학술논문
Long-term intermittent hypoxia in mice induces inflammatory pathways implicated in sleep apnea and steatohepatitis in humans
Document Type
article
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
Source
iScience, Vol 27, Iss 2, Pp 108837- (2024)
Subject
Language
English
ISSN
2589-0042
Abstract
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.