Long-term intermittent hypoxia in mice induces inflammatory pathways implicated in sleep apnea and steatohepatitis in humans
Summary: Obstructive sleep apnea (OSA) induces intermittent hypoxia (IH), an independent risk factor for non-alcoholic fatty liver disease (NAFLD). While the molecular links between IH and NAFLD progression are unclear, immune cell-driven inflammation plays a crucial role in NAFLD pathogenesis. Usin...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-02-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224000580 |
| _version_ | 1797348633861947392 |
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| author | Jonathan Gaucher Emilie Montellier Guillaume Vial Florent Chuffart Maëlle Guellerin Sophie Bouyon Emeline Lemarie Yoshiki Yamaryo Botté Aya Dirani Raoua Ben Messaoud Marie Joyeux Faure Diane Godin Ribuot Charlotte Costentin Renaud Tamisier Cyrille Y. Botté Saadi Khochbin Sophie Rousseaux Jean-Louis Pépin |
| author_facet | Jonathan Gaucher Emilie Montellier Guillaume Vial Florent Chuffart Maëlle Guellerin Sophie Bouyon Emeline Lemarie Yoshiki Yamaryo Botté Aya Dirani Raoua Ben Messaoud Marie Joyeux Faure Diane Godin Ribuot Charlotte Costentin Renaud Tamisier Cyrille Y. Botté Saadi Khochbin Sophie Rousseaux Jean-Louis Pépin |
| author_sort | Jonathan Gaucher |
| collection | DOAJ |
| description | Summary: Obstructive sleep apnea (OSA) induces intermittent hypoxia (IH), an independent risk factor for non-alcoholic fatty liver disease (NAFLD). While the molecular links between IH and NAFLD progression are unclear, immune cell-driven inflammation plays a crucial role in NAFLD pathogenesis. Using lean mice exposed to long-term IH and a cohort of lean OSA patients (n = 71), we conducted comprehensive hepatic transcriptomics, lipidomics, and targeted serum proteomics. Significantly, we demonstrated that long-term IH alone can induce NASH molecular signatures found in human steatohepatitis transcriptomic data. Biomarkers (PPARs, NRFs, arachidonic acid, IL16, IL20, IFNB, TNF-α) associated with early hepatic and systemic inflammation were identified. This molecular link between IH, sleep apnea, and steatohepatitis merits further exploration in clinical trials, advocating for integrating sleep apnea diagnosis in liver disease phenotyping. Our unique signatures offer potential diagnostic and treatment response markers, highlighting therapeutic targets in the comorbidity of NAFLD and OSA. |
| first_indexed | 2024-03-08T12:08:35Z |
| format | Article |
| id | doaj.art-50f1fd3578d44f6282cef4b729923a4e |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-08T12:08:35Z |
| publishDate | 2024-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-50f1fd3578d44f6282cef4b729923a4e2024-01-23T04:15:58ZengElsevieriScience2589-00422024-02-01272108837Long-term intermittent hypoxia in mice induces inflammatory pathways implicated in sleep apnea and steatohepatitis in humansJonathan Gaucher0Emilie Montellier1Guillaume Vial2Florent Chuffart3Maëlle Guellerin4Sophie Bouyon5Emeline Lemarie6Yoshiki Yamaryo Botté7Aya Dirani8Raoua Ben Messaoud9Marie Joyeux Faure10Diane Godin Ribuot11Charlotte Costentin12Renaud Tamisier13Cyrille Y. Botté14Saadi Khochbin15Sophie Rousseaux16Jean-Louis Pépin17Hypoxia and Physio-Pathology Laboratory (HP2) INSERM U1300, University Grenoble Alpes, INSERM U1300, and Grenoble Alpes University Hospital, Grenoble, France; Corresponding authorCancers and Biomarkers Team, Institute for Advanced Biosciences, University, INSERM U1209, CNRS UMR5309, University Grenoble Alpes, Grenoble, FranceHypoxia and Physio-Pathology Laboratory (HP2) INSERM U1300, University Grenoble Alpes, INSERM U1300, and Grenoble Alpes University Hospital, Grenoble, FranceEpigenetics Regulation Team, Institute for Advanced Biosciences INSERM U1209, CNRS UMR5309, University Grenoble Alpes, Grenoble, FranceHypoxia and Physio-Pathology Laboratory (HP2) INSERM U1300, University Grenoble Alpes, INSERM U1300, and Grenoble Alpes University Hospital, Grenoble, FranceHypoxia and Physio-Pathology Laboratory (HP2) INSERM U1300, University Grenoble Alpes, INSERM U1300, and Grenoble Alpes University Hospital, Grenoble, FranceHypoxia and Physio-Pathology Laboratory (HP2) INSERM U1300, University Grenoble Alpes, INSERM U1300, and Grenoble Alpes University Hospital, Grenoble, FranceApicolipid Team, Institute for Advanced Biosciences INSERM U1209, CNRS UMR5309, University Grenoble Alpes, Grenoble, FranceHypoxia and Physio-Pathology Laboratory (HP2) INSERM U1300, University Grenoble Alpes, INSERM U1300, and Grenoble Alpes University Hospital, Grenoble, FranceHypoxia and Physio-Pathology Laboratory (HP2) INSERM U1300, University Grenoble Alpes, INSERM U1300, and Grenoble Alpes University Hospital, Grenoble, FranceHypoxia and Physio-Pathology Laboratory (HP2) INSERM U1300, University Grenoble Alpes, INSERM U1300, and Grenoble Alpes University Hospital, Grenoble, FranceHypoxia and Physio-Pathology Laboratory (HP2) INSERM U1300, University Grenoble Alpes, INSERM U1300, and Grenoble Alpes University Hospital, Grenoble, FranceHypoxia and Physio-Pathology Laboratory (HP2) INSERM U1300, University Grenoble Alpes, INSERM U1300, and Grenoble Alpes University Hospital, Grenoble, FranceHypoxia and Physio-Pathology Laboratory (HP2) INSERM U1300, University Grenoble Alpes, INSERM U1300, and Grenoble Alpes University Hospital, Grenoble, FranceApicolipid Team, Institute for Advanced Biosciences INSERM U1209, CNRS UMR5309, University Grenoble Alpes, Grenoble, FranceEpigenetics Regulation Team, Institute for Advanced Biosciences INSERM U1209, CNRS UMR5309, University Grenoble Alpes, Grenoble, FranceEpigenetics Regulation Team, Institute for Advanced Biosciences INSERM U1209, CNRS UMR5309, University Grenoble Alpes, Grenoble, FranceHypoxia and Physio-Pathology Laboratory (HP2) INSERM U1300, University Grenoble Alpes, INSERM U1300, and Grenoble Alpes University Hospital, Grenoble, France; Corresponding authorSummary: Obstructive sleep apnea (OSA) induces intermittent hypoxia (IH), an independent risk factor for non-alcoholic fatty liver disease (NAFLD). While the molecular links between IH and NAFLD progression are unclear, immune cell-driven inflammation plays a crucial role in NAFLD pathogenesis. Using lean mice exposed to long-term IH and a cohort of lean OSA patients (n = 71), we conducted comprehensive hepatic transcriptomics, lipidomics, and targeted serum proteomics. Significantly, we demonstrated that long-term IH alone can induce NASH molecular signatures found in human steatohepatitis transcriptomic data. Biomarkers (PPARs, NRFs, arachidonic acid, IL16, IL20, IFNB, TNF-α) associated with early hepatic and systemic inflammation were identified. This molecular link between IH, sleep apnea, and steatohepatitis merits further exploration in clinical trials, advocating for integrating sleep apnea diagnosis in liver disease phenotyping. Our unique signatures offer potential diagnostic and treatment response markers, highlighting therapeutic targets in the comorbidity of NAFLD and OSA.http://www.sciencedirect.com/science/article/pii/S2589004224000580Natural sciencesBiological sciencesPhysiologyAnimal physiologyHuman Physiology |
| spellingShingle | Jonathan Gaucher Emilie Montellier Guillaume Vial Florent Chuffart Maëlle Guellerin Sophie Bouyon Emeline Lemarie Yoshiki Yamaryo Botté Aya Dirani Raoua Ben Messaoud Marie Joyeux Faure Diane Godin Ribuot Charlotte Costentin Renaud Tamisier Cyrille Y. Botté Saadi Khochbin Sophie Rousseaux Jean-Louis Pépin Long-term intermittent hypoxia in mice induces inflammatory pathways implicated in sleep apnea and steatohepatitis in humans iScience Natural sciences Biological sciences Physiology Animal physiology Human Physiology |
| title | Long-term intermittent hypoxia in mice induces inflammatory pathways implicated in sleep apnea and steatohepatitis in humans |
| title_full | Long-term intermittent hypoxia in mice induces inflammatory pathways implicated in sleep apnea and steatohepatitis in humans |
| title_fullStr | Long-term intermittent hypoxia in mice induces inflammatory pathways implicated in sleep apnea and steatohepatitis in humans |
| title_full_unstemmed | Long-term intermittent hypoxia in mice induces inflammatory pathways implicated in sleep apnea and steatohepatitis in humans |
| title_short | Long-term intermittent hypoxia in mice induces inflammatory pathways implicated in sleep apnea and steatohepatitis in humans |
| title_sort | long term intermittent hypoxia in mice induces inflammatory pathways implicated in sleep apnea and steatohepatitis in humans |
| topic | Natural sciences Biological sciences Physiology Animal physiology Human Physiology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224000580 |
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