The relevance of thyroid hormones for the transdifferentiation of white into brown adipose tissue

• Applicant: Professorin Dr. Anke Tönjes
• Subject Area: Endocrinology, Diabetology, Metabolism
• Term: from 2012 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 221169610

There is a growing interest in brown adipocytes since it has been demonstrated that a notable amount brown adipose tissue (BAT) can be detected also in adults. The entire function and regulation of these cells and especially the origin has not been elucidated so far. Recently, BAT has become a potential target for pharmacological and genetic manipulation to treat human obesity since positron emission tomography (PET) has provided evidence that adult humans retain metabolically active BAT depots which can be induced in response to cold and sympathetic nervous system activation, particularly by the thyroid hormone (TH) T3. In contrast to effects on BAT activity, there are no data about the effect of T3 on the formation of new brown adipocytes. The aim of this study is I.) to investigate if there is an effect of thyroid hormone on BAT formation and II.) to clarify the origin of newly formed adipocytes occurring after T3 treatment. We will apply 1) an in-vitro model on primary murine precursor cells to investigate the adipocyte differentiation under TH treatment; 2) an in-vivo model on hypo- and hyperthyroid mice to dissect differences in morphological, functional and molecular parameters in WAT and BAT due to TH; 3) a human study focussing on the investigation of thyroid function and BAT activity using F18-FDG-PET/computed tomography (CT). Furthermore, we will investigate the differential gene expression of fat depots before and after L-thyroxin replacement/ thyreostatic treatment in apparent thyroid dysfunction. Perspectively, stimulating conversion of white into brown adipocytes through the influence of TH might be translated into an effective therapy to raise energy expenditure.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1629: THYROID TRANS ACT - Translation of Thyroid Hormone Actions beyond Classical Concepts
• Participating Persons: Professor Dr. Swen Hesse; Dr. Kerstin Krause