Meta-Inflammation and Endotoxemia in a Highly Translational Porcine Model of Diet-Induced Obesity

Meta-Inflammation and Endotoxemia in a Highly Translational Porcine Model of Diet-Induced 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 Meta-Inflammation and Endotoxemia in a Highly Translational Porcine Model of Diet-Induced Obesity Betina Lyngfeldt Henriksen, Sofie Starbæk, Louise Brogaard, Eline Jessen, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4730631/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 06 Aug, 2025 Read the published version in Lab Animal → Version 1 posted You are reading this latest preprint version Abstract Meta-inflammation (chronic, low-grade systemic inflammation) is increasingly recognized as an essential link between obesity and the development of various non-communicable diseases. However, large animal models for studying obesity-related meta-inflammation are lacking. Minipigs have great potential as models for human diseases, warranting investigation of the performance of the Göttingen minipig as a model for obesity-associated meta-inflammation. Twenty-six pigs were fed a high fat, fructose, and cholesterol diet (HFFC) or a standard diet (SD) for 103 days, resulting in the HFFC group having a 45% higher body weight and 16% larger abdominal circumference by the end of the experiment. Meta-inflammation was shown in the HFFC group by elevated serum concentrations of the acute phase protein C-reactive protein for more than 60 days during development of obesity, accompanied by increased numbers of circulating neutrophils and monocytes. Additional obesity-related abnormalities included dyslipidemia, hepatosteatosis, and transcriptional changes to genes related to inflammation and metabolism in circulating leukocytes, liver, and visceral adipose tissue (VAT). Notably, transcription of genes related to lipid metabolism, namely ATP-binding cassette subfamily A member 1 (ABCA1) and ATP-binding cassette subfamily G member 1 (ABCG1), was elevated in liver, VAT, and circulating leukocytes (ABCA1 only) in the HFFC group compared to the SD group. Development of obesity was accompanied by endotoxemia, evidenced by a 2.5-fold increase in serum lipopolysaccharide concentration in the HFFC group compared to the SD group, suggesting increased intestinal permeability. In conclusion, the described Göttingen minipig model convincingly links diet-induced obesity, meta-inflammation, and endotoxemia, achieved by short-duration HFFC dieting. Health sciences/Diseases/Nutrition disorders/Obesity Health sciences/Medical research/Experimental models of disease Biological sciences/Immunology/Inflammation/Chronic inflammation Diet-induced chronic inflammation endotoxemia large animal model meta-inflammation obesity. Full Text Additional Declarations There is NO Competing Interest. Supplementary Files Supplementarymaterial.pdf Cite Share Download PDF Status: Published Journal Publication published 06 Aug, 2025 Read the published version in Lab Animal → 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-4730631","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":360745565,"identity":"3ec30eaa-05b6-41d1-a44e-d90262e335ef","order_by":0,"name":"Betina Lyngfeldt Henriksen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAApUlEQVRIiWNgGAWjYBACA3YGNiBlw9gAJCUbiNLCDNaSxthDqpbDJGgxZ+Yxe/Bxx3nZ/RIJjDdnEKPFspnH3HDmmdvGPRIJzJYbiHLYYR4zad6224lALWySD4jW8rftHKlaGNsOQLQQ5TDLZrYyyd62ZOOeMw+bLYnyvjl78zaJn212su3tyQdv9hCjhYGBwwDKACcAogD7A2JVjoJRMApGwUgFAKhPMMEi5JgLAAAAAElFTkSuQmCC","orcid":"","institution":"Technical University of Denmark","correspondingAuthor":true,"prefix":"","firstName":"Betina","middleName":"Lyngfeldt","lastName":"Henriksen","suffix":""},{"id":360745566,"identity":"82eb871d-7692-43d0-a11e-c82bf5607e85","order_by":1,"name":"Sofie Starbæk","email":"","orcid":"","institution":"Technical University of Denmark","correspondingAuthor":false,"prefix":"","firstName":"Sofie","middleName":"","lastName":"Starbæk","suffix":""},{"id":360745567,"identity":"c8a27490-8296-481a-8ded-460a917be653","order_by":2,"name":"Louise Brogaard","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Louise","middleName":"","lastName":"Brogaard","suffix":""},{"id":360745568,"identity":"c49a65af-ac6b-4111-801f-ce3c09e3ec67","order_by":3,"name":"Eline Jessen","email":"","orcid":"","institution":"Technical University of Denmark","correspondingAuthor":false,"prefix":"","firstName":"Eline","middleName":"","lastName":"Jessen","suffix":""},{"id":360745569,"identity":"9a20db77-a97c-404a-a23a-68b4cca91c08","order_by":4,"name":"Tim Jensen","email":"","orcid":"","institution":"University of Copenhagen","correspondingAuthor":false,"prefix":"","firstName":"Tim","middleName":"","lastName":"Jensen","suffix":""},{"id":360745570,"identity":"dd70c890-2c13-48ad-a2ae-91da5027e3c2","order_by":5,"name":"Steffen Goletz","email":"","orcid":"","institution":"Technical University of Denmark","correspondingAuthor":false,"prefix":"","firstName":"Steffen","middleName":"","lastName":"Goletz","suffix":""},{"id":360745571,"identity":"60f13255-9926-4603-9c11-2e1ed5f671b8","order_by":6,"name":"Peter M. H. Heegaard","email":"","orcid":"","institution":"Technical University of Denmark","correspondingAuthor":false,"prefix":"","firstName":"Peter","middleName":"M. H.","lastName":"Heegaard","suffix":""},{"id":360745572,"identity":"795e6922-a3a1-44bd-b28e-13a41f1bb07b","order_by":7,"name":"Kerstin Skovgaard","email":"","orcid":"","institution":"Technical University of Denmark","correspondingAuthor":false,"prefix":"","firstName":"Kerstin","middleName":"","lastName":"Skovgaard","suffix":""}],"badges":[],"createdAt":"2024-07-12 13:30:57","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4730631/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4730631/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41684-025-01588-3","type":"published","date":"2025-08-06T04:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":88508316,"identity":"b3d226c3-c460-48b4-944f-370435b9ed97","added_by":"auto","created_at":"2025-08-07 07:42:39","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1111293,"visible":true,"origin":"","legend":"","description":"","filename":"MetaInflammationandEndotoxemiaInaHighlyTranslationalPorcineModelofDietInducedObesity.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4730631/v1_covered_a1076061-1751-4e0f-80ba-8ad83412f6d5.pdf"},{"id":65822210,"identity":"bf5272a5-4fba-44a5-b8d9-9c3bf5f94c53","added_by":"auto","created_at":"2024-10-03 07:52:27","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":353667,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarymaterial.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4730631/v1/a3871cdc9a20a7263374a0d6.pdf"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"Meta-Inflammation and Endotoxemia in a Highly Translational Porcine Model of Diet-Induced Obesity","fulltext":[],"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":true,"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":" Diet-induced chronic inflammation, endotoxemia, large animal model, meta-inflammation, obesity.","lastPublishedDoi":"10.21203/rs.3.rs-4730631/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4730631/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Meta-inflammation (chronic, low-grade systemic inflammation) is increasingly recognized as an essential link between obesity and the development of various non-communicable diseases. However, large animal models for studying obesity-related meta-inflammation are lacking. Minipigs have great potential as models for human diseases, warranting investigation of the performance of the Göttingen minipig as a model for obesity-associated meta-inflammation. Twenty-six pigs were fed a high fat, fructose, and cholesterol diet (HFFC) or a standard diet (SD) for 103 days, resulting in the HFFC group having a 45% higher body weight and 16% larger abdominal circumference by the end of the experiment. Meta-inflammation was shown in the HFFC group by elevated serum concentrations of the acute phase protein C-reactive protein for more than 60 days during development of obesity, accompanied by increased numbers of circulating neutrophils and monocytes. Additional obesity-related abnormalities included dyslipidemia, hepatosteatosis, and transcriptional changes to genes related to inflammation and metabolism in circulating leukocytes, liver, and visceral adipose tissue (VAT). Notably, transcription of genes related to lipid metabolism, namely ATP-binding cassette subfamily A member 1 (ABCA1) and ATP-binding cassette subfamily G member 1 (ABCG1), was elevated in liver, VAT, and circulating leukocytes (ABCA1 only) in the HFFC group compared to the SD group. Development of obesity was accompanied by endotoxemia, evidenced by a 2.5-fold increase in serum lipopolysaccharide concentration in the HFFC group compared to the SD group, suggesting increased intestinal permeability. In conclusion, the described Göttingen minipig model convincingly links diet-induced obesity, meta-inflammation, and endotoxemia, achieved by short-duration HFFC dieting.","manuscriptTitle":"Meta-Inflammation and Endotoxemia in a Highly Translational Porcine Model of Diet-Induced Obesity","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-03 07:52:22","doi":"10.21203/rs.3.rs-4730631/v1","editorialEvents":[],"status":"published","journal":{"display":false,"email":"[email protected]","identity":"lab-animal","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"laban","sideBox":"Learn more about [Lab Animal](http://www.nature.com/laban/)","snPcode":"","submissionUrl":"","title":"Lab Animal","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature Research","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"14638476-92e2-4197-b9cb-9a9b8dd16afc","owner":[],"postedDate":"October 3rd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":38378523,"name":"Health sciences/Diseases/Nutrition disorders/Obesity"},{"id":38378524,"name":"Health sciences/Medical research/Experimental models of disease"},{"id":38378525,"name":"Biological sciences/Immunology/Inflammation/Chronic inflammation"}],"tags":[],"updatedAt":"2025-08-07T07:36:47+00:00","versionOfRecord":{"articleIdentity":"rs-4730631","link":"https://doi.org/10.1038/s41684-025-01588-3","journal":{"identity":"lab-animal","isVorOnly":false,"title":"Lab Animal"},"publishedOn":"2025-08-06 04:00:00","publishedOnDateReadable":"August 6th, 2025"},"versionCreatedAt":"2024-10-03 07:52:22","video":"","vorDoi":"10.1038/s41684-025-01588-3","vorDoiUrl":"https://doi.org/10.1038/s41684-025-01588-3","workflowStages":[]},"version":"v1","identity":"rs-4730631","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4730631","identity":"rs-4730631","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}