{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T14:09:27Z","timestamp":1784124567986,"version":"3.55.0"},"reference-count":30,"publisher":"Bioscientifica","issue":"4","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":8,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Thyroid hormones regulate cardiovascular functions and energy homeostasis, including thermogenesis, through binding to nuclear thyroid hormone receptors. The thyroid hormone analog 3,3\u2032,5-triiodothyroacetic acid (TRIAC) has recently emerged as a therapeutic candidate for thyroid hormone transporter deficiencies (Allan\u2013Herndon\u2013Dudley syndrome) or thyroid hormone resistance \u03b2. Although TRIAC shows promise for these conditions, a comprehensive characterization focusing on heart and body temperature regulation has not been systematically performed in mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>As this knowledge is critical for determining its safety profile and therapeutic advantages over conventional thyroid hormone therapy, we administered TRIAC to wild-type mice for 14 days and assessed molecular (real-time PCR, western blot, and immunoassays) and physiological (infrared thermography and blood pressure) responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>TRIAC treatment reduced circulating thyroxine levels and induced robust upregulation of hepatic thyroid hormone-responsive genes, including Dio1 and Me1, demonstrating classical thyromimetic activity. However, cardiovascular analysis revealed normal blood pressure and heart rate, and there were no signs of cardiac hypertrophy despite specific molecular changes in cardiac gene expression. At the metabolic level, we surprisingly did not observe any effect on brown fat thermogenesis or body temperature, while in muscle, Ucp3 and Gpd2 were reduced.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Taken together, our comparative in vivo analysis demonstrates variable TRIAC responsiveness across tissues. Under defined conditions, the drug produces defined metabolic responses while avoiding classical hyperthyroid manifestations, such as tachycardia or hyperthermia, thus supporting its potential therapeutic use in thyroid hormone resistance conditions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1530\/etj-26-0102","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T16:11:26Z","timestamp":1782317486000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-17","source":"Crossref","is-referenced-by-count":0,"title":["Triiodothyroacetic acid exerts tissue-specific thyromimetic effects without tachycardia and hyperthermia in male mice"],"prefix":"10.1530","volume":"15","author":[{"given":"Beate","family":"Herrmann","sequence":"first","affiliation":[{"name":"Institute for Experimental Endocrinology, CBBM, University of Luebeck\/UKSH 1 , ,","place":["Luebeck, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Adam","sequence":"additional","affiliation":[{"name":"Institute for Experimental Endocrinology, CBBM, University of Luebeck\/UKSH 1 , ,","place":["Luebeck, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Oelkrug","sequence":"additional","affiliation":[{"name":"Institute for Experimental Endocrinology, CBBM, University of Luebeck\/UKSH 1 , ,","place":["Luebeck, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7778-5158","authenticated-orcid":true,"given":"Jens","family":"Mittag","sequence":"additional","affiliation":[{"name":"Institute for Experimental Endocrinology, CBBM, University of Luebeck\/UKSH 1 , ,","place":["Luebeck, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"2026071509264415100_bib1","doi-asserted-by":"crossref","DOI":"10.1210\/endocr\/bqae093","article-title":"Thyroid hormone receptors in control of heart rate","volume":"165","author":"Dore","year":"2024","journal-title":"Endocrinology"},{"key":"2026071509264415100_bib2","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1152\/physrev.2001.81.3.1097","article-title":"Physiological and molecular basis of thyroid hormone action","volume":"81","author":"Yen","year":"2001","journal-title":"Physiol Rev"},{"key":"2026071509264415100_bib3","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1210\/en.2004-1179","article-title":"The monocarboxylate transporter 8 linked to human psychomotor retardation is highly expressed in thyroid hormone-sensitive neuron populations","volume":"146","author":"Heuer","year":"2005","journal-title":"Endocrinology"},{"key":"2026071509264415100_bib4","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1016\/S2213-8587(20)30153-4","article-title":"Disease characteristics of MCT8 deficiency: an international, retrospective, multicentre cohort study","volume":"8","author":"Groeneweg","year":"2020","journal-title":"Lancet Diabetes Endocrinol"},{"key":"2026071509264415100_bib5","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1172\/JCI28253","article-title":"Abnormal thyroid hormone metabolism in mice lacking the monocarboxylate transporter 8","volume":"117","author":"Trajkovic","year":"2007","journal-title":"J Clin Investig"},{"key":"2026071509264415100_bib6","doi-asserted-by":"crossref","first-page":"1987","DOI":"10.1172\/JCI70324","article-title":"Transporters MCT8 and OATP1C1 maintain murine brain thyroid hormone homeostasis","volume":"124","author":"Mayerl","year":"2014","journal-title":"J Clin Investig"},{"key":"2026071509264415100_bib7","doi-asserted-by":"crossref","first-page":"3452","DOI":"10.3390\/ijms24043452","article-title":"Triac treatment prevents neurodevelopmental and locomotor impairments in thyroid hormone transporter Mct8\/Oatp1c1 deficient mice","volume":"24","author":"Chen","year":"2023","journal-title":"Int J Mol Sci"},{"key":"2026071509264415100_bib8","doi-asserted-by":"crossref","DOI":"10.1530\/ETJ-24-0286","article-title":"Toward a treatment for thyroid hormone transporter MCT8 deficiency \u2013 achievements and challenges","volume":"13","author":"Markova","year":"2024","journal-title":"Eur Thyroid J"},{"key":"2026071509264415100_bib9","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1089\/thy.2025.0245","article-title":"Thyroid hormone analogs: recent developments","volume":"35","author":"Freund","year":"2025","journal-title":"Thyroid"},{"key":"2026071509264415100_bib10","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1210\/me.2014-1135","article-title":"In vitro and mouse studies supporting therapeutic utility of triiodothyroacetic acid in MCT8 deficiency","volume":"28","author":"Kersseboom","year":"2014","journal-title":"Mol Endocrinol"},{"key":"2026071509264415100_bib11","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1210\/clinem\/dgaf583","article-title":"TRIAC therapy relieves hyperthyroid symptoms, lowering T4, T3, and metabolic rate in resistance to thyroid hormone beta","volume":"111","author":"Moran","year":"2026","journal-title":"J Clin Endocrinol Metab"},{"key":"2026071509264415100_bib12","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/j.tem.2021.05.006","article-title":"Thyroid wars: the rise of central actions","volume":"32","author":"Capelli","year":"2021","journal-title":"Trends Endocrinol Metab"},{"key":"2026071509264415100_bib13","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1007\/s11154-025-09966-5","article-title":"Hypothalamic control of heart rate and body temperature by thyroid hormones","volume":"27","author":"Mittag","year":"2025","journal-title":"Rev Endocr Metab Disord"},{"key":"2026071509264415100_bib14","doi-asserted-by":"crossref","DOI":"10.1016\/j.isci.2023.108064","article-title":"Lack of thyroid hormone receptor beta is not detrimental for non-alcoholic steatohepatitis progression","volume":"26","author":"Lopez-Alcantara","year":"2023","journal-title":"iScience"},{"key":"2026071509264415100_bib15","doi-asserted-by":"crossref","first-page":"2940","DOI":"10.1210\/en.2008-1085","article-title":"Interference of a mutant thyroid hormone receptor alpha1 with hepatic glucose metabolism","volume":"150","author":"Vujovic","year":"2009","journal-title":"Endocrinology"},{"key":"2026071509264415100_bib16","doi-asserted-by":"crossref","first-page":"3312","DOI":"10.1038\/s41467-023-38960-1","article-title":"Resistance to thyroid hormone induced tachycardia in RTHalpha syndrome","volume":"14","author":"Dore","year":"2023","journal-title":"Nat Commun"},{"key":"2026071509264415100_bib17","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1089\/thy.2019.0705","article-title":"Central hypothyroidism impairs heart rate stability and prevents thyroid hormone-induced cardiac hypertrophy and pyrexia","volume":"30","author":"Herrmann","year":"2020","journal-title":"Thyroid"},{"key":"2026071509264415100_bib18","doi-asserted-by":"crossref","first-page":"6742","DOI":"10.1038\/s41467-023-42425-w","article-title":"Maternal thyroid hormone receptor beta activation in mice sparks brown fat thermogenesis in the offspring","volume":"14","author":"Oelkrug","year":"2023","journal-title":"Nat Commun"},{"key":"2026071509264415100_bib19","doi-asserted-by":"crossref","first-page":"4799","DOI":"10.1038\/s41598-021-84200-1","article-title":"An improved method for the precise unravelment of non-shivering brown fat thermokinetics","volume":"11","author":"Oelkrug","year":"2021","journal-title":"Sci Rep"},{"key":"2026071509264415100_bib20","doi-asserted-by":"crossref","first-page":"R99","DOI":"10.1530\/JOE-17-0113","article-title":"Triiodothyroacetic acid in health and disease","volume":"234","author":"Groeneweg","year":"2017","journal-title":"J Endocrinol"},{"key":"2026071509264415100_bib21","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1210\/endo-98-3-666","article-title":"Comparison of the metabolism and distribution of L-triiodothyronine and triiodothyroacetic acid in the rat: a possible explanation of differential hormonal potency","volume":"98","author":"Goslings","year":"1976","journal-title":"Endocrinology"},{"key":"2026071509264415100_bib22","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1089\/thy.2015.0388","article-title":"Effect of triiodothyroacetic acid treatment in Mct8 deficiency: a word of caution","volume":"26","author":"Barez-Lopez","year":"2016","journal-title":"Thyroid"},{"key":"2026071509264415100_bib23","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1089\/thy.2023.0513","article-title":"Hypothalamic thyroid hormone receptor alpha1 signaling controls body temperature","volume":"34","author":"Sentis","year":"2024","journal-title":"Thyroid"},{"key":"2026071509264415100_bib24","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1089\/thy.2023.0467","article-title":"3,3\u2032,5-Triiodothyroacetic acid transporters","volume":"34","author":"Chen","year":"2024","journal-title":"Thyroid"},{"key":"2026071509264415100_bib25","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/S0300-9084(99)80095-9","article-title":"Tissue-specific patterns of changes in 3,5,3\u2032-triiodo-L-thyronine concentrations in thyroidectomized rats infused with increasing doses of the hormone. Which are the regulatory mechanisms?","volume":"81","author":"Escobar-Morreale","year":"1999","journal-title":"Biochimie"},{"key":"2026071509264415100_bib26","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0226017","article-title":"Intracerebroventricular administration of the thyroid hormone analog TRIAC increases its brain content in the absence of MCT8","volume":"14","author":"Barez-Lopez","year":"2019","journal-title":"PLoS One"},{"key":"2026071509264415100_bib27","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1089\/thy.2022.0562","article-title":"Intracerebroventricular high doses of 3,3\u2032,5-triiodothyroacetic acid at juvenile stages improve peripheral hyperthyroidism and mediate thyromimetic effects in limited brain regions in a mouse model of monocarboxylate transporter 8 deficiency","volume":"33","author":"Grijota-Martinez","year":"2023","journal-title":"Thyroid"},{"key":"2026071509264415100_bib28","doi-asserted-by":"crossref","first-page":"3385","DOI":"10.1016\/j.celrep.2019.05.054","article-title":"Thyroid-hormone-induced browning of white adipose tissue does not contribute to thermogenesis and glucose consumption","volume":"27","author":"Johann","year":"2019","journal-title":"Cell Rep"},{"key":"2026071509264415100_bib29","doi-asserted-by":"crossref","first-page":"R106","DOI":"10.1530\/EC-20-0562","article-title":"Thyroid hormones in the regulation of brown adipose tissue thermogenesis","volume":"10","author":"Sentis","year":"2021","journal-title":"Endocr Connect"},{"key":"2026071509264415100_bib30","doi-asserted-by":"crossref","first-page":"2957","DOI":"10.1210\/en.2016-1095","article-title":"Thermoregulatory and cardiovascular consequences of a transient thyrotoxicosis and recovery in male mice","volume":"157","author":"Hoefig","year":"2016","journal-title":"Endocrinology"}],"container-title":["European Thyroid Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/etj.bioscientifica.com\/view\/journals\/etj\/aop\/ETJ-26-0102\/ETJ-26-0102.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/etj.bioscientifica.com\/downloadpdf\/journals\/etj\/aop\/ETJ-26-0102\/ETJ-26-0102.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.bioscientifica.com\/etj\/article-pdf\/doi\/10.1530\/ETJ-26-0102\/519730\/etj-26-0102.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.bioscientifica.com\/etj\/article-pdf\/doi\/10.1530\/ETJ-26-0102\/519730\/etj-26-0102.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T13:26:52Z","timestamp":1784122012000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.bioscientifica.com\/etj\/article\/15\/4\/ETJ260102\/77529\/Triiodothyroacetic-acid-exerts-tissue-specific"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,24]]},"references-count":30,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,8,1]]}},"URL":"https:\/\/doi.org\/10.1530\/etj-26-0102","relation":{},"ISSN":["2235-0802"],"issn-type":[{"value":"2235-0802","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,24]]},"article-number":"ETJ260102"}}