{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T11:21:48Z","timestamp":1788952908022,"version":"build-2803163510"},"reference-count":60,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2024,9,15]],"date-time":"2024-09-15T00:00:00Z","timestamp":1726358400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2024,9,15]],"date-time":"2024-09-15T00:00:00Z","timestamp":1726358400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      In mammals, the central circadian oscillator is located in the suprachiasmatic nucleus (SCN). Hypothalamus\u2013pituitary\u2013thyroid axis components exhibit circadian oscillation, regulated by both central clock innervation and intrinsic circadian clocks in the anterior pituitary and thyroid glands. Thyroid disorders alter the rhythmicity of peripheral clocks in a tissue\u2010dependent response; however, whether these effects are influenced by alterations in the master clock remains unknown. This study aimed to characterize the effects of hypothyroidism on the rhythmicity of SCN, body temperature (BT) and metabolism, and the possible mechanisms involved in this signalling. C57BL\/6J adult male mice were divided into Control and Hypothyroid groups. Profiles of spontaneous locomotor activity (SLA), BT, oxygen consumption () and respiratory quotient (RQ) were determined under free\u2010running conditions. Clock gene expression, and neuronal activity of the SCN and medial preoptic nucleus (MPOM) area were investigated in light\u2013dark (LD) conditions. Triiodothyronine (T3) transcriptional regulation of\n                      <jats:italic>Bmal1<\/jats:italic>\n                      promoter activity was evaluated in GH3\u2010transfected cells. Hypothyroidism delayed the rhythmicity of SLA and BT, and altered the expression of core clock components in the SCN. The activity of SCN neurons and their outputs were also affected, as evidenced by the loss of circadian rhythmicity in  and RQ and alterations in the neuronal activity pattern of MPOM. In GH3 cells, T3 increased\n                      <jats:italic>Bmal1<\/jats:italic>\n                      promoter activity in a time\u2010dependent manner. Thyroid hormone may act as a temporal cue for the central circadian clock, and the uncoupling of central and peripheral clocks might contribute to a wide range of metabolic and thermoregulatory impairments observed in hypothyroidism.\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp16317-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Hypothyroidism alters clock gene expression in the suprachiasmatic nucleus (SCN).<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Thyroid hypofunction alters the phase of spontaneous locomotor activity and body temperature rhythms.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Thyroid hormone deficiency alters the daily pattern of SCN and medial preoptic nucleus neuronal activities.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Hypothyroidism alterations are extended to daily oscillations of oxygen consumption and metabolism, which might contribute to the development of metabolic syndrome.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Triiodothyronine increases\n                            <jats:italic>Bmal1<\/jats:italic>\n                            promoter activity acting as temporal cue for the central circadian clock.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp286449","type":"journal-article","created":{"date-parts":[[2024,9,15]],"date-time":"2024-09-15T10:23:31Z","timestamp":1726395811000},"page":"4865-4887","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Hypothyroidism alters the rhythmicity of the central clock, body temperature and metabolism: evidence of\n                    <i>Bmal1<\/i>\n                    transcriptional regulation by T3"],"prefix":"10.1113","volume":"602","author":[{"given":"Felipe","family":"Emrich","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biological Sciences Federal University of Minas Gerais  Belo Horizonte MG Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno Henrique","family":"Gomes","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biological Sciences Federal University of Minas Gerais  Belo Horizonte MG Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Let\u00edcia","family":"Selvatici\u2010Tolentino","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biological Sciences Federal University of Minas Gerais  Belo Horizonte MG Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta 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Institute of Biological Sciences Federal University of Minas Gerais  Belo Horizonte MG Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2566-2532","authenticated-orcid":false,"given":"Leonardo de Oliveira","family":"Guarnieri","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biological Sciences Federal University of Minas Gerais  Belo Horizonte MG Brazil"},{"name":"Department of Electrical Engineering, Engineering School Federal University of Minas Gerais (UFMG)  Belo Horizonte MG Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana B\u00e1rbara de Paula","family":"Silva","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biological Sciences Federal University of Minas Gerais  Belo Horizonte MG Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas 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