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Leptin counteracts hypothermia in hypothyroidism through its pyrexic effects and by stabilizing serum thyroid hormone levels.
Mol. Metab. 54:101348 (2021)
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 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. Thermogenic and metabolic effects were analyzed through metabolic chambers, 18F-FDG-PET/MRI, infrared thermography, metabolic profiling, histology, gene expression and Wester 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 a 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 confers a stimulatory effect on the HPT axis to stabilize 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.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Beige Adipose Tissue ; Brown Adipose Tissue ; Leptin ; Thermogenesis ; Thyroid Hormone ; White Adipose Tissue Browning; Brown Adipose-tissue; Body-temperature; Heat Dissipation; Cold-exposure; Trh Neurons; Thermogenesis; White; Pituitary; Receptors; Mice
ISSN (print) / ISBN
2212-8778
e-ISSN
2212-8778
Zeitschrift
Molecular Metabolism
Quellenangaben
Band: 54,
Artikelnummer: 101348
Verlag
Elsevier
Verlagsort
Amsterdam
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
Institute of Diabetes and Obesity (IDO)
Institute of Diabetes and Obesity (IDO)
Förderungen
Helmholtz Zentrum Munchen
Medical Faculty of the University Leipzig
Deutsche Forschungsgemeinschaft
Medical Faculty of the University Leipzig
Deutsche Forschungsgemeinschaft