scholarly journals Chronic Intermittent Hypoxia Induces Early-Stage Metabolic Dysfunction Independently of Adipose Tissue Deregulation

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1233
Author(s):  
Fátima O. Martins ◽  
Joana F. Sacramento ◽  
Elena Olea ◽  
Bernardete F. Melo ◽  
Jesus Prieto-Lloret ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Adipose Tissue ◽  
Intermittent Hypoxia ◽  
Early Stage ◽  
Tissue Hypoxia ◽  
Whole Body ◽  
Chronic Intermittent Hypoxia ◽  
Adipose Tissue Dysfunction ◽  
Obstructive Sleep

Several studies demonstrated a link between obstructive sleep apnea (OSA) and the development of insulin resistance. However, the main event triggering insulin resistance in OSA remains to be clarified. Herein, we investigated the effect of mild and severe chronic intermittent hypoxia (CIH) on whole-body metabolic deregulation and visceral adipose tissue dysfunction. Moreover, we studied the contribution of obesity to CIH-induced dysmetabolic states. Experiments were performed in male Wistar rats submitted to a control and high-fat (HF) diet. Two CIH protocols were tested: A mild CIH paradigm (5/6 hypoxic (5% O2) cycles/h, 10.5 h/day) during 35 days and a severe CIH paradigm (30 hypoxic (5% O2) cycles, 8 h/day) during 15 days. Fasting glycemia, insulinemia, insulin sensitivity, weight, and fat mass were assessed. Adipose tissue hypoxia, inflammation, angiogenesis, oxidative stress, and metabolism were investigated. Mild and severe CIH increased insulin levels and induced whole-body insulin resistance in control animals, effects not associated with weight gain. In control animals, CIH did not modify adipocytes perimeter as well as adipose tissue hypoxia, angiogenesis, inflammation or oxidative stress. In HF animals, severe CIH attenuated the increase in adipocytes perimeter, adipose tissue hypoxia, angiogenesis, and dysmetabolism. In conclusion, adipose tissue dysfunction is not the main trigger for initial dysmetabolism in CIH. CIH in an early stage might have a protective role against the deleterious effects of HF diet on adipose tissue metabolism.

scholarly journals Intermittent Hypoxia Mediates Caveolae Disassembly That Parallels Insulin Resistance Development

2020 ◽  
Vol 11 ◽  
Author(s):  
Maider Varela-Guruceaga ◽  
Elise Belaidi ◽  
Lucie Lebeau ◽  
Ella Aka ◽  
Ramaroson Andriantsitohaina ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Intermittent Hypoxia ◽  
Molecular Mechanisms ◽  
Chronic Intermittent Hypoxia ◽  
Resistance Development ◽  
Systemic Insulin Resistance ◽  
Obstructive Sleep ◽  
Protein Expressions ◽  
Resistance State

Repetitive complete or incomplete pharyngeal collapses are leading to chronic intermittent hypoxia (CIH), a hallmark feature of obstructive sleep apnea (OSA) syndrome responsible for many metabolic disorders. In humans, an association between OSA and insulin resistance has been found independently of the degree of obesity. Based on our previous work showing that hypoxia applied to adipocytes led to cellular insulin resistance associated with caveolae flattening, we have investigated the effects of CIH on caveolae structuration in adipose tissue. Original exploratory experiences demonstrate that 6 weeks-exposure of lean mice to CIH is characterized by systemic insulin resistance and translates into adipocyte insulin signaling alterations. Chronic intermittent hypoxia also induces caveolae disassembly in white adipose tissue (WAT) illustrated by reduced plasma membrane caveolae density and enlarged caveolae width, concomitantly to WAT insulin resistance state. We show that CIH downregulates caveolar gene and protein expressions, including cavin-1, cavin-2, and EHD2, underlying molecular mechanisms responsible for such caveolae flattening. Altogether, we provide evidences for adipose tissue caveolae disassembly following CIH exposure, likely linked to cavin protein downregulation. This event may constitute the molecular basis of insulin resistance development in OSA patients.

Adipose tissue hypoxia and insulin resistance

2016 ◽  
Vol 64 (4) ◽  
pp. 830-832 ◽  
Author(s):  
Neda Rasouli
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Tissue Hypoxia ◽  
Sequence Of Events ◽  
Adipose Tissue Dysfunction ◽  
Underlying Mechanisms ◽  
Key Events

Despite the well-established association of obesity with insulin resistance and inflammation, the underlying mechanisms and sequence of events leading to inflammation and insulin resistance remain unknown. Adipose tissue hypoxia has been proposed as one of the possible key events during the process of fat expansion that leads to adipose tissue dysfunction. The focus of this paper is reviewing the evidence on adipose tissue hypoxia in obesity and its relation to insulin resistance.

scholarly journals Intermittent Hypoxia Increases the Severity of Bleomycin-Induced Lung Injury in Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Thomas Gille ◽  
Morgane Didier ◽  
Cécile Rotenberg ◽  
Eva Delbrel ◽  
Dominique Marchant ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pulmonary Fibrosis ◽  
Pulmonary Edema ◽  
Cell Apoptosis ◽  
Lung Fibrosis ◽  
Intermittent Hypoxia ◽  
Chronic Intermittent Hypoxia ◽  
Obstructive Sleep ◽  
The Impact ◽  
Lung Oxidative Stress

Background. Severe obstructive sleep apnea (OSA) with chronic intermittent hypoxia (IH) is common in idiopathic pulmonary fibrosis (IPF). Here, we evaluated the impact of IH on bleomycin- (BLM-) induced pulmonary fibrosis in mice. Methods. C57BL/6J mice received intratracheal BLM or saline and were exposed to IH (40 cycles/hour; FiO2 nadir: 6%; 8 hours/day) or intermittent air (IA). In the four experimental groups, we evaluated (i) survival; (ii) alveolar inflammation, pulmonary edema, lung oxidative stress, and antioxidant enzymes; (iii) lung cell apoptosis; and (iv) pulmonary fibrosis. Results. Survival at day 21 was lower in the BLM-IH group (p<0.05). Pulmonary fibrosis was more severe at day 21 in BLM-IH mice, as assessed by lung collagen content (p=0.02) and histology. At day 4, BLM-IH mice developed a more severe neutrophilic alveolitis, (p<0.001). Lung oxidative stress was observed, and superoxide dismutase and glutathione peroxidase expression was decreased in BLM-IH mice (p<0.05 versus BLM-IA group). At day 8, pulmonary edema was observed and lung cell apoptosis was increased in the BLM-IH group. Conclusion. These results show that exposure to chronic IH increases mortality, lung inflammation, and lung fibrosis in BLM-treated mice. This study raises the question of the worsening impact of severe OSA in IPF patients.

scholarly journals Cardiac Response to Chronic Intermittent Hypoxia with a Transition from Adaptation to Maladaptation:The Role of Hydrogen Peroxide

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Xia Yin ◽  
Yang Zheng ◽  
Quan Liu ◽  
Jun Cai ◽  
Lu Cai
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Intermittent Hypoxia ◽  
Cardiac Response ◽  
Chronic Intermittent Hypoxia ◽  
Critical Element ◽  
Respiratory Disorder ◽  
Obstructive Sleep ◽  
Antioxidative Therapy

Obstructive sleep apnea (OSA) is a highly prevalent respiratory disorder of sleep, and associated with chronic intermittent hypoxia (CIH). Experimental evidence indicates that CIH is a unique physiological state with potentially “adaptive” and “maladaptive” consequences for cardio-respiratory homeostasis. CIH is also a critical element accounting for most of cardiovascular complications of OSA. Cardiac response to CIH is time-dependent, showing a transition from cardiac compensative (such as hypertrophy) to decompensating changes (such as failure). CIH-provoked mild and transient oxidative stress can induce adaptation, but severe and persistent oxidative stress may provoke maladaptation. Hydrogen peroxide as one of major reactive oxygen species plays an important role in the transition of adaptive to maladaptive response to OSA-associated CIH. This may account for the fact that although oxidative stress has been recognized as a driver of cardiac disease progression, clinical interventions with antioxidants have had little or no impact on heart disease and progression. Here we focus on the role of hydrogen peroxide in CIH and OSA, trying to outline the potential of antioxidative therapy in preventing CIH-induced cardiac damage.

scholarly journals Nitration of MnSOD in the Carotid Body and Adrenal Gland Induced by Chronic Intermittent Hypoxia

2018 ◽  
Vol 66 (10) ◽  
pp. 753-765
Author(s):  
Esteban A. Moya ◽  
Paulina Arias ◽  
Rodrigo Iturriaga
Keyword(s):  
Oxidative Stress ◽  
Adrenal Gland ◽  
Enzymatic Activity ◽  
Adrenal Medulla ◽  
Carotid Body ◽  
Intermittent Hypoxia ◽  
Chronic Intermittent Hypoxia ◽  
Sprague Dawley ◽  
Obstructive Sleep ◽  
Key Enzyme

Chronic intermittent hypoxia (CIH), main feature of obstructive sleep apnea, produces nitro-oxidative stress, which contributes to potentiate carotid body (CB) chemosensory discharges and sympathetic-adrenal-axis activity, leading to hypertension. The MnSOD enzymatic activity, a key enzyme on oxidative stress control, is reduced by superoxide-induced nitration. However, the effects of CIH-induced nitration on MnSOD enzymatic activity in the CB and adrenal gland are not known. We studied the effects of CIH on MnSOD protein and immunoreactive (MnSOD-ir) levels in the CB, adrenal gland and superior cervical ganglion (SCG), and on 3-nitrotyrosine (3-NT-ir), CuZnSOD (CuZnSOD-ir), MnSOD nitration, and its enzymatic activity in the CB and adrenal gland from male Sprague-Dawley rats exposed to CIH for 7 days. CIH increased 3-NT-ir in CB and adrenal gland, whereas MnSOD-ir increased in the CB and in adrenal cortex, but not in the whole adrenal medulla or SCG. CIH nitrated MnSOD in the CB and adrenal medulla, but its activity decreased in the adrenal gland. CuZnSOD-ir remained unchanged in both tissues. All changes observed were prevented by ascorbic acid treatment. Present results show that CIH for 7 days produced MnSOD nitration, but failed to reduce its activity in the CB, because of the increased protein level.

scholarly journals Curcumin prevents chronic intermittent hypoxia-induced myocardial injury

2020 ◽  
Vol 11 ◽  
pp. 204062232092210 ◽  
Author(s):  
Sophie Moulin ◽  
Claire Arnaud ◽  
Sophie Bouyon ◽  
Jean-Louis Pépin ◽  
Diane Godin-Ribuot ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Infarct Size ◽  
Er Stress ◽  
Intermittent Hypoxia ◽  
Myocardial Injury ◽  
Ischemia Reperfusion ◽  
Sleep Apnoea ◽  
Cardiac Response ◽  
Chronic Intermittent Hypoxia ◽  
Obstructive Sleep

Background: Chronic intermittent hypoxia (IH), the hallmark feature of obstructive sleep apnoea syndrome, contributes to infarct size enhancement after myocardial ischemia–reperfusion (I/R). Curcumin (Curc), the natural pigment of Curcuma longa, has been demonstrated to be beneficial in the context of myocardial injury. In this study, we assessed the effects of Curc on the maladaptive cardiac response to IH, and particularly on IH-induced hypoxia inducible factor-1 (HIF-1) expression, oxidative stress, inflammation, endoplasmic reticulum (ER) stress and apoptosis. Methods: Swiss/SV129 mice were exposed to normoxia or IH (21–5% FiO2, 60 s cycles, 8 h per day, for 21 days) and treated orally with Curc (100 mg kg−1 day−1, oral gavage) or its vehicle. Mice were then either euthanised for heart sampling in order to perform biochemical and histological analysis, or subjected to an in vivo ischemia-reperfusion protocol in order to measure infarct size. Results: IH increased nuclear HIF-1α expression and superoxide anion (O2.–) production as well as nuclear factor kappa B (NF-kB) p65, glucose-regulated protein (Grp78) and C/EBP homologous protein (CHOP) expression. IH also induced apoptosis and increased infarct size after I/R . The IH-induced HIF-1 activation, oxidative stress, inflammation, ER stress and apoptosis were abolished by chronic Curc treatment. Curc also significantly decreased infarct size only in mice exposed to IH. Conclusion: Curc prevents IH-induced myocardial cell death signalling. Curc might be used as a combined therapy with continuous positive airway pressure in sleep apnoea patients with high cardiovascular risk.

scholarly journals Intermittent hypoxia in obstructive sleep apnoea mediates insulin resistance through adipose tissue inflammation

2017 ◽  
Vol 49 (4) ◽  
pp. 1601731 ◽  
Author(s):  
Aoife M. Murphy ◽  
Amandine Thomas ◽  
Sophie J. Crinion ◽  
Brian D. Kent ◽  
Murtaza M. Tambuwala ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Obstructive Sleep Apnoea ◽  
Intermittent Hypoxia ◽  
Insulin Signalling ◽  
Sleep Apnoea ◽  
M1 Macrophage ◽  
Insulin Signalling Pathway ◽  
Obstructive Sleep ◽  
Inflammatory Phenotype

Obstructive sleep apnoea (OSA) is increasingly associated with insulin resistance. The underlying pathophysiology remains unclear but intermittent hypoxia (IH)-mediated inflammation and subsequent dysfunction of the adipose tissue has been hypothesised to play a key role.We tested this hypothesis employing a comprehensive translational approach using a murine IH model of lean and diet-induced obese mice, an innovative IH system for cell cultures and a tightly controlled patient cohort.IH led to the development of insulin resistance in mice, corrected for the degree of obesity, and reduced insulin-mediated glucose uptake in 3T3-L1 adipocytes, associated with inhibition of the insulin-signalling pathway and downregulation of insulin-receptor substrate-1 mRNA. Providing mechanistic insight, IH induced a pro-inflammatory phenotype of visceral adipose tissue in mice with pro-inflammatory M1 macrophage polarisation correlating with the severity of insulin resistance. Complimentaryin vitroanalysis demonstrated that IH led to M1 polarisation of THP1-derived macrophages. In subjects without comorbidities (n=186), OSA was independently associated with insulin resistance. Furthermore, we found an independent correlation of OSA severity with the M1 macrophage inflammatory marker sCD163.This study provides evidence that IH induces a pro-inflammatory phenotype of the adipose tissue, which may be a crucial link between OSA and the development of insulin resistance.

scholarly journals Effects of Chronic Intermittent Hypoxia and Chronic Sleep Fragmentation on Gut Microbiome, Serum Metabolome, Liver and Adipose Tissue Morphology

2021 ◽  
Author(s):  
Fan Wang ◽  
Juanjuan Zou ◽  
Huajun Xu ◽  
Weijun Huang ◽  
Xiaoman Zhang ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Lipid Metabolism ◽  
Intermittent Hypoxia ◽  
Synergistic Effects ◽  
Sleep Fragmentation ◽  
Chronic Intermittent Hypoxia ◽  
Intestinal Microbes ◽  
Tissue Morphology ◽  
Obstructive Sleep ◽  
Chronic Sleep

Chronic intermittent hypoxia (CIH) and chronic sleep fragmentation (CSF) are two cardinal pathological features of obstructive sleep apnea (OSA). Dietary obesity is a crucial risk intermediator for OSA and metabolic disorders. Gut microbiota affect hepatic and adipose tissue morphology under conditions of CIH or CSF through downstream metabolites. However, the exact relationship is unclear. Herein, chow and high-fat diet (HFD)-fed mice were subjected to CIH or CSF for 10 weeks each and compared to normoxia (NM) or normal sleep (NS) controls. 16S rRNA amplicon sequencing, untargeted liquid chromatography-tandem mass spectrometry, and histological assessment of liver and adipose tissues were used to investigate the correlations between the microbiome, metabolome, and lipid metabolism under CIH or CSF condition. Our results demonstrated that CIH and CSF regulate the abundance of intestinal microbes (such as Akkermansia mucinphila, Clostridium spp., Lactococcus spp., and Bifidobacterium spp.) and functional metabolites, such as tryptophan, free fatty acids, branched amino acids, and bile acids, which influence adipose tissue and hepatic lipid metabolism, and the level of lipid deposition in tissues and peripheral blood. In conclusion, CIH and CSF adversely affect fecal microbiota composition and function, and host metabolism; these findings provide new insight into the independent and synergistic effects of CIH, CSF, and HFD on lipid disorders.

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