Chronic intermittent hypobaric hypoxia protects vascular endothelium by ameliorating autophagy in metabolic syndrome rats

Cui, Fang; Guan, Yue; Guo, Jing; Tian, Yanming; Hu, Haofei; Zhang, Xiangjian; Zhang, Yi

doi:10.1016/j.lfs.2018.05.008

Cited by 16 publications

(9 citation statements)

References 30 publications

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“…The rats were randomly divided into CIHH treatment (CIHH) and control groups after bone fracture surgery. As previously described ( 33 , 34 ), the rats in the CIHH group were exposed to a hypobaric hypoxia chamber (Pressure: 50 kPa, oxygen concentration: 10%-11%, 22°C ± 1°C) for 6 continuous hours (from 10:100 to 16:00) every day, and the rest time was kept in normal conditions. The control rats were housed under normal conditions.…”

Section: Methodsmentioning

confidence: 99%

Chronic Intermittent Hypobaric Hypoxia Enhances Bone Fracture Healing

et al. 2021

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The effect of chronic intermittent hypobaric hypoxia (CIHH) on bone fracture healing is not elucidated. The present study aimed to investigate the role of CIHH on bone fracture healing and the mechanism. The Sprague-Dawley rats were randomly divided into the CIHH group and control group and monitored for 2, 4, or 8 weeks after femoral fracture surgery. Bone healing efficiency was significantly increased in the CIHH group as evidenced by higher high-density bone volume fractions, higher bone mineral density, higher maximum force, and higher stiffness. Histologically, the CIHH group exhibited superior bone formation, endochondral ossification, and angiogenic ability compared with the control group. The expression of HIF-1α and its downstream signaling proteins VEGF, SDF-1/CXCR4 axis were increased by the CIHH treatment. Moreover, the expression of RUNX2, osterix, and type I collagen in the callus tissues were also up-regulated in the CIHH group. In conclusion, our study demonstrated that CIHH treatment improves fracture healing, increases bone mineral density, and increases bone strength via the activation of HIF-1α and bone production-related genes.

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Section: Methodsmentioning

confidence: 99%

Chronic Intermittent Hypobaric Hypoxia Enhances Bone Fracture Healing

et al. 2021

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“…MS rats and MS + CIHH rats were fed with high fat diet (24% protein, 12% fat, and 42% carbohydrate; nutrient ratio, specific composition: 8% lard, 2% soy flour, and 90% chow diet) and water supplemented with 10% (wt/vol) fructose. Sixteen weeks later, CIHH and MS + CIHH rats were exposed to hypobaric hypoxia (simulation of 5000 m altitude for 28 days in a hypobaric chamber, 6 h/day, Po 2 = 84 mm Hg), as described in our previous studies (Cui et al, 2018). All animals had free access to water and food and were housed in a temperature-controlled room (22 ± 1 • C) with a 12 h/12 h light/dark cycle.…”

Section: Methodsmentioning

confidence: 99%

“…The protein expression of AMPKα, phosphorylated (p)-AMPKα (Thr172), mTOR, p-mTOR (ser2448), 78KD glucose-regulated protein (GRP78), C/EBP-homologous protein (CHOP), Beclin-1, microtubule associated protein 1 light chain 3 (LC3), p62 was analyzed by Western blotting (Cui et al, 2018). Briefly, hepatic samples (100 mg) were collected and extracted for protein (centrifuged at 12000 rpm, 15 min, 4 • C).…”

Section: Western Blot Analysismentioning

confidence: 99%

“…Chronic intermittent hypobaric hypoxia (CIHH) simulates the plateau environment via low-pressure and low-oxygen conditions. Previous studies have shown that CIHH have beneficial effects on various tissues of the body (Cui et al, 2018;Shi et al, 2015;Tian et al, 2016;Yuan et al, 2015;Zhou et al, 2013), including improving ischemia/reperfusion or hypoxia/reoxygenation induced tissues damage (Zhou et al, 2013); improving endothelial dysfunction and vascular relaxation in mesenteric arteries (Cui et al, 2018); anti-inflammatory effect by reducing the level of collagen-induced arthritis inflammatory factors (Shi et al, 2015); improving fructose induced liver damage by inhibiting ERS (Yuan et al, 2015). However, the effect and mechanisms of autophagy on CIHH inhibiting ERS in the liver of rats, is still unclear.…”

Section: Introductionmentioning

confidence: 99%

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The Effect of Autophagy on Chronic Intermittent Hypobaric Hypoxia Ameliorating Liver Damage in Metabolic Syndrome Rats

Cui

Guo

et al. 2020

Front. Physiol.

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Aim: Our previous study demonstrated that chronic intermittent hypobaric hypoxia (CIHH) can confer hepatic protection by reducing endoplasmic reticulum stress (ERS) in high-fat-high-fructose induced metabolic syndrome (MS) rats. It is known that there is a functional coupling between autophagy and ERS. This study aimed to investigate the effect of CIHH on autophagy function and adenosine mono-phosphate-activated protein kinase-mammalian target of rapamycin (AMPKα-mTOR) signaling pathway in hepatic tissue of MS rats.Main Methods: 6-week old male Sprague-Dawley rats were randomly divided into: control (CON), CIHH (treated with hypobaric hypoxia simulating 5000-m altitude for 28 days, 6 h daily), MS (induced by 16-week high fat diet and 10% fructose water feeding), and MS + CIHH groups (exposed to CIHH after 16-week MS model). Food and water intakes, body weight, Lee's index, fat coefficient, systolic arterial pressure, blood biochemicals, and histopathology of liver were measured, the expression of phosphorylated (p)-AMPK, p-mTOR, autophagy-related and ERS-related proteins were assayed in hepatic tissue.Key Findings: The MS rats displayed obesity, hypertension, polydipsia, glucose and lipids metabolism disorders, increased inflammatory cytokine, hepatic tissue morphological and functional damage, and the up-regulated expressions of ERSrelated, autophagy-related proteins and p-mTOR, and the down-regulated expression of p-AMPKα. All aforementioned abnormalities in MS rats were ameliorated in MS + CIHH rats.Significance: In conclusion CIHH confers hepatic protection through activating AMPK-mTOR signaling pathway and the autophagy function, thus inhibiting ERS in hepatic tissue.Keywords: chronic intermittent hypobaric hypoxia, metabolic syndrome, endoplasmic reticulum stress, autophagy, AMPK-mTOR signaling pathway Frontiers in Physiology | www.frontiersin.org January 2020 | Volume 11 | Article 13 absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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“…Six to seven weeks old male Sprague-Dawley rats (body weight 80–120 g) provided by the Animal Center of Hebei Medical University were randomly divided into chow diet and high-fat-high-fructose diet groups, which were fed with a chow diet and drinking water (containing 22% protein, 4% fat, and 50% carbohydrate; nutrient ratio, specific composition per 1000 g: 99.50 g water, 216.97 g protein, 50.38 g fat, 56.87 g coarse ash, 24.00 g fiber, 13.29 g calcium, 9.17 g phosphorus) and with a high-fat diet and fructose water (containing 24% protein, 12% fat, and 42% carbohydrate; nutrient ratio, specific composition: 8% lard, 2% soy flour and 90% chow diet. 10% (wt/vol) fructose in water) [ 21 ], respectively.…”

Section: Methodsmentioning

confidence: 99%

Chronic intermittent hypobaric hypoxia improves markers of iron metabolism in a model of dietary-induced obesity

Cui

Guo

et al. 2020

J Inflamm

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Background Obesity, a risk factor for many chronic diseases, is a potential independent risk factor for iron deficiency. Evidence has shown that chronic intermittent hypobaric hypoxia (CIHH) has protective or improved effects on cardiovascular, nervous, metabolic and immune systems. We hypothesized that CIHH may ameliorate the abnormal iron metabolism in obesity. This study was aimed to investigate the effect and the underlying mechanisms of CIHH on iron metabolism in high-fat-high-fructose-induced obese rats. Methods Six to seven weeks old male Sprague-Dawley rats were fed with different diet for 16 weeks, and according to body weight divided into four groups: control (CON), CIHH (28-day, 6-h daily hypobaric hypoxia treatment simulating an altitude of 5000 m), dietary-induced obesity (DIO; induced by high fat diet and 10% fructose water feeding), and DIO + CIHH groups. The body weight, systolic arterial pressure (SAP), Lee index, fat coefficient, blood lipids, blood routine, iron metabolism parameters, interleukin6 (IL-6) and erythropoietin (Epo) were measured. The morphological changes of the liver, kidney and spleen were examined. Additionally, hepcidin mRNA expression in liver was analyzed. Results The DIO rats displayed obesity, increased SAP, lipids metabolism disorders, damaged morphology of liver, kidney and spleen, disturbed iron metabolism, increased IL-6 level and hepcidin mRNA expression, and decreased Epo compared to CON rats. But all the aforementioned abnormalities in DIO rats were improved in DIO + CIHH rats. Conclusions CIHH improves iron metabolism disorder in obese rats possibly through the down-regulation of hepcidin by decreasing IL-6 and increasing Epo.

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Chronic intermittent hypobaric hypoxia protects vascular endothelium by ameliorating autophagy in metabolic syndrome rats

Cited by 16 publications

References 30 publications

Chronic Intermittent Hypobaric Hypoxia Enhances Bone Fracture Healing

Chronic Intermittent Hypobaric Hypoxia Enhances Bone Fracture Healing

The Effect of Autophagy on Chronic Intermittent Hypobaric Hypoxia Ameliorating Liver Damage in Metabolic Syndrome Rats

Chronic intermittent hypobaric hypoxia improves markers of iron metabolism in a model of dietary-induced obesity

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