Pharmacological Activation of Thyroid Hormone Receptors Elicits a Functional Conversion of White to Brown Fat

•TR activation elicits a program of thermogenesis in subcutaneous white adipocytes•TR-mediated browning coincides with anti-obesogenic and anti-diabetic effects•TR-agonist-induced browning of white adipocytes is cell autonomous•TR-mediated browning dissociates activation of WAT from classical BAT

SummaryThe functional conversion of white adipose tissue (WAT) into a tissue with brown adipose tissue (BAT)-like activity, often referred to as “browning,” represents an intriguing strategy for combating obesity and metabolic disease. We demonstrate that thyroid hormone receptor (TR) activation by a synthetic agonist markedly induces a program of adaptive thermogenesis in subcutaneous WAT that coincides with a restoration of cold tolerance to cold-intolerant mice. Distinct from most other browning agents, pharmacological TR activation dissociates the browning of WAT from activation of classical BAT. TR agonism also induces the browning of white adipocytes in vitro, indicating that TR-mediated browning is cell autonomous. These data establish TR agonists as a class of browning agents, implicate the TRs in the browning of WAT, and suggest a profound pharmacological potential of this action.

Graphical AbstractFigure optionsDownload full-size imageDownload as PowerPoint slide