Interaction of thyroid hormone with brown adipose tissue

Summary

Brown adipose tissue (BAT) plays an important role in regulating core-body temperature in various species including man. [¹⁸F]FDGPET/ CT imaging first revealed the presence of metabolically active BAT depots and that decreased BAT function is associated with various metabolic conditions. Thyroid hormone (TH) in concert with sympathetic nervous system signalling (SNS) stimulates BAT thermogenesis and thyroid disorders result in dysfunctional BAT. Currently, research is focussing not only on BAT regulation but also on browning of white adipose tissue (WAT) to BAT beige adipose tissue (BeAT) in order to develop novel treatments for human obesity and related conditions. While [¹⁸F]FDG-PET/ CT imaging is continuing to provide valuable insights into BAT and BeAT function in health and disease, there is a pressing need to develop alternative radiotracers that reliably track their activity in vivo. As a result it is expected that preclinical micro PET/CT investigations of BAT and BeAT will gain in prominence.

The aim of this short review is to i) describe fundamentals in BAT biology, ii) highlight some of the clinical and preclinical studies performed on humans and rodents with a focus on TH, BAT and PET/CT, and iii) bridge these data with our own studies within the DFG thyroid transact priority program.

Zusammenfassung

Braunes Fettgewebe (BAT) besitzt in der Regulation von Körpertemperatur und Energiebalance eine zentrale Rolle. Durch [¹⁸F]FDG-PET/ CT gelang der Nachweis von metabolisch aktivem BAT bei Erwachsenen, wobei sich im Folgenden zeigte, dass eine verminderte BAT-Aktivität mit verschiedenen metabolischen Veränderungen assoziiert ist. Schilddrüsenhormone (TH) aktivieren BAT gemeinsam mit dem sympathischen Nervensystem, sodass auch Schilddrüsenerkrankungen mit einer BAT-Fehlfunktion einhergehen können und es werden zudem ständig weitere BAT-stimulierende Faktoren identifiziert. Der wissenschaftliche Fokus hat sich im vergangenen Jahrzehnt nicht nur auf das Verständnis der BAT-Regulation gerichtet, sondern auch auf eine Transdifferenzierung von weißem Fettgewebe (WAT) zu beigem Fettgewebe (BeAT), um somit neue Behandlungsoptionen für Adipositas und Adipositas-assoziierte Erkrankungen zu gewinnen. [¹⁸F]FDG-PET/CT ermöglicht hierbei einen Einblick in den BATStoffwechsel, auch wenn weiterhin noch Bedarf an alternativen Tracern besteht, die die BAT- und BeAT-Aktivität in vivo nachweisen können. Infolge dessen wird erwartet, dass präklinische PET/CT-Untersuchungen im Hinblick auf BAT- und BeAT-Funktion an Bedeutung gewinnen.

Wir möchten in dieser übersichtsarbeit i) Einblick in die BAT-Biologie geben, ii) bisherige klinische und präklinische PET/CT- Arbeiten zur Interaktion von TH und BAT vorstellen und iii) diese Arbeiten in Verbindung zu eigenen Studien im Rahmen des DFG-Schwerpunktprogramms thyroid trans act setzen.

Keywords

Thyroid hormone - brown adipose tissue - noradrenaline - PET/CT imaging

Schlüsselwörter

Schilddrüsenhormone - braunes Fettgewebe - Noradrenalin - PET/CT - Bildgebung

^* contributed equally

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