Mice lacking DIO3 exhibit sex-specific alterations in circadian patterns of corticosterone and gene expression in metabolic tissues
Abstract Disruption of circadian rhythms is associated with neurological, endocrine and metabolic pathologies. We have recently shown that mice lacking functional type 3 deiodinase (DIO3), the enzyme that clears thyroid hormones, exhibit a phase shift in locomotor activity, suggesting altered circad...
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| Format: | Article |
| Language: | English |
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BMC
2024-03-01
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| Series: | BMC Molecular and Cell Biology |
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| Online Access: | https://doi.org/10.1186/s12860-024-00508-6 |
| _version_ | 1797233179206090752 |
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| author | Zhaofei Wu M. Elena Martinez Arturo Hernandez |
| author_facet | Zhaofei Wu M. Elena Martinez Arturo Hernandez |
| author_sort | Zhaofei Wu |
| collection | DOAJ |
| description | Abstract Disruption of circadian rhythms is associated with neurological, endocrine and metabolic pathologies. We have recently shown that mice lacking functional type 3 deiodinase (DIO3), the enzyme that clears thyroid hormones, exhibit a phase shift in locomotor activity, suggesting altered circadian rhythm. To better understand the physiological and molecular basis of this phenotype, we used Dio3+/+ and Dio3-/- mice of both sexes at different zeitgeber times (ZTs) and analyzed corticosterone and thyroxine (T4) levels, hypothalamic, hepatic, and adipose tissue expression of clock genes, as well as genes involved in the thyroid hormone action or physiology of liver and adipose tissues. Wild type mice exhibited sexually dimorphic circadian patterns of genes controlling thyroid hormone action, including Dio3. Dio3-/- mice exhibited altered hypothalamic expression of several clock genes at ZT12, but did not disrupt the overall circadian profile. Expression of clock genes in peripheral tissues was not disrupted by Dio3 deficiency. However, Dio3 loss in liver and adipose tissues disrupted circadian profiles of genes that determine tissue thyroid hormone action and physiology. We also observed circadian-specific changes in serum T4 and corticosterone as a result of DIO3 deficiency. The circadian alterations manifested sexual dimorphism. Most notable, the time curve of serum corticosterone was flattened in Dio3-/- females. We conclude that Dio3 exhibits circadian variations, influencing the circadian rhythmicity of thyroid hormone action and physiology in liver and adipose tissues in a sex-specific manner. Circadian disruptions in tissue physiology may then contribute to the metabolic phenotypes of DIO3-deficient mice. |
| first_indexed | 2024-04-24T16:12:03Z |
| format | Article |
| id | doaj.art-582eef7136aa4200ae5cade989c331b0 |
| institution | Directory Open Access Journal |
| issn | 2661-8850 |
| language | English |
| last_indexed | 2024-04-24T16:12:03Z |
| publishDate | 2024-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Molecular and Cell Biology |
| spelling | doaj.art-582eef7136aa4200ae5cade989c331b02024-03-31T11:38:12ZengBMCBMC Molecular and Cell Biology2661-88502024-03-0125111410.1186/s12860-024-00508-6Mice lacking DIO3 exhibit sex-specific alterations in circadian patterns of corticosterone and gene expression in metabolic tissuesZhaofei Wu0M. Elena Martinez1Arturo Hernandez2MaineHealth Institute for Research, MaineHealthMaineHealth Institute for Research, MaineHealthMaineHealth Institute for Research, MaineHealthAbstract Disruption of circadian rhythms is associated with neurological, endocrine and metabolic pathologies. We have recently shown that mice lacking functional type 3 deiodinase (DIO3), the enzyme that clears thyroid hormones, exhibit a phase shift in locomotor activity, suggesting altered circadian rhythm. To better understand the physiological and molecular basis of this phenotype, we used Dio3+/+ and Dio3-/- mice of both sexes at different zeitgeber times (ZTs) and analyzed corticosterone and thyroxine (T4) levels, hypothalamic, hepatic, and adipose tissue expression of clock genes, as well as genes involved in the thyroid hormone action or physiology of liver and adipose tissues. Wild type mice exhibited sexually dimorphic circadian patterns of genes controlling thyroid hormone action, including Dio3. Dio3-/- mice exhibited altered hypothalamic expression of several clock genes at ZT12, but did not disrupt the overall circadian profile. Expression of clock genes in peripheral tissues was not disrupted by Dio3 deficiency. However, Dio3 loss in liver and adipose tissues disrupted circadian profiles of genes that determine tissue thyroid hormone action and physiology. We also observed circadian-specific changes in serum T4 and corticosterone as a result of DIO3 deficiency. The circadian alterations manifested sexual dimorphism. Most notable, the time curve of serum corticosterone was flattened in Dio3-/- females. We conclude that Dio3 exhibits circadian variations, influencing the circadian rhythmicity of thyroid hormone action and physiology in liver and adipose tissues in a sex-specific manner. Circadian disruptions in tissue physiology may then contribute to the metabolic phenotypes of DIO3-deficient mice.https://doi.org/10.1186/s12860-024-00508-6Thyroid hormone actionType 3 deiodinaseType 2 deiodinaseCircadian rhythmClock genesCorticosterone |
| spellingShingle | Zhaofei Wu M. Elena Martinez Arturo Hernandez Mice lacking DIO3 exhibit sex-specific alterations in circadian patterns of corticosterone and gene expression in metabolic tissues BMC Molecular and Cell Biology Thyroid hormone action Type 3 deiodinase Type 2 deiodinase Circadian rhythm Clock genes Corticosterone |
| title | Mice lacking DIO3 exhibit sex-specific alterations in circadian patterns of corticosterone and gene expression in metabolic tissues |
| title_full | Mice lacking DIO3 exhibit sex-specific alterations in circadian patterns of corticosterone and gene expression in metabolic tissues |
| title_fullStr | Mice lacking DIO3 exhibit sex-specific alterations in circadian patterns of corticosterone and gene expression in metabolic tissues |
| title_full_unstemmed | Mice lacking DIO3 exhibit sex-specific alterations in circadian patterns of corticosterone and gene expression in metabolic tissues |
| title_short | Mice lacking DIO3 exhibit sex-specific alterations in circadian patterns of corticosterone and gene expression in metabolic tissues |
| title_sort | mice lacking dio3 exhibit sex specific alterations in circadian patterns of corticosterone and gene expression in metabolic tissues |
| topic | Thyroid hormone action Type 3 deiodinase Type 2 deiodinase Circadian rhythm Clock genes Corticosterone |
| url | https://doi.org/10.1186/s12860-024-00508-6 |
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