{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T03:07:23Z","timestamp":1790996843240,"version":"4.1.0"},"reference-count":41,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2020,7,1]],"date-time":"2020-07-01T00:00:00Z","timestamp":1593561600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Thyroid\u00ae"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Sepsis can cause the nonthyroidal illness syndrome (NTIS), resulting in perturbed thyroid hormone (TH) signaling and reduced thyroxine (T4) levels. TH is a major regulator of muscle function, via its influence on mitochondria. This study aimed at evaluating the relationship between TH signaling, mitochondrial function, and the antioxidant defense system in the diaphragms of septic mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Male C57Bl\/6 mice were divided into two groups: cecal ligation and puncture (CLP) and sham. Twenty-four hours after surgery, plasma, diaphragms, and livers were collected. TH metabolism and responses were analyzed by measuring messenger RNA (mRNA) expression of\n                      <jats:italic toggle=\"yes\">Dio1<\/jats:italic>\n                      in the liver, and\n                      <jats:italic toggle=\"yes\">Thra<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Thrb<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Dio<\/jats:italic>\n                      2,\n                      <jats:italic toggle=\"yes\">Slc16a10<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">Slc16a2<\/jats:italic>\n                      (encodes MCT 10 and 8), in the diaphragm. T4 plasma levels were measured by radioimmunoassay. Damage to diaphragm mitochondria was assessed by electron microscopy and real-time polymerase chain reaction (qPCR), and function with oxygraphy. The diaphragm antioxidative defense system was examined by qPCR, analyzing superoxide dismutase (SOD) 1 (\n                      <jats:italic toggle=\"yes\">Sod1<\/jats:italic>\n                      ), mitochondrial superoxide dismutase (SOD 2;\n                      <jats:italic toggle=\"yes\">Sod2<\/jats:italic>\n                      ), extracellular superoxide dismutase (SOD 3;\n                      <jats:italic toggle=\"yes\">Sod3<\/jats:italic>\n                      ), glutathione peroxidase 1 (\n                      <jats:italic toggle=\"yes\">Gpx1<\/jats:italic>\n                      ), and catalase (\n                      <jats:italic toggle=\"yes\">Cat<\/jats:italic>\n                      ) expression. The effect of TH replacement was tested by treating the mice with T4 and triiodothyronine (T3) (CLP+TH) after surgery.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      CLP mice presented reduced total plasma T4 concentrations, downregulated\n                      <jats:italic toggle=\"yes\">Dio1<\/jats:italic>\n                      , and upregulated\n                      <jats:italic toggle=\"yes\">Il1b<\/jats:italic>\n                      mRNA expression in the liver. CLP mice also displayed downregulated\n                      <jats:italic toggle=\"yes\">Thra, Thrb, Slc16a10<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">Slc16a2<\/jats:italic>\n                      expression in the diaphragm, suggesting that TH signaling was compromised. The expression of\n                      <jats:italic toggle=\"yes\">Ppargc1a<\/jats:italic>\n                      (encoding PGC1a) was downregulated, which correlated with the decrease in the number of total mitochondria, increase in the percentage of injured mitochondria, downregulation of respiratory chain complex 2 and 3 mRNA expression, and reduced maximal respiration. In addition, septic animals presented a three-fold increase in\n                      <jats:italic toggle=\"yes\">Ucp3<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">G6pdh<\/jats:italic>\n                      expression; downregulated\n                      <jats:italic toggle=\"yes\">Sod3<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Gpx1<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">Cat<\/jats:italic>\n                      expression; and upregulated\n                      <jats:italic toggle=\"yes\">Sod2<\/jats:italic>\n                      expression, potentially due to elevated reactive oxygen species levels. The mitochondrial number and the percentage of injured mitochondrial were similar between sham and CLP+TH mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Sepsis induced responses consistent with NTIS, resulted in mitochondrial damage and functional impairment, and modulated the expression of key antioxidant enzymes in the diaphragm. Thus, impaired diaphragm function during sepsis seems to involve altered local TH signaling, mitochondrial dysfunction, and oxidative stress defense.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/thy.2019.0124","type":"journal-article","created":{"date-parts":[[2020,3,21]],"date-time":"2020-03-21T03:05:37Z","timestamp":1584759937000},"page":"1079-1090","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":26,"title":["Sepsis Impairs Thyroid Hormone Signaling and Mitochondrial Function in the Mouse Diaphragm"],"prefix":"10.1177","volume":"30","author":[{"given":"Flavia Fonseca","family":"Bloise","sequence":"first","affiliation":[{"name":"Laboratory of Translational Endocrinology, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anderson Teixeira","family":"Santos","sequence":"additional","affiliation":[{"name":"Laboratory of Metabolic Adaptations, Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana","family":"de Brito","sequence":"additional","affiliation":[{"name":"Laboratory of Translational Endocrinology, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cherley Borba Vieira","family":"de Andrade","sequence":"additional","affiliation":[{"name":"Laboratory of Translational Endocrinology, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thamires Siqueira","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Laboratory of Translational Endocrinology, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aline Fonseca Pereira","family":"de Souza","sequence":"additional","affiliation":[{"name":"Laboratory of Translational Endocrinology, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus Novaes","family":"Fontes","sequence":"additional","affiliation":[{"name":"Laboratory of Translational Endocrinology, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johnatas D","family":"Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nat\u00e1lia","family":"Blanco","sequence":"additional","affiliation":[{"name":"Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro Leme","family":"Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia Rieken Macedo","family":"Rocco","sequence":"additional","affiliation":[{"name":"Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Fliers","sequence":"additional","affiliation":[{"name":"Department of Endocrinology &amp; 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