The regulatory role of the n-6/n-3 ratio in intestinal barrier function and glucose and lipid metabolism disorders

The regulatory role of the n-6/n-3 ratio in intestinal barrier function and glucose and lipid metabolism disorders | 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 The regulatory role of the n-6/n-3 ratio in intestinal barrier function and glucose and lipid metabolism disorders Luca Moretti, Anna Kovács, Erik M. Lindberg This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7997486/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 An unbalanced intake of n-6 and n-3 polyunsaturated fatty acids (PUFAs) can damage the gut barrier and disturb metabolism. This study used a high-fat diet mouse model of diabetes to examine the effects of different n-6/n-3 ratios (20:1, 10:1, and 4:1). Mice were fed the test diets for 12 weeks. When the ratio was reduced to 4:1, villus height and tight-junction protein levels increased by about 50%. Plasma lipopolysaccharide (LPS) dropped by 42%, and the HOMA-IR index decreased by 32%. The gut microbiota also changed, showing more Bifidobacterium and Bacteroides in the 4:1 group. These results indicate that a lower n-6/n-3 ratio supports the intestinal barrier, lowers endotoxin levels, and improves insulin sensitivity. The study suggests that keeping an n-6/n-3 ratio near 4:1 may help control inflammation and reduce metabolic problems linked to diabetes. General Cell Biology & Physiology Applied Biochemistry n-6/n-3 ratio gut barrier lipopolysaccharide tight-junction proteins insulin resistance gut microbiota diabetes Full Text Additional Declarations The authors declare no competing interests. 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-7997486","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":538001652,"identity":"6cec8dda-7042-4770-9f47-4dc3f75517be","order_by":0,"name":"Luca Moretti","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA1ElEQVRIiWNgGAWjYJCCgx8MJHjsjzcAmQYWxGk5LFFgIcNw5gBIiwSR1vB8qLBhuJEAYhKhxeBG8sEDEkCHMc58fnXDjwIJBv727gQCWtISDhQAtTBL55Td7AE6TOLM2Q14tZjdzjEA28ImnZN2gweoxUAil5CW/A8HgCp5eCTPpN38Q5yWHAawFgkJ9mO3ibLF/v4zg8Mghxnw5LDdlgHpJeQXyZ7Djz9++FNnb8B+/NnNN39s5Pjbe/FrQQI8BmCSWOUgwP6AFNWjYBSMglEwggAAZcxGvUe08xYAAAAASUVORK5CYII=","orcid":"","institution":"Department of Clinical Medicine, Lund University, Lund SE-221 00, Sweden","correspondingAuthor":true,"prefix":"","firstName":"Luca","middleName":"","lastName":"Moretti","suffix":""},{"id":538001653,"identity":"14eac279-31fe-4b6e-b787-e68e5a1272be","order_by":1,"name":"Anna Kovács","email":"","orcid":"","institution":"Department of Clinical Medicine, Lund University, Lund SE-221 00, Sweden","correspondingAuthor":false,"prefix":"","firstName":"Anna","middleName":"","lastName":"Kovács","suffix":""},{"id":538001654,"identity":"48f89005-ea9c-4b08-95a3-73435932f2f8","order_by":2,"name":"Erik M. Lindberg","email":"","orcid":"","institution":"Department of Clinical Medicine, Lund University, Lund SE-221 00, Sweden","correspondingAuthor":false,"prefix":"","firstName":"Erik","middleName":"M.","lastName":"Lindberg","suffix":""}],"badges":[],"createdAt":"2025-10-31 10:37:56","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-7997486/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7997486/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":94988890,"identity":"d4237e40-9494-47d5-84de-21b84c59f091","added_by":"auto","created_at":"2025-11-03 07:11:17","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":731039,"visible":true,"origin":"","legend":"","description":"","filename":"10.2805yawenTheregulatoryroleofthen6n3ratioinintestinalbarrierfunctionandglucoseandlipidmetabolismdisorders.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7997486/v1_covered_a32c0a4a-c1aa-48b0-b01b-6b4b8ddd016e.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eThe regulatory role of the n-6/n-3 ratio in intestinal barrier function and glucose and lipid metabolism disorders\u003c/strong\u003e\u003c/p\u003e","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"n-6/n-3 ratio, gut barrier, lipopolysaccharide, tight-junction proteins, insulin resistance, gut microbiota, diabetes","lastPublishedDoi":"10.21203/rs.3.rs-7997486/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7997486/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eAn unbalanced intake of n-6 and n-3 polyunsaturated fatty acids (PUFAs) can damage the gut barrier and disturb metabolism. This study used a high-fat diet mouse model of diabetes to examine the effects of different n-6/n-3 ratios (20:1, 10:1, and 4:1). Mice were fed the test diets for 12 weeks. When the ratio was reduced to 4:1, villus height and tight-junction protein levels increased by about 50%. Plasma lipopolysaccharide (LPS) dropped by 42%, and the HOMA-IR index decreased by 32%. The gut microbiota also changed, showing more \u003cem\u003eBifidobacterium\u003c/em\u003e\u0026nbsp;and \u003cem\u003eBacteroides\u003c/em\u003e\u0026nbsp;in the 4:1 group. These results indicate that a lower n-6/n-3 ratio supports the intestinal barrier, lowers endotoxin levels, and improves insulin sensitivity. The study suggests that keeping an n-6/n-3 ratio near 4:1 may help control inflammation and reduce metabolic problems linked to diabetes.\u003c/p\u003e","manuscriptTitle":"The regulatory role of the n-6/n-3 ratio in intestinal barrier function and glucose and lipid metabolism disorders","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-03 02:42:26","doi":"10.21203/rs.3.rs-7997486/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"1de49bdd-6527-4151-bae4-395247035b62","owner":[],"postedDate":"November 3rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":57219148,"name":"General Cell Biology \u0026 Physiology"},{"id":57219149,"name":"Applied Biochemistry"}],"tags":[],"updatedAt":"2025-11-03T02:42:26+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-03 02:42:26","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7997486","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7997486","identity":"rs-7997486","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}