LPS stimulating upregulates lipid accumulation in mice liver dependent on STAT1/APOE axis signaling pathway.

LPS stimulating upregulates lipid accumulation in mice liver dependent on STAT1/APOE axis signaling pathway. | 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 LPS stimulating upregulates lipid accumulation in mice liver dependent on STAT1/APOE axis signaling pathway. Zhongnan Ma, Jianqiang Xu, Yuanyuan Zhu, Kongjunyi Duan, Liwen Zhang, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6214389/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 Lipid metabolism plays a crucial role in maintaining metabolic homeostasis, and its dysregulation is implicated in various disorders. Recent studies have shown that inflammation, particularly that induced by bacterial endotoxins like lipopolysaccharide (LPS), can significantly impact lipid metabolism. However, the mechanisms by which LPS modulates lipid metabolism remain unclear, and the crosstalk between inflammatory signaling and lipid regulatory pathways is not fully understood. To address this gap, this study investigates the effects of LPS on lipid metabolism using animal models. By examining the molecular and physiological responses to LPS exposure, we identify the STAT1/APOE axis as a key pathway through which LPS influences lipid metabolism. Our findings suggest that LPS stimulation enhances lipid metabolism via this axis, providing new insights into the metabolic effects of inflammatory signaling. Notably, our results also highlight an intriguing aspect: short-term LPS exposure may exert beneficial effects on metabolic signaling, challenging the traditional view that inflammation is solely detrimental to metabolism. These findings contribute to a deeper understanding of the relationship between inflammation and lipid metabolism and may have implications for metabolic disease research and therapeutic strategies. Biological sciences/Immunology/Inflammation/Acute inflammation Biological sciences/Cell biology/Cell signalling/Lipid signalling Biological sciences/Cell biology/Cell signalling Lipopolysaccharide lipid metabolism Inflammation Signal Transducer and Activator of Transcription 1 (STAT1) Apolipoprotein E (APOE) Figures Figure 1 Figure 2 Figure 3 Figure 4 Full Text Additional Declarations (Not answered) Supplementary Files sFigure20250311.pdf Supplementary Figure 1 to Figure 3 Unprocessedimage20250312.pdf Unprocessed image 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. 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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-6214389","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":440678169,"identity":"63eb7fc1-c440-4a5d-9971-e0773225a476","order_by":0,"name":"Zhongnan Ma","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAo0lEQVRIiWNgGAWjYJACg4QKtgQQTbyWggdnSNXy8WEbAwla5KcdfrghcR5fHgN78zYJorQwzk4zNkjcxlbMwHOsjDgtzNIJZiAtiQ0SOWbEaWGTTv/+I3EOUIv8GyK18EjnGBgkNoBs4SFSi4R0ToFBwjG2xDaetGILorTIz07fYPij5lhiP/vhjTeI0gIFxxjYSFEOAjWkahgFo2AUjIKRBABjfis1xJIUgwAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0003-1457-0330","institution":"Johns Hopkins University","correspondingAuthor":true,"prefix":"","firstName":"Zhongnan","middleName":"","lastName":"Ma","suffix":""},{"id":440678170,"identity":"f10fb57c-123c-4227-990f-90ba70a9c475","order_by":1,"name":"Jianqiang Xu","email":"","orcid":"","institution":"Southern University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Jianqiang","middleName":"","lastName":"Xu","suffix":""},{"id":440678171,"identity":"c1e76b81-b215-4998-9f9b-444b4166dd83","order_by":2,"name":"Yuanyuan Zhu","email":"","orcid":"","institution":"Anhui University of Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yuanyuan","middleName":"","lastName":"Zhu","suffix":""},{"id":440678172,"identity":"3d469b9a-15d7-4b2b-a2d5-76b15b51bbfc","order_by":3,"name":"Kongjunyi Duan","email":"","orcid":"","institution":"Hefei Comprehensive National Science Center","correspondingAuthor":false,"prefix":"","firstName":"Kongjunyi","middleName":"","lastName":"Duan","suffix":""},{"id":440678173,"identity":"0d19d818-e434-405a-8b3e-bbf5ae083cae","order_by":4,"name":"Liwen Zhang","email":"","orcid":"","institution":"Anhui Agricultural University","correspondingAuthor":false,"prefix":"","firstName":"Liwen","middleName":"","lastName":"Zhang","suffix":""},{"id":440678174,"identity":"c411ebec-39b2-4ca4-9c8f-9494d1b22650","order_by":5,"name":"Meng Wang","email":"","orcid":"","institution":"Hefei Comprehensive National Science Center","correspondingAuthor":false,"prefix":"","firstName":"Meng","middleName":"","lastName":"Wang","suffix":""},{"id":440678175,"identity":"f6382242-38a2-4cd8-991b-f0e6e3945ff5","order_by":6,"name":"Chao Zhang","email":"","orcid":"","institution":"Anhui Agricultural University","correspondingAuthor":false,"prefix":"","firstName":"Chao","middleName":"","lastName":"Zhang","suffix":""},{"id":440678176,"identity":"30af161d-76e5-40e0-85f6-d6637ec1616f","order_by":7,"name":"Yu Wang","email":"","orcid":"","institution":"Anhui University of Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yu","middleName":"","lastName":"Wang","suffix":""},{"id":440678177,"identity":"d753a58e-ca5b-4b60-b15f-9c465051432b","order_by":8,"name":"Heng Zhang","email":"","orcid":"","institution":"Shanghai Jiaotong University","correspondingAuthor":false,"prefix":"","firstName":"Heng","middleName":"","lastName":"Zhang","suffix":""},{"id":440678178,"identity":"981aa874-3674-4d40-8939-409e26c21aea","order_by":9,"name":"Jiaxuan Feng","email":"","orcid":"","institution":"Shanghai Jiaotong University","correspondingAuthor":false,"prefix":"","firstName":"Jiaxuan","middleName":"","lastName":"Feng","suffix":""},{"id":440678179,"identity":"5e7bf788-2f2f-4047-b439-79b05ebe0092","order_by":10,"name":"Anhua Lei","email":"","orcid":"","institution":"Hefei Comprehensive National Science Center","correspondingAuthor":false,"prefix":"","firstName":"Anhua","middleName":"","lastName":"Lei","suffix":""}],"badges":[],"createdAt":"2025-03-12 18:45:46","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6214389/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6214389/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":80310850,"identity":"ba924a90-ede3-48d9-a53d-26b84d0f1064","added_by":"auto","created_at":"2025-04-10 11:21:27","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":627719,"visible":true,"origin":"","legend":"\u003cp\u003eCharacterization of a mouse model design. (A) Specific procedure for the administration of LPS to mice. (B) Weight and appearance changes in the liver and spleen of mice after LPS stimulation were observed (n=6). (C) Hematoxylin and eosin staining showing changes in the spleen and liver before and after LPS stimulation.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6214389/v1/27c9a2f6a1889e72064ceddb.png"},{"id":80310554,"identity":"5e225fa9-5c21-4981-83eb-86339c0a1e3e","added_by":"auto","created_at":"2025-04-10 11:13:27","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":382127,"visible":true,"origin":"","legend":"\u003cp\u003eLPS stimulating leads to upregulate lipid metabolism. (A) The concentrations of serum cholesterol and triglycerides at 4 hours and 24 hours after LPS stimulation (n=6). (B) The activity of GOT enzyme and GPT enzyme in serum (n=6). (C) The activity of GOT enzyme and GPT enzyme in liver tissue (n=6). (D) Representative picture of liver sections with Oil Red O staining and statistics (n=3).\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6214389/v1/dbfe79f03432c1e20fb8c232.png"},{"id":80309789,"identity":"bdb22199-959e-4f6e-80a9-4d802be00d2b","added_by":"auto","created_at":"2025-04-10 11:05:27","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":491150,"visible":true,"origin":"","legend":"\u003cp\u003eSTAT1 signaling were highly active in liver and spleen. (A) The protein expression level of pS473-AKT, AKT, pS536-NFKB, NFKB, pY701-STAT1, STAT1 in spleen tissue. (B) The protein expression level of pS473-AKT, AKT, pS536-NFKB, NFKB, pY701-STAT1, STAT1 in liver tissue, GAPDH as internal control. (C) Representative picture of immunohistochemistry of pY701-STAT1 in spleen and liver tissue. (D) the statistic of figure 3C (n=3).\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-6214389/v1/f2174cd034d03cba47bc1db4.png"},{"id":80309793,"identity":"576f5593-0573-4616-a7cc-5c51a69504a4","added_by":"auto","created_at":"2025-04-10 11:05:27","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":295678,"visible":true,"origin":"","legend":"\u003cp\u003eKnockout STAT1 can rescue LPS-induced Lipid accumulation through APOE in liver. (A) The concentrations of serum cholesterol and triglycerides after LPS stimulation for 24 hours in wild type mice and STAT1-KO mice (n=12). (B) The protein expression level of STAT1, pS473-AKT, AKT, pS536-NFKBp65, NFKBp65, ABCA1, APOE in liver tissue (n=3). (C) The protein expression level of STAT1, pS473-AKT, AKT, pS536-NFKBp65, NFKBp65, ABCA1, APOE in spleen tissue (n=3). (D) The weight and appearance in the liver and spleen in STAT1-KO mice (n=3) and statistic.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-6214389/v1/04c397fdc819587b291076f7.png"},{"id":80311508,"identity":"32b2a95d-711e-4dee-8407-35002072b9d4","added_by":"auto","created_at":"2025-04-10 11:29:29","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":644040,"visible":true,"origin":"","legend":"Article File","description":"","filename":"ManuscriptLPSSTAT120250302.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6214389/v1_covered_f5acd973-95b4-43ef-9aa5-ee834ae5f30b.pdf"},{"id":80309795,"identity":"f7e31955-a241-464c-9231-f224f6ff6068","added_by":"auto","created_at":"2025-04-10 11:05:27","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":2762654,"visible":true,"origin":"","legend":"Supplementary Figure 1 to Figure 3","description":"","filename":"sFigure20250311.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6214389/v1/f048ccb6fb7fb96c5a1f24f7.pdf"},{"id":80309800,"identity":"5e6d6818-f790-40d7-8dcc-32cecb7e4000","added_by":"auto","created_at":"2025-04-10 11:05:28","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":47551178,"visible":true,"origin":"","legend":"Unprocessed image","description":"","filename":"Unprocessedimage20250312.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6214389/v1/3c55ed4d3fc5bfa49974c33d.pdf"}],"financialInterests":"(Not answered)","formattedTitle":"LPS stimulating upregulates lipid accumulation in mice liver dependent on\nSTAT1/APOE axis signaling pathway.","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":"Lipopolysaccharide, lipid metabolism, Inflammation, Signal Transducer and Activator of Transcription 1 (STAT1), Apolipoprotein E (APOE)","lastPublishedDoi":"10.21203/rs.3.rs-6214389/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6214389/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Lipid metabolism plays a crucial role in maintaining metabolic homeostasis, and its dysregulation is implicated in various disorders. Recent studies have shown that inflammation, particularly that induced by bacterial endotoxins like lipopolysaccharide (LPS), can significantly impact lipid metabolism. However, the mechanisms by which LPS modulates lipid metabolism remain unclear, and the crosstalk between inflammatory signaling and lipid regulatory pathways is not fully understood. To address this gap, this study investigates the effects of LPS on lipid metabolism using animal models. By examining the molecular and physiological responses to LPS exposure, we identify the STAT1/APOE axis as a key pathway through which LPS influences lipid metabolism. Our findings suggest that LPS stimulation enhances lipid metabolism via this axis, providing new insights into the metabolic effects of inflammatory signaling. Notably, our results also highlight an intriguing aspect: short-term LPS exposure may exert beneficial effects on metabolic signaling, challenging the traditional view that inflammation is solely detrimental to metabolism. These findings contribute to a deeper understanding of the relationship between inflammation and lipid metabolism and may have implications for metabolic disease research and therapeutic strategies.","manuscriptTitle":"LPS stimulating upregulates lipid accumulation in mice liver dependent on\nSTAT1/APOE axis signaling pathway.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-10 11:05:22","doi":"10.21203/rs.3.rs-6214389/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":"75bfe22d-e16a-4796-b290-53a6091ce932","owner":[],"postedDate":"April 10th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":46918249,"name":"Biological sciences/Immunology/Inflammation/Acute inflammation"},{"id":46918250,"name":"Biological sciences/Cell biology/Cell signalling/Lipid signalling"},{"id":46918251,"name":"Biological sciences/Cell biology/Cell signalling"}],"tags":[],"updatedAt":"2025-04-10T11:05:22+00:00","versionOfRecord":[],"versionCreatedAt":"2025-04-10 11:05:22","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6214389","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6214389","identity":"rs-6214389","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}