Intermittent hypoxia increases lipid insulin resistance in healthy humans: A randomized crossover trial.

Sympathetic overactivity caused by chronic intermittent hypoxia is a hallmark of obstructive sleep apnea. A high sympathetic tone elicits increases in plasma free fatty acid and insulin. Our objective was to assess the impact of 14 nights of chronic intermittent hypoxia exposure on sympathetic activity, glucose control, lipid profile and subcutaneous fat tissue remodelling in non-obese healthy humans.

Interplay between hypoxia inducible Factor-1 and mitochondria in cardiac diseases.

Ischemic heart diseases and cardiomyopathies are characterized by hypoxia, energy starvation and mitochondrial dysfunction. HIF-1 acts as a cellular oxygen sensor, tuning the balance of metabolic and oxidative stress pathways to provide ATP and sustain cell survival. Acting on mitochondria, HIF-1 regulates different processes such as energy substrate utilization, oxidative phosphorylation and mitochondrial dynamics.

Loss of testosterone induces postprandial insulin resistance and increases the expression of the hepatic antioxidant flavin-containing monooxygenases in mice exposed to intermittent hypoxia.

Aim: We tested the hypothesis that low testosterone alters the effects of intermittent hypoxia (IH) on glucose homeostasis, hepatic oxidative stress, and transcriptomic profile in male mice.

Methods: We used sham-operated or orchiectomized (ORX) mice exposed to normoxia (Nx) or IH for 2 weeks. We performed fasting insulin and glucose tolerance tests and assessed fasting and postprandial insulin resistance with the HOMA-IR.

Chronic intermittent hypoxia due to obstructive sleep apnea slightly alters nutritional status: a pre-clinical study.

Obstructive sleep apnea syndrome (OSAS) is associated with chronic intermittent hypoxia (cIH) that causes disturbances in glucose and lipid metabolism. Animals exposed to cIH show lower body weight and food intake, but the protein-energy metabolism has never been investigated. Here, to address the gap, we studied the impact of cIH on nutritional status in rats.

L-Citrulline Supplementation Reduces Blood Pressure and Myocardial Infarct Size under Chronic Intermittent Hypoxia, a Major Feature of Sleep Apnea Syndrome.

Intermittent hypoxia (IH) is a landmark of obstructive sleep apnea (OSA) at the core of the cardiovascular consequences of OSA. IH triggers oxidative stress, a major underlying mechanism for elevated blood pressure (BP) and increased infarct size. L-citrulline is an amino acid that has been demonstrated to be protective of the cardiovascular system and exert pleiotropic effects.

Intermittent Hypoxia-Induced Cardiomyocyte Death Is Mediated by HIF-1 Dependent MAM Disruption.

Rationale: Intermittent hypoxia (IH) is one of the main features of sleep-disordered breathing (SDB). Recent findings indicate that hypoxia inducible factor-1 (HIF-1) promotes cardiomyocytes apoptosis during chronic IH, but the mechanisms involved remain to be elucidated. Here, we hypothesize that IH-induced ER stress is associated with mitochondria-associated ER membrane (MAM) alteration and mitochondrial dysfunction, through HIF-1 activation.

Cardiac consequences of intermittent hypoxia: a matter of dose? A systematic review and meta-analysis in rodents.

Aim: Intermittent hypoxia (IH) is considered to be a major contributor to obstructive sleep apnoea-related cardiovascular consequences. The present meta-analysis aimed to assess the effects of IH on cardiac remodelling, function and infarct size after myocardial ischaemia across different rodent species and IH severities.

Methods And Results: Relevant articles from PubMed, Embase and Web of Science were screened.

Intermittent Hypoxia Rewires the Liver Transcriptome and Fires up Fatty Acids Usage for Mitochondrial Respiration.

Sleep Apnea Syndrome (SAS) is one of the most common chronic diseases, affecting nearly one billion people worldwide. The repetitive occurrence of abnormal respiratory events generates cyclical desaturation-reoxygenation sequences known as intermittent hypoxia (IH). Among SAS metabolic sequelae, it has been established by experimental and clinical studies that SAS is an independent risk factor for the development and progression of non-alcoholic fatty liver disease (NAFLD).

Intermittent hypoxia-related alterations in vascular structure and function: a systematic review and meta-analysis of rodent data.

Background: Obstructive sleep apnoea and the related intermittent hypoxia (IH) are widely recognised as risk factors for incident cardiovascular diseases. Numerous studies support the deleterious vascular impact of IH in rodents but an overall interpretation is challenging owing to heterogeneity in rodent species investigated and the severity and duration of IH exposure. To clarify this major issue, we conducted a systematic review and meta-analysis to quantify the impact of IH on systemic artery structure and function depending on the different IH exposure designs.

Impact of obstructive sleep apnoea and intermittent hypoxia on blood rheology: a translational study.

Background: Haemorheological alterations are reported in obstructive sleep apnoea (OSA) and reversed with continuous positive airway pressure (CPAP), observations potentially explained by intermittent hypoxia (IH)-induced oxidative stress. Our objective was to investigate whether IH causes haemorheological alterations oxidative stress.

Methods: Wistar rats were exposed to normoxia (n=7) or IH (n=8) for 14 days.

Short-term intermittent hypoxia induces simultaneous systemic insulin resistance and higher cardiac contractility in lean mice.

Background: Intermittent hypoxia (IH) is the major feature of obstructive sleep apnea syndrome, well-known to induce cardiometabolic complications. We previously demonstrated that IH induces hyperinsulinemia and associated altered insulin signaling in adipose tissue, liver, and skeletal muscle, but impact of IH on cardiac insulin signaling and functional/structural consequences remains unknown. Therefore, the aims of this study were to investigate in both lean and obese mice the effects of chronic IH on the following: (1) cardiac insulin signaling and (2) cardiac remodeling and function.

Intermittent Hypoxia Mediates Caveolae Disassembly That Parallels Insulin Resistance Development.

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.

Intermittent Hypoxia Triggers Early Cardiac Remodeling and Contractile Dysfunction in the Time-Course of Ischemic Cardiomyopathy in Rats.

BACKGROUND Sleep-disordered breathing is associated with a poor prognosis (mortality) in patients with ischemic cardiomyopathy. The understanding of mechanisms linking intermittent hypoxia (IH), the key feature of sleep-disordered breathing, to ischemic cardiomyopathy progression is crucial for identifying specific actionable therapeutic targets. The aims of the present study were (1) to evaluate the impact of IH on the time course evolution of cardiac remodeling and contractile dysfunction in a rat model of ischemic cardiomyopathy; and (2) to determine the impact of IH on sympathetic activity, hypoxia inducible factor-1 activation, and endoplasmic reticulum stress in the time course of ischemic cardiomyopathy progression.

Curcumin prevents chronic intermittent hypoxia-induced myocardial injury.

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 , 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.

Cardiovascular and metabolic responses to passive hypoxic conditioning in overweight and mildly obese individuals.

Although severe intermittent hypoxia (IH) is well known to induce deleterious cardiometabolic consequences, moderate IH may induce positive effects in obese individuals. The present study aimed to evaluate the effect of two hypoxic conditioning programs on cardiovascular and metabolic health status of overweight or obese individuals. In this randomized single-blind controlled study, 35 subjects (54 ± 9.

Activin-A limits Th17 pathogenicity and autoimmune neuroinflammation via CD39 and CD73 ectonucleotidases and Hif1-α-dependent pathways.

In multiple sclerosis (MS), Th17 cells are critical drivers of autoimmune central nervous system (CNS) inflammation and demyelination. Th17 cells exhibit functional heterogeneity fostering both pathogenic and nonpathogenic, tissue-protective functions. Still, the factors that control Th17 pathogenicity remain incompletely defined.

Cooperation Between Hypoxia-Inducible Factor 1α and Activating Transcription Factor 4 in Sleep Apnea-Mediated Myocardial Injury.

Chronic intermittent hypoxia (CIH) occurring during sleep apnea amplifies infarct size owing to ischemia-reperfusion. CIH activates hypoxia-inducible factor 1 (HIF-1) and activating transcription factor 4 (ATF4). However, whether HIF-1 and ATF4 interact to promote cardiomyocyte death remains unexplored.

Obstructive sleep apnoea and cardiovascular consequences: Pathophysiological mechanisms.

Obstructive sleep apnoea syndrome is a growing health concern, affecting nearly one billion people worldwide; it is an independent cardiovascular risk factor, associated with incident obesity, insulin resistance, hypertension, arrhythmias, stroke, coronary artery disease and heart failure. Obstructive sleep apnoea-related cardiovascular and metabolic co-morbidities are a major concern for prognosis and the complexity of obstructive sleep apnoea integrated care. Continuous positive airway pressure, the first-line therapy for the treatment of obstructive sleep apnoea, is highly effective at improving symptoms and quality of life, but has limited effect on co-morbidities.

Hypoxic Exercise Training to Improve Exercise Capacity in Obese Individuals.

Introduction: 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.

Lebetin 2, a Snake Venom-Derived B-Type Natriuretic Peptide, Provides Immediate and Prolonged Protection against Myocardial Ischemia-Reperfusion Injury via Modulation of Post-Ischemic Inflammatory Response.

Myocardial infarction (MI) followed by left ventricular (LV) remodeling is the most frequent cause of heart failure. Lebetin 2 (L2), a snake venom-derived natriuretic peptide, exerts cardioprotection during acute myocardial ischemia-reperfusion (IR) ex vivo. However, its effects on delayed consequences of IR injury, including post-MI inflammation and fibrosis have not been defined.

Effects of acute nitric oxide precursor intake on peripheral and central fatigue during knee extensions in healthy men.

New Findings: What is the central question of this study? What is the effect of acute NO precursor intake on vascular function, muscle and cerebral oxygenation and peripheral and central neuromuscular fatigue during knee-extension exercise? What is the main finding and its importance? Acute NO precursor ingestion increases the plasma concentrations of NO precursors (nitrate, arginine and citrulline) and enhances post-ischaemic vasodilatation, but has no significant effect on muscle and cerebral oxygenation, peripheral and central mechanisms of neuromuscular fatigue and, consequently, does not improve exercise performance.

Abstract: Nitric oxide (NO) plays an important role in matching blood flow to oxygen demand in the brain and contracting muscles during exercise. Previous studies have shown that increasing NO bioavailability can improve muscle function.

Cysteinyl-leukotriene pathway as a new therapeutic target for the treatment of atherosclerosis related to obstructive sleep apnea syndrome.

Aims: Obstructive sleep apnea (OSA) characterized by nocturnal intermittent hypoxia (IH) is associated with atherosclerosis and cysteinyl-leukotrienes (CysLT) pathway activation. We aimed to identify the determinants of CysLT pathway activation and the role of CysLT in OSA-related atherosclerosis.

Methods And Results: Determinants of the urinary excretion of LTE (U-LTE) including history of cardiovascular events, polysomnographic and biological parameters were studied in a cohort of 170 OSA patients and 29 controls, and in a subgroup of OSA patients free of cardiovascular event (n = 136).