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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 o...

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Autores principales: Varela-Guruceaga, Maider, Belaidi, Elise, Lebeau, Lucie, Aka, Ella, Andriantsitohaina, Ramaroson, Giorgetti-Peraldi, Sophie, Arnaud, Claire, Le Lay, Soazig
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726350/
https://www.ncbi.nlm.nih.gov/pubmed/33324235
http://dx.doi.org/10.3389/fphys.2020.565486
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author Varela-Guruceaga, Maider
Belaidi, Elise
Lebeau, Lucie
Aka, Ella
Andriantsitohaina, Ramaroson
Giorgetti-Peraldi, Sophie
Arnaud, Claire
Le Lay, Soazig
author_facet Varela-Guruceaga, Maider
Belaidi, Elise
Lebeau, Lucie
Aka, Ella
Andriantsitohaina, Ramaroson
Giorgetti-Peraldi, Sophie
Arnaud, Claire
Le Lay, Soazig
author_sort Varela-Guruceaga, Maider
collection PubMed
description 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.
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spelling pubmed-77263502020-12-14 Intermittent Hypoxia Mediates Caveolae Disassembly That Parallels Insulin Resistance Development Varela-Guruceaga, Maider Belaidi, Elise Lebeau, Lucie Aka, Ella Andriantsitohaina, Ramaroson Giorgetti-Peraldi, Sophie Arnaud, Claire Le Lay, Soazig Front Physiol Physiology 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. Frontiers Media S.A. 2020-11-26 /pmc/articles/PMC7726350/ /pubmed/33324235 http://dx.doi.org/10.3389/fphys.2020.565486 Text en Copyright © 2020 Varela-Guruceaga, Belaidi, Lebeau, Aka, Andriantsitohaina, Giorgetti-Peraldi, Arnaud and Le Lay. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Varela-Guruceaga, Maider
Belaidi, Elise
Lebeau, Lucie
Aka, Ella
Andriantsitohaina, Ramaroson
Giorgetti-Peraldi, Sophie
Arnaud, Claire
Le Lay, Soazig
Intermittent Hypoxia Mediates Caveolae Disassembly That Parallels Insulin Resistance Development
title Intermittent Hypoxia Mediates Caveolae Disassembly That Parallels Insulin Resistance Development
title_full Intermittent Hypoxia Mediates Caveolae Disassembly That Parallels Insulin Resistance Development
title_fullStr Intermittent Hypoxia Mediates Caveolae Disassembly That Parallels Insulin Resistance Development
title_full_unstemmed Intermittent Hypoxia Mediates Caveolae Disassembly That Parallels Insulin Resistance Development
title_short Intermittent Hypoxia Mediates Caveolae Disassembly That Parallels Insulin Resistance Development
title_sort intermittent hypoxia mediates caveolae disassembly that parallels insulin resistance development
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726350/
https://www.ncbi.nlm.nih.gov/pubmed/33324235
http://dx.doi.org/10.3389/fphys.2020.565486
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