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

Author

Listed:
  • Rebecca Oelkrug

    (University of Lübeck)

  • Lisbeth Harder

    (University of Lübeck)

  • Mehdi Pedaran

    (University of Lübeck)

  • Anne Hoffmann

    (Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig and University Hospital Leipzig)

  • Beke Kolms

    (University of Lübeck)

  • Julica Inderhees

    (University of Lübeck)

  • Sogol Gachkar

    (University of Lübeck)

  • Julia Resch

    (University of Lübeck)

  • Kornelia Johann

    (University of Lübeck)

  • Olaf Jöhren

    (University of Lübeck)

  • Kerstin Krause

    (University of Leipzig Medical Center)

  • Jens Mittag

    (University of Lübeck)

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.

Suggested Citation

  • Rebecca Oelkrug & Lisbeth Harder & Mehdi Pedaran & Anne Hoffmann & Beke Kolms & Julica Inderhees & Sogol Gachkar & Julia Resch & Kornelia Johann & Olaf Jöhren & Kerstin Krause & Jens Mittag, 2023. "Maternal thyroid hormone receptor β activation in mice sparks brown fat thermogenesis in the offspring," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42425-w
    DOI: 10.1038/s41467-023-42425-w
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    1. Adela Urisarri & Ismael González-García & Ánxela Estévez-Salguero & María P. Pata & Edward Milbank & Noemi López & Natalia Mandiá & Carmen Grijota-Martinez & Carlos A. Salgado & Rubén Nogueiras & Carl, 2021. "BMP8 and activated brown adipose tissue in human newborns," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
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