Single Head-Neck Irradiation Intervention Increases Thyroid Hormone Level and Enhances Energy Metabolism in High-Fat Diet Mice

Single Head-Neck Irradiation Intervention Increases Thyroid Hormone Level and Enhances Energy Metabolism in High-Fat Diet Mice | 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 Single Head-Neck Irradiation Intervention Increases Thyroid Hormone Level and Enhances Energy Metabolism in High-Fat Diet Mice Qian Lin, Caishun Zhang, Manwen Li, Haidan Wang, Kaizhen Su, Defeng Liu, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-121920/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 Radiotherapy, an established treatment of malignant diseases of the head and neck, increases the risk of chronic metabolic disorders. However, the molecular mechanisms responsible for metabolic dysfunction after irradiation remain unknown. We aimed to determine whether single head-neck irradiation intervention changes the levels of thyroid hormones and affects energy metabolism in high-fat diet mice and in chow diet mice. C57BL/6 mice were treated with a single dose of 6 Gy X-ray head-neck irradiation and were fed a high-fat diet. Body weight, accumulated food intake, fasting blood glucose and glucose tolerance were measured during the study. Plasma, brown adipose tissue, thyroid, liver and white adipose tissue were collected for histological analysis. We found that head-neck irradiation significantly increased food intake and decreased body weight in high-fat diet mice. However, there were no obvious changes in chow diet mice. Further studies showed that head-neck irradiation significantly increased levels of 3,5,3’-triiodothyronine and thyroid-stimulating hormone, as well as expression of uncoupling protein 1 in brown adipose tissue and glucose transporter 2 in liver in high-fat diet mice. Our results suggest that single head-neck irradiation intervention increases thyroid hormones levels and enhances energy metabolism in high-fat diet mice. Endocrinology & Metabolism Animal Science head-neck irradiation HFD TH energy metabolism Ucp-1 GLUT2 Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Full Text Supplementary Files SupplementaryInformation.pdf 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-121920","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":6426975,"identity":"0dd7cc43-23c4-4b66-bc10-848c4283d950","order_by":0,"name":"Qian Lin","email":"","orcid":"","institution":"Qingdao University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Qian","middleName":"","lastName":"Lin","suffix":""},{"id":6426976,"identity":"5530972d-4d06-42e2-b4e2-00a7fe029690","order_by":1,"name":"Caishun Zhang","email":"","orcid":"","institution":"Qingdao University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Caishun","middleName":"","lastName":"Zhang","suffix":""},{"id":6426977,"identity":"e3d410ba-54a8-44bc-976d-9769f32676d0","order_by":2,"name":"Manwen Li","email":"","orcid":"","institution":"Qingdao University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Manwen","middleName":"","lastName":"Li","suffix":""},{"id":6426978,"identity":"f6080f5e-5f94-40e0-b172-5d5fe38a9712","order_by":3,"name":"Haidan Wang","email":"","orcid":"","institution":"Qingdao University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Haidan","middleName":"","lastName":"Wang","suffix":""},{"id":6426979,"identity":"8588ad87-b18e-4db3-a06b-ef39fdb701ed","order_by":4,"name":"Kaizhen Su","email":"","orcid":"","institution":"Qingdao University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Kaizhen","middleName":"","lastName":"Su","suffix":""},{"id":6426980,"identity":"e7ec0525-28df-471a-a16c-5ca121ebbd58","order_by":5,"name":"Defeng Liu","email":"","orcid":"","institution":"Qingdao University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Defeng","middleName":"","lastName":"Liu","suffix":""},{"id":6426981,"identity":"f520acb9-30b9-4b9e-a138-86b5a5d99a0d","order_by":6,"name":"Jvchen Zhang","email":"","orcid":"","institution":"Affiliated Hospital of Qingdao University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jvchen","middleName":"","lastName":"Zhang","suffix":""},{"id":6426982,"identity":"e26a14a4-0932-4224-b8a5-2bec62123861","order_by":7,"name":"Peng Jiang","email":"","orcid":"","institution":"Affiliated Hospital of Qingdao University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Peng","middleName":"","lastName":"Jiang","suffix":""},{"id":6426983,"identity":"75793525-ccaf-4761-9391-80f1dfeb87de","order_by":8,"name":"Peige Wang","email":"","orcid":"","institution":"Affiliated Hospital of Qingdao University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Peige","middleName":"","lastName":"Wang","suffix":""},{"id":6426984,"identity":"889f514f-82b6-424c-ad93-12c790e188d4","order_by":9,"name":"Jing Dong","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5klEQVRIiWNgGAWjYDCCA0AsYcDAwM/eA+bz8BGtRbLnDJjDw0aUFhAwmJED4RDUwne89/ALi4I7dhsk3x58/DHHToaNgfnhoxt4tEieOZdmIWHwLHm7dF6ywcFtyUCHsRkb5+DRYnAjx8xAwuBwsuXsHDOJg9uYgVp42KSJ0mJw8wxISz1RWowfALXYGdzgAWk5TFiL5JkzZsBAPpwg2ZNjbHB223EeNmYCfuE73mP8WeLPYXt+9jOGDyq3VQMZzQ8f49MCBGzSEgwMiQ1wPjN+5WAlHz8wMNgTVjcKRsEoGAUjFgAAU89KZHGFPQwAAAAASUVORK5CYII=","orcid":"","institution":"Qingdao University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Jing","middleName":"","lastName":"Dong","suffix":""}],"badges":[],"createdAt":"2020-12-04 14:58:59","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-121920/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-121920/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":4276014,"identity":"52076dcc-afa7-4c7a-8132-2d9ed7947022","added_by":"auto","created_at":"2020-12-15 17:15:46","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":91001,"visible":true,"origin":"","legend":"Single head-neck irradiation intervention decreases body weight and increases accumulated food intake in HFD mice. (a): Changes in body weight over 10 weeks. (b): Gross morphology. (c): Cumulative weights of food intake were counted 9 weeks post irradiation. (d): Cumulative calories of food intake were counted 9 weeks post irradiation. Data are presented as means ± SEM (Ctrl+CD: n = 4; Irr+CD: n = 6;\nCtrl+HFD: n =7; Irr+HFD: n = 8). *P \u003c 0.05 for the effect of irradiated mice fed an HFD vs. non-irradiated mice fed an HFD, #P \u003c 0.05 for the effect of irradiated mice fed an HFD vs. irradiated mice fed a CD, ##P \u003c 0.01 for the effect of irradiated mice fed an HFD vs. irradiated mice fed a CD. Ctrl, non-irradiated; Irr, Irradiated; CD, chow diet; HFD, high-fat diet.","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-121920/v1/abd006cdd1c13c7179492d7a.jpg"},{"id":4276015,"identity":"0601fbb9-c119-48e9-a13f-16ed01626af3","added_by":"auto","created_at":"2020-12-15 17:15:46","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":73140,"visible":true,"origin":"","legend":"Effects of single head-neck irradiation intervention on the structure of thyroid follicles and TH levels. (a): Fresh thyroid samples. (b): H\u0026E staining of thyroid follicles (400×). (c): Plasma T3 levels measured using a Mouse T3 ELISA Kit. (d): Plasma TSH levels measured using a Mouse TSH ELISA Kit. Data are presented as means ± SEM (Ctrl+CD: n = 3; Irr+CD: n = 3; Ctrl+HFD: n =3; Irr+HFD: n = 3). *P \u003c 0.05 for the effect of\nirradiated mice fed an HFD vs. non-irradiated mice fed a HFD, ^P \u003c 0.05 for the effect of non-irradiated mice fed an HFD vs. non-irradiated mice fed a CD. Ctrl, non-irradiated; Irr, Irradiated; CD, chow diet; HFD, high-fat diet.","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-121920/v1/eecdd27ad8e0e76826386527.jpg"},{"id":4276016,"identity":"b74624df-6ae0-42f6-ae94-692b471a409c","added_by":"auto","created_at":"2020-12-15 17:15:46","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":76785,"visible":true,"origin":"","legend":"Single head-neck irradiation intervention changes the morphology of BAT cells and increases the expression of BAT Ucp-1 in HFD mice. (a): Fresh interscapular BAT gross samples. (b): The weight of BAT. (c): H\u0026E staining of BAT cells (400×). (d): The number of BAT cells from the same unit areas were counted and recorded. (e): The level of BAT Ucp-1 was measured through the western blot, with β-actin as internal control. Data are presented as means ± SEM (Ctrl+CD: n = 3; Irr+CD: n = 3; Ctrl+HFD: n =4; Irr+HFD: n = 4). *P \u003c 0.05 for the effect of irradiated mice fed an HFD vs. non-irradiated mice fed an HFD, #P \u003c 0.05 for the effect of irradiated mice fed an HFD vs. irradiated mice fed a CD, ^P \u003c 0.05 for the effect of non-irradiated mice fed an HFD vs.\nnon-irradiated mice fed a CD. Ctrl, non-irradiated; Irr, Irradiated; CD, chow diet; HFD, high-fat diet.","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-121920/v1/91754ca378c561e8190964c7.jpg"},{"id":4276017,"identity":"62731a74-a63c-4079-a1bf-cef29e6526db","added_by":"auto","created_at":"2020-12-15 17:15:46","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":63328,"visible":true,"origin":"","legend":"Effects of single head-neck irradiation on weight and morphology of WAT. (a): The weight of inguinal fat. (b): The weight of epididymal fat. (c): H\u0026E staining of WAT cells (400×). (d): The number of WAT cells from the same unit areas were counted and recorded. Data are presented as means ± SEM (a and b, Ctrl+CD: n = 4; Irr+CD: n = 6;\nCtrl+HFD: n =7; Irr+HFD: n = 8. c and d, Ctrl+CD: n = 3; Irr+CD: n = 3; Ctrl+HFD: n =3; Irr+HFD: n = 3). *P \u003c 0.05 for the effect of irradiated mice fed an HFD vs. non-irradiated mice fed an HFD, #P \u003c 0.05 for the effect of irradiated mice fed an HFD vs. non-irradiated mice fed a HFD, ^P \u003c 0.05 for the effect of non-irradiated mice fed an HFD vs. non-irradiated mice fed a CD, ^^P \u003c 0.01 for the effect of non-irradiated mice fed an HFD vs. non-irradiated mice fed a CD. Ctrl, non-irradiated; Irr, Irradiated; CD, chow diet; HFD, high-fat diet.","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-121920/v1/2d46ba84feb1f9a61f04d36c.jpg"},{"id":4276018,"identity":"b0ba8422-ce93-48ac-9493-6f6e2136985e","added_by":"auto","created_at":"2020-12-15 17:15:46","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":72677,"visible":true,"origin":"","legend":"Single head-neck irradiation intervention affects glucose tolerance and increases the expression of liver GLUT2 in HFD mice. (a): Fasting blood glucose was tested 9 weeks post irradiation. (b): IPGTT was tested 5 weeks post irradiation. (c): IPGTT was tested 9 weeks post irradiation. (d): The level of liver GLUT2 was measured through the western blot, with GAPDH as internal control. Data are presented as means ± SEM (a, b and c, Ctrl+CD: n = 4; Irr+CD: n = 6; Ctrl+HFD: n = 7; Irr+HFD: n = 8. d, Ctrl+CD: n = 3; Irr+CD: n = 4; Ctrl+HFD: n = 4; Irr+HFD: n = 4 ). *P \u003c 0.05 for the effect of irradiated mice fed an HFD vs. non-irradiated mice fed an HFD, **P \u003c 0.01 for the effect of irradiated mice fed an HFD vs. non-irradiated mice fed an HFD, #P \u003c 0.05 for the effect of irradiated mice fed an HFD vs. non-irradiated mice fed a HFD, ##P \u003c 0.01 for the effect of irradiated mice fed an HFD vs. non-irradiated mice fed a HFD, ^P \u003c 0.05 for the effect of non-irradiated mice fed an HFD vs. non-irradiated mice fed a CD, ^^P \u003c 0.01 for the\neffect of non-irradiated mice fed an HFD vs. non-irradiated mice fed a CD. Ctrl, non-irradiated; Irr, Irradiated; CD, chow diet; HFD, high-fat diet.","description":"","filename":"5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-121920/v1/db250fc28952b2c6beae0276.jpg"},{"id":4276019,"identity":"c6a7330e-099d-4468-97fe-2159fcd3e9c1","added_by":"auto","created_at":"2020-12-15 17:15:46","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":77135,"visible":true,"origin":"","legend":"Mechanisms by which single head-neck irradiation intervention affects energy metabolism. CD, chow diet; HFD, high-fat diet; (-), have no influence; (+), improve; (↓),decrease; (↑), increase; TH, thyroid hormones; T3, 3,5,3’-triiodothyronine; TR, TH receptor; SNS, sympathetic nervous system; D2, type II deiodinase; Ucp-1, uncoupling protein 1; GLUT2, Glucose transporter 2.","description":"","filename":"6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-121920/v1/f8c2c6b49ca6abda77361cf2.jpg"},{"id":4276020,"identity":"314554e9-c770-4c7e-8b62-aafb33fa2d44","added_by":"auto","created_at":"2020-12-15 17:15:47","extension":"jpg","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":67705,"visible":true,"origin":"","legend":"Schedule diagram and irradiation intervention in this study. (a): Ten-week-old C57BL/6 mice received a single dose of 6 Gy X-ray head-neck irradiation. (b): The whole experimental design. CD, chow diet; HFD, high-fat diet.","description":"","filename":"7.jpg","url":"https://assets-eu.researchsquare.com/files/rs-121920/v1/0887e6be9975c06b651972af.jpg"},{"id":13565102,"identity":"6a0b9714-7a85-4016-87e5-69f81eec8ac0","added_by":"auto","created_at":"2021-09-17 03:23:32","extension":"pdf","order_by":7,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1099484,"visible":true,"origin":"","legend":"","description":"","filename":"Manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-121920/v1_covered.pdf"},{"id":9296860,"identity":"48337bb6-991c-45b5-a43e-e1009cde80b5","added_by":"auto","created_at":"2021-05-18 12:59:22","extension":"pdf","order_by":7,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1095776,"visible":true,"origin":"","legend":"","description":"","filename":"Manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-121920/v1_covered.pdf"},{"id":4276022,"identity":"e80f7b87-095e-414f-918b-769189e5dfd0","added_by":"auto","created_at":"2020-12-15 17:15:53","extension":"pdf","order_by":7,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":726485,"visible":true,"origin":"","legend":"","description":"","filename":"Manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-121920/v1_stamped.pdf"},{"id":4276021,"identity":"e8c2e6fe-303e-4db1-a3dd-79572ab9bbe2","added_by":"auto","created_at":"2020-12-15 17:15:47","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":136670,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryInformation.pdf","url":"https://assets-eu.researchsquare.com/files/rs-121920/v1/29fe60b92d908c64ce017acc.pdf"}],"financialInterests":"","formattedTitle":"Single Head-Neck Irradiation Intervention Increases Thyroid Hormone Level and Enhances Energy Metabolism in High-Fat Diet Mice","fulltext":[{"header":"Full Text","content":"\u003cp\u003eThis preprint is available for \u003ca href='/article/rs-121920/latest.pdf' target='_blank'\u003edownload as a PDF\u003c/a\u003e.\u003c/p\u003e"}],"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":false,"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":"head-neck, irradiation, HFD, TH, energy metabolism, Ucp-1, GLUT2","lastPublishedDoi":"10.21203/rs.3.rs-121920/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-121920/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Radiotherapy, an established treatment of malignant diseases of the head and neck, increases the risk of chronic metabolic disorders. However, the molecular mechanisms responsible for metabolic dysfunction after irradiation remain unknown. We aimed to determine whether single head-neck irradiation intervention changes the levels of thyroid hormones and affects energy metabolism in high-fat diet mice and in chow diet mice. C57BL/6 mice were treated with a single dose of 6 Gy X-ray head-neck irradiation and were fed a high-fat diet. Body weight, accumulated food intake, fasting blood glucose and glucose tolerance were measured during the study. Plasma, brown adipose tissue, thyroid, liver and white adipose tissue were collected for histological analysis. We found that head-neck irradiation significantly increased food intake and decreased body weight in high-fat diet mice. However, there were no obvious changes in chow diet mice. Further studies showed that head-neck irradiation significantly increased levels of 3,5,3’-triiodothyronine and thyroid-stimulating hormone, as well as expression of uncoupling protein 1 in brown adipose tissue and glucose transporter 2 in liver in high-fat diet mice. Our results suggest that single head-neck irradiation intervention increases thyroid hormones levels and enhances energy metabolism in high-fat diet mice. 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