Adiponectin, Leptin and Visfatin in Hypoxia and its Effect for Weight Loss in Obesity

Rationale: Hypoxia induces leptin gene expression in human adipocytes via hypoxia-inducible factors (HIF-α/β). Under ambient moderate hypoxia, leptin in adipocytes is elevated for at least 14 days. Leptin is supposedly involved in the reduced food intake, increased utilization of fatty acids for energy production and possible weight loss observed at high altitudes. Literature on adiponectin and visfatin in high altitude is inconsistent with reports of elevated levels and non-elevated levels. Exercise in hypoxia studies in obese subjects have shown a significant weight loss after up to 3 weeks, but it is unclear if this effect holds up for longer time periods. Therefore, we aimed to investigate 32 obese subjects completing 52 exercise and rest sessions within 8 months at either moderate or sham hypoxia and to analyze leptin, adiponectin, and visfatin mRNA-expression at different time points of exposure.Methods: Abdominal subcutaneous fat biopsies were taken from 32 obese subjects before, after 3 months and after 8 months of intervention. Subjects were randomly divided into two groups and exercised at moderate intensity at two different study sites twice a week. The IG was exposed to normobaric hypoxia (FiO2: 14.0 ± 0.2%,) at exercise and at rest (FiO2: 12.0 ± 0.2%) and the CG to sham hypoxia. Quantitative real-time polymerase chain reaction (qPCR) was used in order to determine mRNA-levels of leptin, adiponectin, and visfatin.Results: No differences in leptin levels after 3 and 8 months compared to baseline and between groups were found. There was no significant difference regarding adiponectin or visfatin at any time point compared to baseline in the hypoxia group, but an increase after 3 months was seen in the control group at normoxia compared to the hypoxia group (adiponectin: p = 0.029 and visfatin: p = 0.014).Conclusion: In this first several months' duration randomized sham controlled hypoxia exercise and rest study with obese subjects, we found no time extended leptin mRNA-expression in subjects under hypoxia after 3 and 8 months compared to baseline levels. Moderate exercise in normoxia not in hypoxia leads to elevated adiponectin and visfatin levels after 3 months

Low intense physical exercise in normobaric hypoxia leads to more weight loss in obese people than low intense physical exercise in normobaric sham hypoxia

Training in mild to moderate hypoxia (14–17% O2 in breathing air) and extended resting in moderate hypoxia (9–13% O2) have been shown to have effects in animals and humans on lipid and glucose metabolism, appetite loss, and, in part, on body weight. The causality for these effects is not yet known in detail, and the available data in humans from high-altitude and low-pressure chamber studies are scarce. New technical developments by German companies in the production of artificial climates with normobaric hypoxic conditions in larger rooms at reasonable energy costs allow now to perform hypoxia weight loss studies in obese humans with stable experimental conditions and protocols with a sham hypoxia control. Thirty-two obese people were recruited for a mild intense training study in normobaric hypoxia (15 vol.% O2) and normoxia/sham hypoxia (20.1 vol.% O2). Twenty of these [mean age 47.6 years, mean body mass index (BMI) 33.1, 16 m, 4 f) were willing to follow up on an 8-week, three times per week, 90-min low intense physical exercise in their individual fat burning mode, which has been determined by an exercise testing with spiro-ergometry upfront. The subjects were evenly randomized into a hypoxia and sham hypoxia group. The difference of the two groups in weight loss and changes in HBa1C values were analyzed before and after the training period. No nutritional diet was applied. Subjects in the hypoxia group in mean lost significantly more weight than in the sham hypoxia group (Δ1.14 kg vs Δ0.03 kg; p = 0.026). This resulted in a tendency to reduce the BMI more in the hypoxia group (p = 0.326). In the mean, there was no HbA1C exceeding normal values (mean 5.67 and 5.47%), and the HbA1C stayed basically unchanged after the 8-week training. Mild physical exercise three times per week for 90 min in normobaric hypoxia for 8 weeks led to significantly greater weight loss in obese persons than the exercise in sham hypoxia in this, to our knowledge, first sham hypoxia controlled study

Expiratory Peak Flow and Minute Ventilation Are Significantly Increased at High Altitude versus Simulated Altitude in Normobaria

Simulated altitude (normobaric hypoxia, NH) is used to study physiologic hypoxia responses of altitude. However, several publications show differences in physiological responses between NH and hypobaric conditions at altitude (hypobaric hypoxia, HH). The causality for these differences is controversially discussed. One theory is that the lower air density and environmental pressure in HH compared to NH lead to lower alveolar pressure and therefore lower oxygen diffusion in the lung. We hypothesized that, if this theory is correct, due to physical laws (Hagen-Poiseuille, Boyle), resistance respectively air compression (Boyle) at expiration should be lower, expiratory flow higher, and therefore peak flow and maximum expiratory flow (MEF) 75–50 increased in hypobaric hypoxia (HH) vs. normobaric hypoxia (NH). To prove the hypothesis of differences in respiratory flow as a result of lower alveolar pressure between HH and NH, we performed spirography in NH at different simulated altitudes and the corresponding altitudes in HH. In a cross over study, 6 healthy subjects (2 f/4 m, 28.3 ± 8.2 years, BMI: 23.2 ± 1.9) performed spirography as part of spiroergometry in a normobaric hypoxic room at a simulated altitude of 2800 m and after a seven-hour hike on a treadmill (average incline 14%, average walking speed 1.6 km/h) to the simulated summit of Mauna Kea at 4200 m. After a two-month washout, we repeated the spirometry in HH on the start and top of the Mauna Kea hiking trail, HI/USA. Comparison of NH (simulated 4200 m) and HH at 4200 m resulted in increased pulmonary ventilation during exercise (VE) (11.5%, p < 0.01), breathing-frequency (7.8%, p < 0.01), peak expiratory flow PEF (13.4%, p = 0.028), and MEF50 (15.9%, p = 0.028) in HH compared to NH, whereas VO2max decreased by 2%. At 2800 m, differences were only trendy, and at no altitude were differences in volume parameters. Spirography expresses higher mid expiratory flows and peak flows in HH vs. NH. This supports the theory of lower alveolar and small airway pressure due to a lower air density resulting in a lower resistance

Endurance Training in Normobaric Hypoxia Imposes Less Physical Stress for Geriatric Rehabilitation

Rationale: Evidence suggests that training in hypoxia can be very effective even while requiring less physical effort. We therefore aimed to measure the effect of endurance training under hypoxic conditions on pulmonary and cardiovascular parameters in an elderly population undergoing inpatient rehabilitation. Methods: Forty patients over age 65 years with multiple co-morbid conditions were recruited during a 3-week stay in a geriatric rehabilitation center. Using a randomized, single-blinded, placebo-controlled design, patients were assigned to a hypoxic (HG) or normoxic (NG) group. HG patients completed seven training sessions of 30 min duration on a treadmill in a normobaric chamber with inspired oxygen fraction (FiO2) of 15.27%, with 10-30 min active training. Training was conducted with target heart rate at 80% of peak oxygen consumption (VO2-peak). NG group performed similar training in sham hypoxia (room air or FiO2 = 20.94%). At pre- and post-test completion, measures included: (1) cycle ergometry with ECG monitoring and measurement of VO2-peak, and (2) echocardiography for ejection fraction. Results: The physical effort required of patients to reach target heart rate was reduced significantly (-28%, p = 0.043) in the HG compared to NG. Cardiopulmonary parameters showed no differences between groups. Conclusion: Endurance training at 3,000 meters elevation imposes less stress on the locomotor systems while resulting in a similar physiological strain (i.e., heart rate). Hypoxic training holds promise for successful geriatric rehabilitation by being more accommodating to physical limitations in geriatric patients. Trial registration: Registration at DRKS. (Approval No. 359/12, Trial No. DRKS00005241).(VLID)3081000Version of recor

Weight Loss and Fat Metabolism during Multi-Day High-Altitude Sojourns: A Hypothesis Based on Adipocyte Signaling

Several publications and random observations have reported weight loss in high-altitude sojourners of both sexes. This could be a result of multiple adaptations, which hypoxia and mountaineering provoke on a cellular and organic level. Several publications have discussed the effect on appetite-regulating hormones to be one of the main contributing factors. We aimed to review the available data and show the current state of knowledge regarding nutritional aspects in high altitude with a special focus on fatty dietary forms. To reach this aim we conducted a literature search via PubMed according to the PRISMA 2020 protocol to identify relevant studies. We found that very few studies cover this field with scientifically satisfying evidence. For final analysis, reviews as well as papers that were not clearly related to the topic were excluded. Six articles were included discussing hormonal influences and the impact of exercise on appetite regulation as well as genetic factors altering metabolic processes at altitude. Leptin expression seems to be the biggest contributor to appetite reduction at altitude with an initial increase followed by a decrease in the course of time at high altitude. Its expression is greatly dependent on the amount of white adipose tissue. Since the expression of leptin is associated with an increased β-oxidation of fatty acids, a high-fat diet could be advantageous at a certain time point in the course of high-altitude sojourns