Immune privilege of adipocyte mitochondria protects from obesity

Immune privilege of adipocyte mitochondria protects from obesity | 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 Immune privilege of adipocyte mitochondria protects from obesity Anh Cuong Hoang, Haidong Yu, Ya-Tin Lin, Jin-Chung Chen, Chia-Chun Chen, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-988599/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 28 Nov, 2022 Read the published version in Nature Metabolism → Version 1 posted You are reading this latest preprint version Abstract Infant nutrition is rich in lipids, and the adipose tissue has been adapted to properly break down neutral lipids and oxidize fatty acids in infancy. Accordingly, infant adipose tissue contains so-called beige adipocytes, which burn off lipids to heat, and impede fat storage and obesity. We show here that infant adipocytes are immune privileged sites for mitochondria due to a blockade in interferon regulatory factor 7 (IRF7)-signaling, which allows mitochondrial RNA to trigger beige adipocyte differentiation through mitochondria-to-nucleus signaling. These mechanisms serve to maintain an extensive mitochondrial network in beige adipocytes and protect against obesity. By contrast, fat storing white adipocytes lack these mechanisms and respond to their mitochondrial content with inflammation. We show that obesity subverts the immune privilege for mitochondria in adipocytes, which reduces mitochondrial mass and abrogates beige adipocyte development. In turn, suppressing IRF7 signaling and restoring the RNA-mediated mitochondria-to-nucleus signaling in adipocytes effectively reduces obesity. Immunology Endocrinology & Metabolism innate immunity obesity interferons IFI16 vitamin D Full Text Additional Declarations There is NO Competing Interest. Supplementary Files HoangSupplementaryInformation.pdf Supplementary Information Cite Share Download PDF Status: Published Journal Publication published 28 Nov, 2022 Read the published version in Nature Metabolism → 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-988599","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":60860956,"identity":"8316e0bc-2f61-4b8d-b947-339ae4be73ee","order_by":0,"name":"Anh Cuong Hoang","email":"","orcid":"","institution":"Ulm University","correspondingAuthor":false,"prefix":"","firstName":"Anh","middleName":"Cuong","lastName":"Hoang","suffix":""},{"id":60860957,"identity":"1558866f-b7bc-4899-a0c7-b91c5b9f1e5a","order_by":1,"name":"Haidong Yu","email":"","orcid":"","institution":"Ulm University","correspondingAuthor":false,"prefix":"","firstName":"Haidong","middleName":"","lastName":"Yu","suffix":""},{"id":60860958,"identity":"4b21820a-9305-402d-8abb-a3513681ab73","order_by":2,"name":"Ya-Tin Lin","email":"","orcid":"https://orcid.org/0000-0001-7910-1223","institution":"Chang Gung University","correspondingAuthor":false,"prefix":"","firstName":"Ya-Tin","middleName":"","lastName":"Lin","suffix":""},{"id":60860959,"identity":"d2454998-e978-424e-a11a-0a407eff95c6","order_by":3,"name":"Jin-Chung Chen","email":"","orcid":"","institution":"Chang Gung University","correspondingAuthor":false,"prefix":"","firstName":"Jin-Chung","middleName":"","lastName":"Chen","suffix":""},{"id":60860960,"identity":"42198674-a3bb-4013-b626-7b6f1d8c2d70","order_by":4,"name":"Chia-Chun Chen","email":"","orcid":"","institution":"Chang Gung University","correspondingAuthor":false,"prefix":"","firstName":"Chia-Chun","middleName":"","lastName":"Chen","suffix":""},{"id":60860961,"identity":"d42382de-5e74-4312-a558-96040e450915","order_by":5,"name":"Victoria Diedrich","email":"","orcid":"","institution":"Ulm University","correspondingAuthor":false,"prefix":"","firstName":"Victoria","middleName":"","lastName":"Diedrich","suffix":""},{"id":60860962,"identity":"d37287ed-e11c-451a-8ea0-b1821e528043","order_by":6,"name":"Annika Herwig","email":"","orcid":"","institution":"Ulm University","correspondingAuthor":false,"prefix":"","firstName":"Annika","middleName":"","lastName":"Herwig","suffix":""},{"id":60860963,"identity":"da8b2570-be7e-42fa-9631-b76f0b1160aa","order_by":7,"name":"Kathrin Landgraf","email":"","orcid":"https://orcid.org/0000-0002-6878-6033","institution":"University of Leipzig, Pediatric Research Centre, Department of Women’s and Child Health","correspondingAuthor":false,"prefix":"","firstName":"Kathrin","middleName":"","lastName":"Landgraf","suffix":""},{"id":60860964,"identity":"ed3cd938-ca8a-4de1-b66a-5ce1b7f41db5","order_by":8,"name":"Antje Körner","email":"","orcid":"https://orcid.org/0000-0001-6001-0356","institution":"Center for Pediatric Research Leipzig (CPL), University Hospital for Children \u0026 Adolescents, University of Leipzig, Leipzig","correspondingAuthor":false,"prefix":"","firstName":"Antje","middleName":"","lastName":"Körner","suffix":""},{"id":60860965,"identity":"bd7b2560-2b3a-492c-9f92-0e1e5e432c8d","order_by":9,"name":"Tamás Roszer","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9klEQVRIiWNgGAWjYPCDCgYGNgYGxgMMDMw41fCgcs+AtTCQoIWxDULj1WLPfjrx4w+Ge3L8/McfPq6cdziPj4HH4NANBms5nLbw5G6W5mEoNpackZBseHbb4WI2oJbDOQzpxrgdlrtBmoEhIXHDDYZjko3bDie2yb8BaTmc2IBLC//bzT9/ALXsP3+w/WfjHKAWiC2H63FqkcjdJsEDsoUhmY2xsQGhJQGnw2683WbNY5BgLHEjjVmy4Vg6UAtbweEcg3RDXLaw9+duvvmjIkGOv//4w48NNdaJ8xuYNz7OqbCWx2ULBBgQITIKRsEoGAWjgAQAAFcYUls4V+tPAAAAAElFTkSuQmCC","orcid":"","institution":"Ulm University","correspondingAuthor":true,"prefix":"","firstName":"Tamás","middleName":"","lastName":"Roszer","suffix":""}],"badges":[],"createdAt":"2021-10-18 06:45:40","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-988599/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-988599/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s42255-022-00683-w","type":"published","date":"2022-11-28T05:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":29636841,"identity":"064b2aea-8d25-4ca3-9c07-5c9574fd8616","added_by":"auto","created_at":"2022-11-29 08:09:05","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3706272,"visible":true,"origin":"","legend":"Article File","description":"","filename":"Hoangetal18Oct2021combinedfiles.pdf","url":"https://assets-eu.researchsquare.com/files/rs-988599/v1_covered.pdf"},{"id":15225288,"identity":"c20111d8-ba9d-456b-a4b1-380ddec087b8","added_by":"auto","created_at":"2021-11-04 15:55:28","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3694560,"visible":true,"origin":"","legend":"Article File","description":"","filename":"Hoangetal18Oct2021combinedfiles.pdf","url":"https://assets-eu.researchsquare.com/files/rs-988599/v1_covered.pdf"},{"id":15225287,"identity":"7582c0c9-7ee1-4db9-8255-0553c7e2d2bf","added_by":"auto","created_at":"2021-11-04 15:55:20","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":3217626,"visible":true,"origin":"","legend":"Supplementary Information","description":"","filename":"HoangSupplementaryInformation.pdf","url":"https://assets-eu.researchsquare.com/files/rs-988599/v1/e6af59797b1a4f039064c86c.pdf"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"Immune privilege of adipocyte mitochondria protects from obesity","fulltext":[{"header":"Full Text","content":"This preprint is available for \u003ca href='/article/rs-988599/latest.pdf' target='_blank'\u003edownload as a PDF\u003c/a\u003e."}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"nature-portfolio","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Nature Portfolio","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"ejp","reportingPortfolio":"","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":" innate immunity, obesity, interferons, IFI16, vitamin D","lastPublishedDoi":"10.21203/rs.3.rs-988599/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-988599/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Infant nutrition is rich in lipids, and the adipose tissue has been adapted to properly break down neutral lipids and oxidize fatty acids in infancy. Accordingly, infant adipose tissue contains so-called beige adipocytes, which burn off lipids to heat, and impede fat storage and obesity. We show here that infant adipocytes are immune privileged sites for mitochondria due to a blockade in interferon regulatory factor 7 (IRF7)-signaling, which allows mitochondrial RNA to trigger beige adipocyte differentiation through mitochondria-to-nucleus signaling. These mechanisms serve to maintain an extensive mitochondrial network in beige adipocytes and protect against obesity. By contrast, fat storing white adipocytes lack these mechanisms and respond to their mitochondrial content with inflammation. We show that obesity subverts the immune privilege for mitochondria in adipocytes, which reduces mitochondrial mass and abrogates beige adipocyte development. In turn, suppressing IRF7 signaling and restoring the RNA-mediated mitochondria-to-nucleus signaling in adipocytes effectively reduces obesity.","manuscriptTitle":"Immune privilege of adipocyte mitochondria protects from obesity","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-11-04 15:55:17","doi":"10.21203/rs.3.rs-988599/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"nature-metabolism","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"natmetab","sideBox":"Learn more about [Nature Metabolism](http://www.nature.com/natmetab/)","snPcode":"","submissionUrl":"","title":"Nature Metabolism","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature Research","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"54c994c5-3595-4d87-a8ae-183801477bd7","owner":[],"postedDate":"November 4th, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":8319207,"name":"Immunology"},{"id":8319208,"name":"Endocrinology \u0026 Metabolism"}],"tags":[],"updatedAt":"2022-11-29T08:08:52+00:00","versionOfRecord":{"articleIdentity":"rs-988599","link":"https://doi.org/10.1038/s42255-022-00683-w","journal":{"identity":"nature-metabolism","isVorOnly":false,"title":"Nature Metabolism"},"publishedOn":"2022-11-28 05:00:00","publishedOnDateReadable":"November 28th, 2022"},"versionCreatedAt":"2021-11-04 15:55:17","video":"","vorDoi":"10.1038/s42255-022-00683-w","vorDoiUrl":"https://doi.org/10.1038/s42255-022-00683-w","workflowStages":[]},"version":"v1","identity":"rs-988599","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-988599","identity":"rs-988599","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}