High-Fat Diet-Induced Lipid Metabolic Dysregulation Activates Inflammatory Signaling Pathways Regulating Ocular Growth

High-Fat Diet-Induced Lipid Metabolic Dysregulation Activates Inflammatory Signaling Pathways Regulating Ocular Growth | 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 Research Article High-Fat Diet-Induced Lipid Metabolic Dysregulation Activates Inflammatory Signaling Pathways Regulating Ocular Growth Xiaoran Zhang, Yamin Chen, Kailei Wang, Ning Zhang, Zichen Luan, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8554000/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 05 Mar, 2026 Read the published version in Journal of Translational Medicine → Version 1 posted 4 You are reading this latest preprint version Abstract Background Myopia has become a major global public health concern, with increasing evidence linking diet and inflammation to its development. Objective To investigate the effects of a high-fat diet (HFD) on refractive development and myopia progression in guinea pigs. Methods Thirty-two 3-week-old pigmented guinea pigs were randomly assigned to four groups: Control, HFD, lens-induced myopia (LIM), and lens-induced myopia with high-fat diet (LIM + HFD) group. The HFD group was fed a high fat diet for 4 weeks, while myopia was induced in the right eye of LIM and LIM + HFD groups using a -10D lens. Ocular parameters, including refractive error (RE), axial length (AL), retinal thickness (RT), choroidal thickness (ChT), and choroidal blood perfusion (ChBP), were measured at baseline, 2 and 4 weeks. Serum lipids (TC, TG, HDL, LDL) were assessed using an automated biochemical analyzer and serum and retinal levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and nuclear factor kappa-B (NF-kB) were evaluated by ELISA and qPCR at baseline and 4 weeks. Results After 4 weeks, HFD and LIM + HFD groups developed dyslipidemia with elevated TC, TG, and LDL (P < 0.01). Compared with controls, the HFD group showed decreased RE, increased AL, and reduced RT, ChT, and ChBP (P 0.05). However, in fellow eyes, LIM + HFD induced HFD-like structural and functional changes, significantly different from LIM alone (P < 0.001). ELISA and qPCR revealed elevated IL-1β, IL-6, and NF-kB in HFD and LIM groups, with the highest levels in LIM + HFD. Conclusions A 4-week HFD increased susceptibility to myopia during normal refractive development but did not worsen lens-induced myopia. HFD was associated with enhanced systemic and retinal inflammation, suggesting a potential link between diet-induced inflammation and increased myopia susceptibility. High fat diet Inflammation Myopia Guinea pigs OCT Full Text Cite Share Download PDF Status: Published Journal Publication published 05 Mar, 2026 Read the published version in Journal of Translational Medicine → Version 1 posted Reviewers agreed at journal 21 Jan, 2026 Reviewers invited by journal 21 Jan, 2026 Editor assigned by journal 10 Jan, 2026 First submitted to journal 08 Jan, 2026 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-8554000","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":578411572,"identity":"cdc6a9ee-6307-49b5-8be9-4f82d4b52013","order_by":0,"name":"Xiaoran 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Growth","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-translational-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jtrm","sideBox":"Learn more about [Journal of Translational Medicine](http://translational-medicine.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/jtrm/default.aspx","title":"Journal of Translational Medicine","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"High fat diet, Inflammation, Myopia, Guinea pigs, OCT","lastPublishedDoi":"10.21203/rs.3.rs-8554000/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8554000/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eMyopia has become a major global public health concern, with increasing evidence linking diet and inflammation to its development.\u003c/p\u003e\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eTo investigate the effects of a high-fat diet (HFD) on refractive development and myopia progression in guinea pigs.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThirty-two 3-week-old pigmented guinea pigs were randomly assigned to four groups: Control, HFD, lens-induced myopia (LIM), and lens-induced myopia with high-fat diet (LIM\u0026thinsp;+\u0026thinsp;HFD) group. The HFD group was fed a high fat diet for 4 weeks, while myopia was induced in the right eye of LIM and LIM\u0026thinsp;+\u0026thinsp;HFD groups using a -10D lens. Ocular parameters, including refractive error (RE), axial length (AL), retinal thickness (RT), choroidal thickness (ChT), and choroidal blood perfusion (ChBP), were measured at baseline, 2 and 4 weeks. Serum lipids (TC, TG, HDL, LDL) were assessed using an automated biochemical analyzer and serum and retinal levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and nuclear factor kappa-B (NF-kB) were evaluated by ELISA and qPCR at baseline and 4 weeks.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAfter 4 weeks, HFD and LIM\u0026thinsp;+\u0026thinsp;HFD groups developed dyslipidemia with elevated TC, TG, and LDL (P\u0026thinsp;\u0026lt;\u0026thinsp;0.01). Compared with controls, the HFD group showed decreased RE, increased AL, and reduced RT, ChT, and ChBP (P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), indicating greater susceptibility to myopia. In lens-wearing eyes, LIM\u0026thinsp;+\u0026thinsp;HFD did not exacerbate myopic progression compared with LIM (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). However, in fellow eyes, LIM\u0026thinsp;+\u0026thinsp;HFD induced HFD-like structural and functional changes, significantly different from LIM alone (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). ELISA and qPCR revealed elevated IL-1β, IL-6, and NF-kB in HFD and LIM groups, with the highest levels in LIM\u0026thinsp;+\u0026thinsp;HFD.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eA 4-week HFD increased susceptibility to myopia during normal refractive development but did not worsen lens-induced myopia. HFD was associated with enhanced systemic and retinal inflammation, suggesting a potential link between diet-induced inflammation and increased myopia susceptibility.\u003c/p\u003e","manuscriptTitle":"High-Fat Diet-Induced Lipid Metabolic Dysregulation Activates Inflammatory Signaling Pathways Regulating Ocular Growth","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-23 21:29:04","doi":"10.21203/rs.3.rs-8554000/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2026-01-22T02:03:05+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-22T00:53:19+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-10T05:11:29+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Translational Medicine","date":"2026-01-08T12:20:47+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-translational-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jtrm","sideBox":"Learn more about [Journal of Translational Medicine](http://translational-medicine.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/jtrm/default.aspx","title":"Journal of Translational Medicine","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d65b5a7d-98ee-46ad-98a2-369d7189daed","owner":[],"postedDate":"January 23rd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-03-09T16:12:49+00:00","versionOfRecord":{"articleIdentity":"rs-8554000","link":"https://doi.org/10.1186/s12967-026-07977-7","journal":{"identity":"journal-of-translational-medicine","isVorOnly":false,"title":"Journal of Translational Medicine"},"publishedOn":"2026-03-05 15:58:55","publishedOnDateReadable":"March 5th, 2026"},"versionCreatedAt":"2026-01-23 21:29:04","video":"","vorDoi":"10.1186/s12967-026-07977-7","vorDoiUrl":"https://doi.org/10.1186/s12967-026-07977-7","workflowStages":[]},"version":"v1","identity":"rs-8554000","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8554000","identity":"rs-8554000","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}