Priority Programme: THYROID TRANS ACT
Translation of Thyroid Hormone Actions beyond Classical Concepts

Hot Topic

White adipose tissue browning by thyroidal dysfunction

The article “Thyroid hormone status defines brown adipose tissue activity and browning of white adipose tissues in mice” has been awarded this year’s Novartis-Preis "Junge Endokrinologie" 2016. Dr. Kerstin Krause, the senior author of this study, summarizes the main statements.

Thyroid hormones (TH) are intimately involved in the regulation of energy metabolism. Under conditions of thermoneutrality, core body temperature can be maintained in the absence of any thermoregulatory process (e.g. shivering). However, under conditions of cold exposure adaptive thermogenesis occurs through a compensatory increase in sympathetic nervous system tone (SNS) which accelerates energy expenditure and increases body temperature. Additionally, SNS stimulation results in activation of β-adrenergic receptors by the release of norepinephrine which induces both the enhanced thermogenic activity of existing brown adipocytes tissue (BAT) and the recruitment of new cells to brown adipose depots. The important role of TH in the regulation of body temperature homeostasis is well understood with regard to cold or heat intolerance of animals and humans with hypothyroidism or hyperthyroidism. Moreover, there is preliminary evidence that suggests a role for TH in the induction of “beige” adipocytes in white adipose tissue “WAT”.

There is still limited understanding of whether and how different thyroid states, i.e. hypo- and hyperthyroidism, regulate BAT thermogenesis as well as the thermogenic activity of WAT. Therefore, the present study aimed to determine TH induced effects on (I) BAT activity and (II) WAT browning in a mouse model of thyroidal dysfunction with a view to incorporate the results into the context of TH-regulated effects on whole-body energy homeostasis.

Collectively, our data provide first evidence for differential mechanisms contributing to WAT browning dependent upon thyroidal state. This is most apparent in hypothyroid mice that exhibit increased adipogenesis and de-novo differentiation of brown adipocytes potentially as a compensatory mechanism to hypothermia resulting from BAT inactivity. In hyperthyroid mice, it can be hypothesized that increased β-adrenergic activation contributes to WAT browning. However, it has to be emphasized that with the current data we cannot exclude potential non cell-autonomous contributions from the SNS to adipose tissue browning irrespective of thyroidal state. Thus, in order to rule out that temperature as opposed to thyroidal state is the underlying reason for WAT browning, the findings of the present study need to be confirmed under temperatures where sympathetic stimulation of facultative thermogenesis is depressed i.e. thermoneutrality (30°C).

Back to the list