Maternal thyroid hormone receptor β activation in mice sparks brown fat thermogenesis in the offspring

Rebecca Oelkrug; Lisbeth Harder; Mehdi Pedaran; Anne Hoffmann; Beke Kolms; Julica Inderhees; Sogol Gachkar; Julia Resch; Kornelia Johann; Olaf Jöhren; Kerstin Krause; Jens Mittag

doi:10.1038/s41467-023-42425-w

Maternal thyroid hormone receptor β activation in mice sparks brown fat thermogenesis in the offspring

Rebecca Oelkrug, Lisbeth Harder, Mehdi Pedaran, Anne Hoffmann, Beke Kolms, Julica Inderhees, Sogol Gachkar, Julia Resch, Kornelia Johann, Olaf Jöhren, Kerstin Krause, Jens Mittag^*

^*Korrespondierende/r Autor/-in für diese Arbeit

Universität Leipzig

Abstract

It is well established that maternal thyroid hormones play an important role for the developing fetus; however, the consequences of maternal hyperthyroidism for the offspring remain poorly understood. Here we show in mice that maternal 3,3’,5-triiodothyronine (T3) treatment during pregnancy leads to improved glucose tolerance in the adult male offspring and hyperactivity of brown adipose tissue (BAT) thermogenesis in both sexes starting early after birth. The activated BAT provides advantages upon cold exposure, reducing the strain on other thermogenic organs like muscle. This maternal BAT programming requires intact maternal thyroid hormone receptor β (TRβ) signaling, as offspring of mothers lacking this receptor display the opposite phenotype. On the molecular level, we identify distinct T3 induced alterations in maternal serum metabolites, including choline, a key metabolite for healthy pregnancy. Taken together, our results connect maternal TRβ activation to the fetal programming of a thermoregulatory phenotype in the offspring.

Originalsprache	Englisch
Aufsatznummer	6742
Zeitschrift	Nature Communications
Jahrgang	14
Ausgabenummer	1
Seiten (von - bis)	6742
ISSN	1751-8628
DOIs	https://doi.org/10.1038/s41467-023-42425-w
Publikationsstatus	Veröffentlicht - 12.2023

Strategische Forschungsbereiche und Zentren

Forschungsschwerpunkt: Gehirn, Hormone, Verhalten - Center for Brain, Behavior and Metabolism (CBBM)

DFG-Fachsystematik

205-17 Endokrinologie, Diabetologie, Metabolismus

UN SDGs

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10.1038/s41467-023-42425-w

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SFB/Transregio TRR 296 LocoTact: Lokale Kontrolle der Schilddrüsenhormonwirkung
Führer-Sakel, D., Mittag, J., Kühnen, P., Heuer, H., Schwaninger, M., Müller-Fielitz, H., Bechmann, I., Biebermann, H., Müller, T., Pfluger, P., Krude, H., Schülke-Gerstenfeld, M., Cirkel, A., Münte, T., Kleinschnitz, C., Langhauser, F., Engel, D. R., Möller, L., Kaiser, F., Oster, H., Kirchner, H., Spranger, J., Tacke, F., Wirth, E. K., Köhrle, J., Schomburg, L., Lange, C. M., Zwanziger, D., Mayerl, S. & Stachelscheid, H.
01.01.20 → …
Projekt: DFG-Projekte › DFG-Verbundforschung: Sonderforschungsbereiche/ Transregios

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title = "Maternal thyroid hormone receptor β activation in mice sparks brown fat thermogenesis in the offspring",

abstract = "It is well established that maternal thyroid hormones play an important role for the developing fetus; however, the consequences of maternal hyperthyroidism for the offspring remain poorly understood. Here we show in mice that maternal 3,3{\textquoteright},5-triiodothyronine (T3) treatment during pregnancy leads to improved glucose tolerance in the adult male offspring and hyperactivity of brown adipose tissue (BAT) thermogenesis in both sexes starting early after birth. The activated BAT provides advantages upon cold exposure, reducing the strain on other thermogenic organs like muscle. This maternal BAT programming requires intact maternal thyroid hormone receptor β (TRβ) signaling, as offspring of mothers lacking this receptor display the opposite phenotype. On the molecular level, we identify distinct T3 induced alterations in maternal serum metabolites, including choline, a key metabolite for healthy pregnancy. Taken together, our results connect maternal TRβ activation to the fetal programming of a thermoregulatory phenotype in the offspring.",

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AU - Kolms, Beke

AU - Inderhees, Julica

AU - Gachkar, Sogol

AU - Resch, Julia

AU - Johann, Kornelia

AU - Jöhren, Olaf

AU - Krause, Kerstin

AU - Mittag, Jens

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Maternal thyroid hormone receptor β activation in mice sparks brown fat thermogenesis in the offspring

Abstract

Strategische Forschungsbereiche und Zentren

DFG-Fachsystematik

UN SDGs

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Projekte

SFB/Transregio TRR 296 LocoTact: Lokale Kontrolle der Schilddrüsenhormonwirkung

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