Photobiomodulation with 650 nm Wavelength Mediates Endoplasmic Reticulum-Mitochondria Contact and Ameliorates Lipotoxicity in NAFLD via Mfn2/PERK/CHOP Signaling

Photobiomodulation with 650 nm Wavelength Mediates Endoplasmic Reticulum-Mitochondria Contact and Ameliorates Lipotoxicity in NAFLD via Mfn2/PERK/CHOP Signaling | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Photobiomodulation with 650 nm Wavelength Mediates Endoplasmic Reticulum-Mitochondria Contact and Ameliorates Lipotoxicity in NAFLD via Mfn2/PERK/CHOP Signaling Min Yao, Zhixuan Jiang, Shan Wu, Shengzhe Zhou, Hongjie Zheng, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5625995/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract The disruption of mitochondria associated membranes (MAMs) is involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) by modulating endoplasmic reticulum stress (ERS) and mitochondrial malfunction induced by lipotoxicity. Photobiomodulation (PBM), as a non-invasive physical therapy, has been demonstrated to improve cellular metabolim in various diseases. Here we found that PBM with 650 nm ameliorated lipid accumulation and liver injury in high-fat-diet-fed mice. Moreover, MAMs integrity was restored in liver tissues of NAFLD after PBM. Correspondingly, PBM enhanced mitochondria-ER colocalization and improved mitochondrial homeostasis in fatty-acid-treated HepG2 cells. Mechanically, Mfn2 expression was selectively elevated by PBM, accompanied by downregulation of PERK, p-PERK, and CHOP. The beneficial effects of PBM were diminished by Mfn2 knockdown, while PERK activity regulated mitochondrial function without altering MAMs formation. Thus, PBM relieves lipotoxicity in NAFLD by enhancing MAMs integrity via the Mfn2/PERK/CHOP pathway. Our findings may provide evidence for noninvasive physical light therapeutics for lifestyle-related metabolic diseases. Biological sciences/Cell biology/Cell signalling/Stress signalling Health sciences/Gastroenterology/Hepatology/Liver diseases/Non-alcoholic fatty liver disease NAFLD photobiomodulation MAMs mitochondria Mfn2 PERK Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplementaryMaterials.docx Supplementary Information Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5625995","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":399915506,"identity":"21614c9c-70be-4128-b71d-8bf04a12375e","order_by":0,"name":"Min 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