated with adaptation in RV basal diameter following 12-wk training. In conclusion, 12-wk high-intensity running hypoxic exercise training induced right-sided structural remodeling, which was, in part, related to baseline increase in RV fractional area change to acute exercise. These data suggest that acute cardiac responses to exercise may relate to subsequent RV remodeling after exercise training in healthy individuals.NEW & NOTEWORTHY During exercise, the right ventricle is exposed to a disproportionally higher wall stress than the left ventricle, which is further exaggerated under hypoxia. In this study, we showed that 12-wk high-intensity running hypoxic exercise training induced right-sided structural remodeling, which was, in part, related to baseline cardiac increase in RV fractional area change to acute exercise. These data suggest that acute RV responses to exercise are related to subsequent right ventricular remodeling in healthy individuals upon hypoxic training.

The acute and chronic effects of high-intensity exercise in hypoxia on blood pressure and post-exercise hypotension: A randomized cross-over trial.

Background:Acute exercise leads to an immediate drop in blood pressure (BP), also called post-exercise hypotension (PEH). Exercise in hypoxia is related to additional vasodilation, potentially contributing to more profound PEH. Therefore, we investigated the impact of hypoxia versus normoxia on the magnitude of PEH. Second, we examined whether these changes in PEH relate to the BP-lowering effects of 12-week exercise training under hypoxia.Methods:In this prospective study, 21 healthy individuals (age 22.2 ± 3.0 years, 14 male) performed a 45-minute high-intensity running exercise on 2 different days in a random order, under hypoxia (fraction of inspired oxygen 14.5%) and normoxia (fraction of inspired oxygen 20.9%). BP was examined pre-exercise (t = 0) and at t = 15, t = 30, t = 45, and t = 60 minutes post-exercise. Afterward, subjects took part in a 12-week hypoxic running exercise training program. Resting BP was measured before and after the 12-week training program.Results:Acute exercise induced a significant decrease in systolic BP (systolic blood pressure [SBP], P = .001), but not in diastolic BP (diastolic blood pressure [DBP], P = .113). No significant differences were observed in post-exercise BP between hypoxic and normoxic conditions (SBP, P = .324 and DBP, P = .204). Post-exercise changes in SBP, DBP, and mean arterial pressure significantly correlated to the 12-week exercise training-induced changes in SBP (r = 0.557, P = .001), DBP (r = 0.615, P < .001), and mean arterial pressure (r = 0.458, P = .011).Conclusion:Our findings show that hypoxia does not alter the magnitude of PEH in healthy individuals, whilst PEH relates to the BP-lowering effects of exercise. These data highlight the strong link between acute and chronic changes in BP.

Hypoxic Exercise Training to Improve Exercise Capacity in Obese Individuals

Combining exercise training with hypoxic exposure has been recently proposed as a new therapeutic strategy to improve health status of obese individuals. Whether hypoxic exercise training (HET) provides greater benefits regarding body composition and cardiometabolic parameters than normoxic exercise training (NET) remains, however, unclear. We hypothesized that HET would induce greater improvement in exercise capacity and health status than NET in overweight and obese individuals. Twenty-three subjects were randomized into 8-wk HET (11 men and 1 woman; age, 52 ± 12 yr; body mass index, 31.2 ± 2.4 kg·m) or NET (eight men and three women; age, 56 ± 11 yr; body mass index, 31.8 ± 3.2 kg·m) programs (three sessions per week; constant-load cycling at 75% of maximal heart rate; target arterial oxygen saturation for HET 80%, FiO2 ~0.13, i.e., ~3700 m a.s.l.). Before and after the training programs, the following evaluations were performed: incremental maximal and submaximal cycling tests, measurements of pulse-wave velocity, endothelial function, fasting glucose, insulin and lipid profile, blood NO metabolites and oxidative stress, and determination of body composition by magnetic resonance imaging. Peak oxygen consumption and maximal power output increased significantly after HET only (peak oxygen consumption HET + 10% ± 11% vs NET + 1% ± 10% and maximal power output HET + 11% ± 7% vs NET + 3% ± 10%, P < 0.05). Submaximal exercise responses improved similarly after HET and NET. Except diastolic blood pressure which decreased significantly after both HET and NET, no change in vascular function, metabolic status and body composition was observed after training. Hypoxic exercise training only increased nitrite and reduced superoxide dismutase concentrations. Combining exercise training and hypoxic exposure may provide some additional benefits to standard NET for obese individual health status.

Effect Of Intermittent Hypoxic Exercise Training On Improving Altitude Acclimatization

Effect Of Intermittent Hypoxic Exercise Training On Improving Altitude Acclimatization

PO-070 Effects of hypoxic exercise training on aerobic capacity-related proteins in overweight/obese adult males

Objective Since the Mexican Olympic Games, altitude training has attracted the attention of international sports science circle with its remarkable training effect, which is regarded as one of the effective methods to improve aerobic capacity. With the improvement of altitude training by scholars at home and abroad, hypoxic training has gradually entered the public view. Hypoxic training aims to achieve hypoxic stimulation by artificially simulating the natural hypoxic environment in the plateau or simulating the biological effects of hypoxic on human body. However, whether the aerobic capacity can be improved through hypoxic training requires us to further study and explore the mechanism of hypoxic training. This study explored the mechanism of hypoxic exercise training by stimulating long-term hypoxic exercise training for overweight or obese adult males.&#x0D; Methods In this study, 40 male (aged 18—47 years) overweight/obese subjects were recruited. No physical condition was abnormal after physical examination, and BMI ≥ 24 was overweight, while BMI ≥ 28 was obese. All subjects were paired according to their weight and divided into the hypoxic group and the normoxic group, the exercise intervention lasted for 6 weeks. The exercise intervention program consists of 30min strength training and 30min endurance training, with 5 minutes of warm-up and finishing activities before and after training. Strength training uses dumbbells, chooses 12RM weight, exercise with 8 actions, which are dead lift, upright row, squat, shoulder press, calf Jump, advance junge, biceps curl and triceps extension, each action 2 Group, rest between groups for 30s. Endurance training grade 0°treadmill, speed range according to the target heart rate adjustment, the target heart rate interval computation method for 60% HRmax—70% HRmax. Among them, subjects in the hypoxic group wore inhaled low-oxygen devices, which enabled them to exercise in a hypoxic environment. The oxygen content of the inhaled mixed gas was 16%. The subjects in the aerobic group exercised in an aerobic environment. Nutritional education was administered to all subjects prior to the start of the exercise intervention, but diet was not restricted during the intervention. Fasting venous blood before and after intervention, the detection of hemoglobin (Hb) and erythropoietin (EPO), hypoxia-inducible factor 1 alpha (HIF1α), vascular endothelial growth factor (VEGF) and testosterone (T). All test results are the mean ± standard deviation, data comparison between groups using nonparametric the Mann-Whitney U test, data comparison in the group using nonparametric Wilcoxon match the symbol rank test, the significance level of P&lt;0.05, very significance level of P&lt;0.01.&#x0D; Results (1) After 6 weeks of intervention, Hb levels were elevated in the hypoxic group, but there was no statistically difference compared with the pre-intervention (P&gt;0.05). And the change rate of Hb in the hypoxic group was higher than that in the normoxic group, but there was no statistically significant difference between the subjects (P&gt;0.05).&#x0D; EPO levels were significantly higher in hypoxia group than before intervention (P&lt;0.01). There was no significant change in EPO levels in the normoxic group (P&gt;0.05). The change rate of EPO in the hypoxic group was statistically higher compared with the normoxic group (P&lt;0.05).&#x0D; The level of HIF1α was significantly increased in the hypoxic group (P&lt;0.01), and the change rate of HIF1α in the hypoxic group was statistically higher compared with the normox group (P&lt;0.01).&#x0D; The VEGF level in the hypoxic group was significantly higher than that before the intervention (P&lt;0.05). The change rate of VEGF in the hypoxic group was statistically higher compared with the normoxic group (P&lt;0.01).&#x0D; The T level of the hypoxic group was significantly higher than that before the intervention (P&lt;0.01), and the T level was decreased in the normoxic group, but it was not statistically difference compared with the pre-intervention (P &gt;0.05), the rate of T change in the hypoxic group was statistically significant compared with the normox group (P&lt;0.01).&#x0D; Conclusions 6-week hypoxic exercise training can increase the levels of EPO, HIF1α, VEGF and T in the blood of overweight/obese people.

PO-203 Across generations maternal exercise in hypoxic environment on mitochondrial biosynthetic factors in rat skeletal muscle

Objective Environmental and maternal exercise experienced even during the very earliest stages of life has the potential to cause developmental changes.The growing evidence demonstrated that diverse environmental stressors affect offspring in variousaspects in early stage of lifeand can be transmitted directly or indirectly by both parental lines.The purpose of the present study was to investigate the effect of across generations maternal exercise training under the hypoxic environment on mitochondrial biogenesis and angiogenesis related protein expressions of skeletal muscle in offspring ofmultiple generations.&#x0D; Methods The experimental groups were divided into four groups as NCON (control in normoxia), NEXE (exercise in normoxia), HCON (control under hypoxia), HEXE (exercise under hypoxia), and studied for three generations. Exercise groups were run on animal treadmill at 60%-75% VO2maxfor one hour per day, five times per week for 10 weeks (seven weeks before conception and during conception for three weeks). Animals were sacrificed at a given time table and assayed mitochondrial biogenesis and angiogenesis related protein expressions using western blotting.&#x0D; Results The major findings from the present study were firstly, maternal exercise training before and during conception under hypoxic environment increase in mitochondrial biogenesis and angiogenesis related proteins expressions in both maternal and offspring skeletal muscles, secondly, long term of exposure to hypoxic environment without exercise training increase in mitochondrial biogenesis and angiogenesis related proteins expressions in offspring skeletal muscles, and further increased when exercise training performed at hypoxic environment, lastly, there was no cumulative benefit by consecutively exposure for three generations under hypoxic environment, which is indicating world winning runners from high altitude dwellers may not relay on the duration of sojourn under hypoxic environment, but rather selection and training related factors.&#x0D; Conclusions In summary, maternal exercise training before and during conception under hypoxic environment increase in mitochondrial biogenesis(PGC-1α, COX-Ⅳ, NRF-1, mtTFA) and angiogenesis(HIF-1α, VEGFtotal) related proteins expressions in both maternal and offspring skeletal muscles, especially exercise training stimulated the protein expressions under hypoxic environment than normoxic condition. Therefore, exercise capacity may be endowed by both hypoxic environment and exercise training at hypoxic environment.&#x0D;

Effects of normoxic and hypoxic exercise training on the bactericidal capacity and subsequent apoptosis of neutrophils in sedentary men.

Phagocytosis and oxidative burst are essential mechanisms of innate immunity by which neutrophils eliminate invading pathogens. Afterwards, phagocytic neutrophils are dissipated by facilitating apoptosis to control inflammation. This study investigates how exercise training with or without hypoxic exposure affects the bactericidal activity and subsequent apoptosis of neutrophils following strenuous exercise. A total of 60 healthy, sedentary men were randomly divided into four groups (n = 15 in each group), who were exposed to 21% O2 [normoxic control (NC)] or 15% O2 [hypoxic control (HC)] at rest or were trained at 50% of peak work rate at 21% O2 [normoxic training (NT)] or 15% O2 [hypoxic training (HT)] for 30min/day, 5days/week for 4weeks. Before the intervention, acute strenuous exercise (SE) enhanced the phagocytosis of Escherichia coli (E. coli) by neutrophils and the release of neutrophil oxidant products in response to E. coli, accompanied by increases in the expression of adhesion molecules (CD62L, CD11b, and CD11a), an opsonic receptor (FcγIIIBR), and complement receptors (C1qRp and CD5aR) on neutrophils. Subsequently, the SE facilitated caspase-3 activation and phosphatidylserine exposure in E. coli-stimulated neutrophils. Furthermore, 4 weeks of HT promoted the expressions of adhesion molecules and opsonic/complement receptors on neutrophils, and it also augmented the bactericidal and apoptotic activities of neutrophils at rest or after SE. However, NT, HC, and NC did not influence these neutrophil-related immune responses to strenuous exercise. Therefore, we conclude that the HT regimen effectively promotes the bactericidal capacity of neutrophils, and facilitates their subsequent apoptosis both at rest and following SE.

Exposure and Exercise Training in Hypoxic Conditions as a New Obesity Therapeutic Modality: A Mini Review.

Obesity is an important health problem caused by positive energy balance. Generally, low calorie dietary intake combined with regular exercise is the most common modality to lose bodily fat in obese people. Although this is the first modality of choice for obesity treatment, it needs to be applied to obese patients for at least 12 weeks or more and it does not provide consistent results because it is difficult to suppress increased appetite due to exercise. Recently, many researchers have been applying hypoxic conditions for the treatment of obesity, as many studies show that people residing in high altitudes have a lower percentage of body fat and fewer obesity-related illnesses than people living at sea level. Hypoxic therapy treatment, including hypoxic exposure or hypoxic exercise training, is recommended as a way to treat and prevent obesity by suppression of appetite, increasing basal metabolic rate and fat oxidation, and minimizing side effects. Hypoxic therapy inhibits energy intake and appetite-related hormones, and enhances various cardiovascular and metabolic function parameters. These observations indicate that hypoxic therapy is a new treatment modality for inducing fat reduction and promoting metabolic and cardiovascular health, which may be an important and necessary strategy for the treatment of obesity. As such, hypoxic therapy is now used as a general medical practice for obesity treatment in many developed countries. Therefore, hypoxic therapy could be a new, practical, and useful therapeutic modality for obesity and obesity-related comorbidities.

Effects of Hypoxic Living and Exercise Training on the miR-27/PPARγ Pathway in Obese Rat Liver

Effects of Hypoxic Living and Exercise Training on the miR-27/PPARγ Pathway in Obese Rat Liver

Hypoxic Exercise Training Promotes apelin/APJ Expression in Skeletal Muscles of High Fat Diet-Induced Obese Mice.

Apelin, an endogenous ligand of the G-protein-coupled receptor APJ, is a novel myokine and may play a key role in regulating energy metabolism. The purpose of the present study was to investigate the effects of hypoxic exposure, exercise, and hypoxic exercise training on the expression of apelin and APJ in skeletal muscle of obese mice. Sixty two-months old C57BL/6J mice were randomly divided into two groups: Ten in normal diet group (N) and 50 in the high fat diet (HFD) groups. After two months of feeding, the HFD mice, whose body weight was 20% higher than the average weight of the N group, were selected as obese mice and further allocated into four groups: Control (C), Exercise (E), Hypoxia (H), and Exercise plus Hypoxia (E+H), at 8-9 mice/group. Besides body weight, measured variables in skeletal muscle were protein/mRNA levels of apelin/APJ, AMPKα-Thr172 phosphorylation, hypoxia inducible factor-1α (HIF-1α), mRNA levels of peroxisome proliferator-activated receptor α (PPARα), estrogen-related receptor (ERRα), and nuclear respiratory factor 1 (NRF1). Obese mice had significantly lower mRNA and protein expressions of apelin/ APJ in skeletal muscles than the normal body weight mice. After four weeks of interventions, hypoxic exercise training decreased body weight and increased mRNA and protein expressions of apelin and APJ, mRNA expression of ERRα, and protein expression of HIF-1α. These results indicate that changes of body weight may be associated with the levels of apelin/APJ expressions in skeletal muscle.

Hypoxic Living and Exercise Training Alter Adipose Tissue Leptin/Leptin Receptor in Rats.

Background: Hypobaric hypoxia results in weight loss in obese individuals, and exercise training is advocated for the treatment of obesity and its related metabolic dysfunctions. The purpose of this study was to investigate the effects of hypoxic living and exercise training on obesity and adipose tissue leptin/leptin receptor in dietary-induced obese rats.Methods: One hundred and thirty high-fat diet fed Sprague-Dawley rats were assigned into one of the following groups (n = 10 each): control, sedentary hypoxic living for 1–4 weeks (SH1, SH2, SH3, and SH4), living, and exercise training in normoxic conditions for 1–4 weeks (TN1, TN2, TN3, and TN4), and living and exercise training in hypoxic conditions for 1–4 weeks (TN1, TN2, TN3, and TN4). Epididymal adipose tissue expression levels of leptin and leptin receptor were determinedResults: Compared to hypoxic living and living and exercise training in normoxic conditions, living and exercise training in hypoxic conditions for 3–4 weeks resulted in lower Lee index (P < 0.05–0.01), and higher expression of leptin and leptin receptor (P < 0.05–0.01) in adipose tissue.Conclusion: In a rodent model of altitude training, living, and exercise training in hypoxic conditions resulted in greater alterations in obesity and adipose tissue leptin/leptin receptor than hypoxic living alone and living and exercise training in normoxic conditions.

Effects of hypoxic exercise training on microRNA expression and lipid metabolism in obese rat livers.

To investigate the effects of hypoxic exercise training on microRNA (miRNA) expression and the role of miRNA expression in regulating lipid metabolism, 20 dietary-induced obese SD rats were divided into a normoxic sedentary group (N, n=10) and a hypoxic exercise training group (H, n=10). After four weeks, measurements were taken of body weight, body length, fat mass, serum lipid concentration, miRNAs differentially expressed in rat liver, and gene and protein expression levels of peroxisome proliferator activated receptor α (PPARα), fatty acid synthetase (FAS), and carnitine palmitoyl transferase 1A (CPT1A) in rat liver. Body weight, Lee's index, fat mass, fat/weight ratio, and serum levels of total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) were all significantly lower in the H group than in the N group (P<0.01). Six miRNAs expressed significantly differently in the liver (P<0.05). Specifically, expression levels of miR-378b were significantly lower in the H group than in the N group (P<0.05). Compared with the normoxic sedentary group, hypoxic exercise training resulted in a lower ratio of FAS mRNA to CPT1A mRNA (P<0.05), as well as lower CPT1A protein levels (P<0.01), while a higher ratio of FAS to CPT1A protein levels (P<0.01) was observed. In conclusion, hypoxic training may elevate the resistance of high fat diet induced obesity in rats by reducing the expression of miR-378b, and decrease the fatty acid mitochondrial oxidation in obese rat livers by decreasing the protein expression of CPT1A and increasing the protein expression ratio of FAS/CPT1A.

Hand temperature responses to local cooling after a 10-day confinement to normobaric hypoxia with and without exercise.

The study examined the effects of a 10-day normobaric hypoxic confinement (FiO2: 0.14), with [hypoxic exercise training (HT); n = 8)] or without [hypoxic ambulatory (HA; n = 6)] exercise, on the hand temperature responses during and after local cold stress. Before and after the confinement, subjects immersed their right hand for 30 min in 8 °C water [cold water immersion (CWI)], followed by a 15-min spontaneous rewarming (RW), while breathing either room air (AIR), or a hypoxic gas mixture (HYPO). The hand temperature responses were monitored with thermocouples and infrared thermography. The confinement did not influence the hand temperature responses of the HA group during the AIR and HYPO CWI and the HYPO RW phases; but it impaired the AIR RW response (-1.3 °C; P = 0.05). After the confinement, the hand temperature responses were unaltered in the HT group throughout the AIR trial. However, the average hand temperature was increased during the HYPO CWI (+0.5 °C; P ≤ 0.05) and RW (+2.4 °C; P ≤ 0.001) phases. Accordingly, present findings suggest that prolonged exposure to normobaric hypoxia per se does not alter the hand temperature responses to local cooling; yet, it impairs the normoxic RW response. Conversely, the combined stimuli of continuous hypoxia and exercise enhance the finger cold-induced vasodilatation and hand RW responses, specifically, under hypoxic conditions.

Hypoxic exercise training improves cardiac/muscular hemodynamics and is associated with modulated circulating progenitor cells in sedentary men

BackgroundCirculating progenitor cells (CPCs) improve cardiovascular function and organ perfusion by enhancing the capacities of endothelial repair and neovasculogenesis. This study investigates whether exercise regimens with/without hypoxia affect cardiac and muscular hemodynamics by modulating CPCs and angiogenic factors. MethodsForty sedentary males were randomly divided into hypoxic (HT, n=20) and normoxic (NT, n=20) training groups. The subjects were trained on a bicycle ergometer at 60%VO2max under 15% (HT) or 21% (NT) O2 conditions for 30min daily, five days weekly for five weeks. ResultsAfter the five-week interventions, the HT group exhibited a larger improvement in aerobic capacity than the NT group. Furthermore, the HT regimen (i) enhanced cardiac output (QH) and perfusion (QM)/oxygenation of vastus lateralis during exercise; (ii) increased levels of CD34+/KDR+/CD117+, CD34+/KDR+/CD133+, and CD34+/KDR+/CD31+ cells in blood; (iii) promoted the proliferative capacity of these CPC subsets, and (iv) elevated plasma nitrite/nitrate, stromal cell-derived factor-1 (SDF-1), matrix metalloproteinase-9 (MMP-9), and vascular endothelial growth factor-A (VEGF-A) concentrations. Despite the lack of changes in QH and the number or proliferative capacity of CD34+/KDR+/CD117+ or CD34+/KDR+/CD31+ cells, the NT regimen elevated both QM and plasma nitrite/nitrate levels and suppressed the shedding of endothelial cells (CD34−/KDR+/phosphatidylserine+ cells). ConclusionsThe HT regimen improves cardiac and muscular hemodynamic adaptations, possibly by promoting the mobilization/function of CPCs and the production of angiogenic factors.

Effect of different methods of hypoxic exercise training on free radical oxidation and antioxidant enzyme activity in the rat brain

The effects of different modes of hypoxic exercise training on free radical production and antioxidant enzyme activity in the brain of rats were investigated in this study. A total of 40 healthy 2-month-old male Wister rats were randomly assigned to 5 groups according to different training modes. Endurance training sessions were performed for 5 weeks under different normoxic (atmospheric pressure ~632 mmHg, altitude ~1,500 m) and hypoxic conditions (atmospheric pressure ~493 mmHg, altitude ~3,500 m) at the same relative intensity. The superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activity and the malondialdehyde (MDA) content of the brain were evaluated by spectrophotometric analysis. Compared to the low-training low (LL) group, the SOD activity was significantly increased by 68.73, 54.28 and 304.02% in the high-training high (HH), high-training low (HL) and high-exercise high-training low (HHL) groups, respectively. However, no obvious change was observed for the low-training high (LH) group. In comparison to the LL group, the GSH-Px activity was found to be significantly higher in the HH, HL, LH and HHL groups. Similarly, in comparison to the LL group, the CAT activity exhibited a significant increase in the HH, HL, LH and HHL groups. Compared to the LL group, the MDA content was significantly increased in the HH, HL and HHL groups, although no significant difference was detected for the LH group. Following exhaustive exercise, the antioxidant enzyme activities in the rat brains were immediately improved in all the hypoxia modes. Moreover, the free radical production was increased after all the modes of hypoxic exercise training, with the LH mode being the only exception.

Absolute hypoxic exercise training enhancesin vitrothrombin generation by increasing procoagulant platelet-derived microparticles under high shear stress in sedentary men

HS (high shear) stress associated with artery stenosis facilitates TG (thrombin generation) by increasing the release of procoagulant PDMPs (platelet-derived microparticles). Physical exercise and hypoxia may paradoxically modulate vascular thrombotic risks. The aim of the present study was to investigate how exercise training with/without hypoxia affected TG mediated by PDMPs under physio-pathological shear flows. A total of 75 sedentary males were randomly divided into five groups (n=15 in each group): 21% O2 [NC (normoxic control)] or 15% O2 [HC (hypoxic control)] at rest or were trained at 50% of peak work rate under 21% O2 [NT (normoxic training)] or 15% O2 [HAT (hypoxic-absolute training)], or 50% of HR (heart rate) reserve under 15% O2 [HRT (hypoxic-relative training)] for 30 min/day, 5 days/week for 4 weeks. The PDMP characteristics and dynamic TG were measured by flow cytometry and thrombinography respectively. Before the intervention, strenuous exercise markedly increased the PDMP count (14.8%) and TG rate (19.5%) in PDMP-rich plasma at 100 dynes/cm2 of shear stress (P<0.05). After the interventions, both NT and HRT significantly attenuated the enhancement of HS-induced PDMPs (4.7 and 4.9%) and TG rate (3.8 and 3.0%) (P<0.05) by severe exercise. Conversely, HAT notably promoted the PDMP count (37.3%) and TG rate (38.9%) induced by HS (P<0.05), concurrent with increasing plasma TF (tissue factor) and coagulation factor V levels at rest or following exercise. We conclude that both HRT and NT depress similarly HS-mediated TG during exercise, but HAT accelerates the prothrombotic response to vigorous exercise. These findings provide new insights into how exercise training under a hypoxic condition influences the risk of thrombosis associated with stenotic arteries.