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Leptin counteracts hypothermia in hypothyroidism through its pyrexic effects and by stabilizing serum thyroid hormone levels
OBJECTIVE: Thyroid hormones (TH) are essential for the homeostatic control of energy metabolism and the regulation of body temperature. The hypothalamic–pituitary–thyroid (HPT) axis is regulated by negative feedback mechanisms, ensuring that TH levels are maintained at a constant level. However, the...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8556519/ https://www.ncbi.nlm.nih.gov/pubmed/34610354 http://dx.doi.org/10.1016/j.molmet.2021.101348 |
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author | Weiner, Juliane Roth, Lisa Kranz, Mathias Brust, Peter Boelen, Anita Klöting, Nora Heiker, John T. Blüher, Matthias Tönjes, Anke Pfluger, Paul T. Stumvoll, Michael Mittag, Jens Krause, Kerstin |
author_facet | Weiner, Juliane Roth, Lisa Kranz, Mathias Brust, Peter Boelen, Anita Klöting, Nora Heiker, John T. Blüher, Matthias Tönjes, Anke Pfluger, Paul T. Stumvoll, Michael Mittag, Jens Krause, Kerstin |
author_sort | Weiner, Juliane |
collection | PubMed |
description | OBJECTIVE: Thyroid hormones (TH) are essential for the homeostatic control of energy metabolism and the regulation of body temperature. The hypothalamic–pituitary–thyroid (HPT) axis is regulated by negative feedback mechanisms, ensuring that TH levels are maintained at a constant level. However, the feedback mechanisms underlying the resetting of the HPT axis regulation in the control of body temperature are still not fully understood. Here, we aimed to determine the thermoregulatory response in hypothyroid mice to different environmental temperatures and the underlying mechanisms. METHODS: Distinct thermogenic challenges were induced in hypothyroid female C57BL/6N and leptin-deficient ob/ob mice through housing at either room temperature or thermoneutrality. The thermogenic and metabolic effects were analyzed through metabolic chambers, 18F-FDG-PET/MRI, infrared thermography, metabolic profiling, histology, gene expression and Western blot analysis. RESULTS: In hypothyroid mice maintained at room temperature, high leptin serum levels induce a pyrexic effect leading to the stabilization of body temperature through brown adipose tissue thermogenesis and white adipose tissue browning. Housing at thermoneutrality leads to the normalization of leptin levels and a reduction of the central temperature set point, resulting in decreased thermogenesis in brown and white adipose tissue and skeletal muscle and a significant decline in body temperature. Furthermore, anapyrexia in hypothyroid leptin-deficient ob/ob mice indicates that besides its pyrexic actions, leptin exerts a stimulatory effect on the HPT axis to stabilize the remaining TH serum levels in hypothyroid mice. CONCLUSION: This study led to the identification of a previously unknown endocrine loop in which leptin acts in concert with the HPT axis to stabilize body temperature in hypothyroid mice. |
format | Online Article Text |
id | pubmed-8556519 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-85565192021-11-05 Leptin counteracts hypothermia in hypothyroidism through its pyrexic effects and by stabilizing serum thyroid hormone levels Weiner, Juliane Roth, Lisa Kranz, Mathias Brust, Peter Boelen, Anita Klöting, Nora Heiker, John T. Blüher, Matthias Tönjes, Anke Pfluger, Paul T. Stumvoll, Michael Mittag, Jens Krause, Kerstin Mol Metab Original Article OBJECTIVE: Thyroid hormones (TH) are essential for the homeostatic control of energy metabolism and the regulation of body temperature. The hypothalamic–pituitary–thyroid (HPT) axis is regulated by negative feedback mechanisms, ensuring that TH levels are maintained at a constant level. However, the feedback mechanisms underlying the resetting of the HPT axis regulation in the control of body temperature are still not fully understood. Here, we aimed to determine the thermoregulatory response in hypothyroid mice to different environmental temperatures and the underlying mechanisms. METHODS: Distinct thermogenic challenges were induced in hypothyroid female C57BL/6N and leptin-deficient ob/ob mice through housing at either room temperature or thermoneutrality. The thermogenic and metabolic effects were analyzed through metabolic chambers, 18F-FDG-PET/MRI, infrared thermography, metabolic profiling, histology, gene expression and Western blot analysis. RESULTS: In hypothyroid mice maintained at room temperature, high leptin serum levels induce a pyrexic effect leading to the stabilization of body temperature through brown adipose tissue thermogenesis and white adipose tissue browning. Housing at thermoneutrality leads to the normalization of leptin levels and a reduction of the central temperature set point, resulting in decreased thermogenesis in brown and white adipose tissue and skeletal muscle and a significant decline in body temperature. Furthermore, anapyrexia in hypothyroid leptin-deficient ob/ob mice indicates that besides its pyrexic actions, leptin exerts a stimulatory effect on the HPT axis to stabilize the remaining TH serum levels in hypothyroid mice. CONCLUSION: This study led to the identification of a previously unknown endocrine loop in which leptin acts in concert with the HPT axis to stabilize body temperature in hypothyroid mice. Elsevier 2021-10-02 /pmc/articles/PMC8556519/ /pubmed/34610354 http://dx.doi.org/10.1016/j.molmet.2021.101348 Text en © 2021 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Article Weiner, Juliane Roth, Lisa Kranz, Mathias Brust, Peter Boelen, Anita Klöting, Nora Heiker, John T. Blüher, Matthias Tönjes, Anke Pfluger, Paul T. Stumvoll, Michael Mittag, Jens Krause, Kerstin Leptin counteracts hypothermia in hypothyroidism through its pyrexic effects and by stabilizing serum thyroid hormone levels |
title | Leptin counteracts hypothermia in hypothyroidism through its pyrexic effects and by stabilizing serum thyroid hormone levels |
title_full | Leptin counteracts hypothermia in hypothyroidism through its pyrexic effects and by stabilizing serum thyroid hormone levels |
title_fullStr | Leptin counteracts hypothermia in hypothyroidism through its pyrexic effects and by stabilizing serum thyroid hormone levels |
title_full_unstemmed | Leptin counteracts hypothermia in hypothyroidism through its pyrexic effects and by stabilizing serum thyroid hormone levels |
title_short | Leptin counteracts hypothermia in hypothyroidism through its pyrexic effects and by stabilizing serum thyroid hormone levels |
title_sort | leptin counteracts hypothermia in hypothyroidism through its pyrexic effects and by stabilizing serum thyroid hormone levels |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8556519/ https://www.ncbi.nlm.nih.gov/pubmed/34610354 http://dx.doi.org/10.1016/j.molmet.2021.101348 |
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