Relationship between obesity and iron metabolism: Insights from NHANES and Mendelian randomization studies

Relationship between obesity and iron metabolism: Insights from NHANES and Mendelian randomization studies | 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 Relationship between obesity and iron metabolism: Insights from NHANES and Mendelian randomization studies Jingjing Zhao, Hua Zhong, Jinjin Zhao, Guoqiang Wang, Zhaohui Wang, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4503071/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 Background Obesity is associated with various health and nutritional issues, including impaired iron metabolism. However, the causal relationship is debatable, and the connection between obesity and iron metabolism remains inconclusive. This study aimed to investigate the relationship between obesity and iron metabolism using an observational cohort study and Mendelian randomization (MR). Methods A total of 4,981 individuals were included in the cohort study after screening participants from the National Health and Nutrition Examination Survey (NHANES) cycles of 2003–2006 and 2017–2018. A multivariable linear regression model was used to analyze the association between body mass index (BMI) and iron metabolism indicators (serum iron [SI], serum ferritin [SF], transferrin saturation [TSAT], total iron binding capacity [TIBC], and soluble transferrin receptor [sTfR]). Then, a two-sample MR analysis was conducted to verify causality. Results The results showed that SI and TSAT were lower, while SF and sTfR were higher in the obesity group compared to normal-weight individuals. After adjusting for confounding factors in the multivariable linear regression models, BMI was found to be significantly negatively correlated with SI (β = -0.15, 95% CI: -0.17 to -0.12, P < 0.001) and TSAT (β = -0.23, 95% CI: -0.28 to -0.19, P < 0.001), and positively associated with SF (β = 0.57, 95% CI: -0.15 to 1.29, P = 0.120) and sTfR (β = 0.02, 95% CI: 0.02 to 0.03, P < 0.001). However, the difference between BMI and TIBC was not statistically significant (β = 0.02, 95% CI: -0.02 to 0.06, P = 0.328). The MR findings suggested that genetically predisposed BMI was linked to reduced levels of SI (β = -0.073, 95% CI: -0.140 to 0.004, P = 0.036) and TSAT (β = -0.11, 95% CI: -0.18 to -0.04, P = 0.001), and increased levels of SF (β = 0.14, 95% CI: 0.069 to 0.21, P = 0.035), but no causality between BMI and sTfR. Genetically determined iron levels did not show any association with BMI. Conclusion Although altered iron status may not increase the risk of obesity, a correlation and causal relationship between obesity and iron metabolism was observed. obesity iron metabolism National Health and Nutrition Examination Survey (NHANES) Mendelian randomization (MR) Full Text Additional Declarations No competing interests reported. Supplementary Files Additionalfile1.docx 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. 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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-4503071","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":312990398,"identity":"1f878a56-7579-4e56-b2c7-44dbce33fa24","order_by":0,"name":"Jingjing Zhao","email":"","orcid":"","institution":"The First Affiliated Hospital of Xinxiang Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jingjing","middleName":"","lastName":"Zhao","suffix":""},{"id":312990399,"identity":"bddf5170-0fbb-44f8-a2d1-6038926d0445","order_by":1,"name":"Hua Zhong","email":"","orcid":"","institution":"The First Affiliated Hospital of 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studies","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"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":"obesity, iron metabolism, National Health and Nutrition Examination Survey (NHANES), Mendelian randomization (MR)","lastPublishedDoi":"10.21203/rs.3.rs-4503071/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4503071/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eObesity is associated with various health and nutritional issues, including impaired iron metabolism. However, the causal relationship is debatable, and the connection between obesity and iron metabolism remains inconclusive. This study aimed to investigate the relationship between obesity and iron metabolism using an observational cohort study and Mendelian randomization (MR).\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA total of 4,981 individuals were included in the cohort study after screening participants from the National Health and Nutrition Examination Survey (NHANES) cycles of 2003\u0026ndash;2006 and 2017\u0026ndash;2018. A multivariable linear regression model was used to analyze the association between body mass index (BMI) and iron metabolism indicators (serum iron [SI], serum ferritin [SF], transferrin saturation [TSAT], total iron binding capacity [TIBC], and soluble transferrin receptor [sTfR]). Then, a two-sample MR analysis was conducted to verify causality.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe results showed that SI and TSAT were lower, while SF and sTfR were higher in the obesity group compared to normal-weight individuals. After adjusting for confounding factors in the multivariable linear regression models, BMI was found to be significantly negatively correlated with SI (β = -0.15, 95% CI: -0.17 to -0.12, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and TSAT (β = -0.23, 95% CI: -0.28 to -0.19, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and positively associated with SF (β\u0026thinsp;=\u0026thinsp;0.57, 95% CI: -0.15 to 1.29, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.120) and sTfR (β\u0026thinsp;=\u0026thinsp;0.02, 95% CI: 0.02 to 0.03, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). However, the difference between BMI and TIBC was not statistically significant (β\u0026thinsp;=\u0026thinsp;0.02, 95% CI: -0.02 to 0.06, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.328). The MR findings suggested that genetically predisposed BMI was linked to reduced levels of SI (β = -0.073, 95% CI: -0.140 to 0.004, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.036) and TSAT (β = -0.11, 95% CI: -0.18 to -0.04, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001), and increased levels of SF (β\u0026thinsp;=\u0026thinsp;0.14, 95% CI: 0.069 to 0.21, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.035), but no causality between BMI and sTfR. Genetically determined iron levels did not show any association with BMI.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eAlthough altered iron status may not increase the risk of obesity, a correlation and causal relationship between obesity and iron metabolism was observed.\u003c/p\u003e","manuscriptTitle":"Relationship between obesity and iron metabolism: Insights from NHANES and Mendelian randomization studies","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-12 19:51:18","doi":"10.21203/rs.3.rs-4503071/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":"688f2d42-b6a1-4ca9-9939-ddf03aba166b","owner":[],"postedDate":"June 12th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-09-09T11:54:35+00:00","versionOfRecord":[],"versionCreatedAt":"2024-06-12 19:51:18","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4503071","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4503071","identity":"rs-4503071","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}