Direct PPARγ Activation by L-Thyroxin and TETRAC Links Thyroid Hormone and PPAR Signaling

Thyroid hormones (THs) operate numerous physiological processes through the nuclear thyroid hormone receptors and several other proteins. Here we report direct peroxisome proliferator-activated receptor gamma (PPARγ) and retinoid X receptor (RXR) activation by the T4 metabolite TETRAC at nanomolar affinity. We demonstrate that TETRAC is a highly active PPARγ agonist promoting PPARγ signaling in cell-free, cellular and in vivo settings suggesting that TETRAC and other THs are activators of PPARγ linking TH and PPAR signaling.